Zusammenfassung
Der vorliegende Artikel fasst die wesentlichen Aspekte des aktuellen Wissens um eosinophile Granulozyten zusammen, ordnet die Eosinophilie in die Dimensionen gesunde oder schädigende ...Reaktion ein, wirft einen besonderen Blick auf das Gebiet HNO-Heilkunde in Bezug auf Eosinophile und gibt Handlungsempfehlungen zur Diagnostik und therapeutischen Intervention bei einer nachgewiesenen Eosinophilie auch und insbesondere als unerwünschte Arzneimittelwirkung (UAW) unter medikamentöser Therapie. Die Gedanken sind angeregt durch Mitteilungen auf dem 29. Kongress der European Rhinologic Society in Sofia, Bulgarien, 2023.
This article summarizes the essential aspects of current knowledge about eosinophils, classifies eosinophilia in terms of the dimensions healthy or harmful reaction, takes a specific look at ...eosinophils in the field of otorhinolaryngology, and gives recommendations for diagnostic workup and therapeutic intervention in case of proven eosinophilia, particularly as an adverse drug reaction. The thoughts are inspired by communications at the 29th Congress of the European Rhinologic Society in Sofia, Bulgaria, 2023.
Post-COVID syndrome (PCS) is an important sequela of COVID-19, characterised by symptom persistence for >3 months, post-acute symptom development, and worsening of pre-existing comorbidities. The ...causes and public health impact of PCS are still unclear, not least for the lack of efficient means to assess the presence and severity of PCS.
COVIDOM is a population-based cohort study of polymerase chain reaction (PCR) confirmed cases of SARS-CoV-2 infection, recruited through public health authorities in three German regions (Kiel, Berlin, Würzburg) between November 15, 2020 and September 29, 2021. Main inclusion criteria were (i) a PCR confirmed SARS-CoV-2 infection and (ii) a period of at least 6 months between the infection and the visit to the COVIDOM study site. Other inclusion criteria were written informed consent and age ≥18 years. Key exclusion criterion was an acute reinfection with SARS-CoV-2. Study site visits included standardised interviews, in-depth examination, and biomaterial procurement. In sub-cohort Kiel-I, a PCS (severity) score was developed based upon 12 long-term symptom complexes. Two validation sub-cohorts (Würzburg/Berlin, Kiel-II) were used for PCS score replication and identification of clinically meaningful predictors. This study is registered at clinicaltrials.gov (NCT04679584) and at the German Registry for Clinical Studies (DRKS, DRKS00023742).
In Kiel-I (n = 667, 57% women), 90% of participants had received outpatient treatment for acute COVID-19. Neurological ailments (61·5%), fatigue (57·1%), and sleep disturbance (57·0%) were the most frequent persisting symptoms at 6–12 months after infection. Across sub-cohorts (Würzburg/Berlin, n = 316, 52% women; Kiel-II, n = 459, 56% women), higher PCS scores were associated with lower health-related quality of life (EQ-5D-5L-VAS/-index: r = -0·54/ -0·56, all p < 0·0001). Severe, moderate, and mild/no PCS according to the individual participant's PCS score occurred in 18·8%, 48·2%, and 32·9%, respectively, of the Kiel-I sub-cohort. In both validation sub-cohorts, statistically significant predictors of the PCS score included the intensity of acute phase symptoms and the level of personal resilience.
PCS severity can be quantified by an easy-to-use symptom-based score reflecting acute phase disease burden and general psychological predisposition. The PCS score thus holds promise to facilitate the clinical diagnosis of PCS, scientific studies of its natural course, and the development of therapeutic interventions.
The COVIDOM study is funded by the Network University Medicine (NUM) as part of the National Pandemic Cohort Network (NAPKON).
Anti-neutrophil cytoplasmic autoantibodies (ANCA) targeting proteinase 3 (PR3) and myeloperoxidase expressed by innate immune cells (neutrophils and monocytes) are salient diagnostic and pathogenic ...features of small vessel vasculitis, comprising granulomatosis with polyangiitis (GPA), microscopic polyangiitis, and eosinophilic GPA. Genetic studies suggest that ANCA-associated vasculitides (AAV) constitute separate diseases, which share common immunological and pathological features, but are otherwise heterogeneous. The successful therapeutic use of anti-CD20 antibodies emphasizes the prominent role of ANCA and possibly other autoantibodies in the pathogenesis of AAV. However, to elucidate causal effects in AAV, a better understanding of the complex interplay leading to the emergence of B lymphocytes that produce pathogenic ANCA remains a challenge. Different scenarios seem possible; e.g., the break of tolerance induced by a shift from non-pathogenic toward pathogenic autoantigen epitopes in inflamed tissue. This review gives a brief overview on current knowledge about genetic and epigenetic factors, barrier dysfunction and chronic non-resolving inflammation, necro-inflammatory auto-amplification of cellular death and inflammation, altered autoantigen presentation, alternative complement pathway activation, alterations within peripheral and inflamed tissue-residing T- and B-cell populations, ectopic lymphoid tissue neoformation, the characterization of PR3-specific T-cells, properties of ANCA, links between autoimmune disease and infection-triggered pathology, and animal models in AAV.
Objective
Goal of this study was to investigate, whether sialendoscopy in obstructive salivary gland disorders affects patients' oral health‐related quality of life compared to healthy individuals, ...and to determine factors that might influence this relationship.
Study design
Retrospective observational study.
Setting
University of Kiel, Department of Otorhinolaryngology, Head and Neck Surgery.
Subjects and methods
A group of 130 patients, undergoing sialendoscopy between 01/2004 and 06/2017 was considered. Oral health‐related quality of life was assessed using the OHIP‐G14 (Oral Health Impact Profile) in combination with a custom‐made questionnaire on satisfaction and success in relation to sialendoscopy.
Results
Oral health‐related quality of life of patients without dentures or with removable dentures was significantly worse than in the healthy population, whereas the necessity of multiple additional follow‐up treatments was associated with worse oral health‐related quality of life. No essential predisposing factors were identified. Average satisfaction with the intervention was observed to be x̅ = 4.33 (SD = 3.69) on a visual analogue scale from 1 (=very satisfied) to 10 (=very unsatisfied). A longer follow‐up period and a higher patients' age were positively related, whereas removal of salivary gland during follow‐up was negatively related to satisfaction. In 113 cases (86.9%) long‐term preservation was accomplished and 115 (88.5%) patients would repeat a sialendoscopy in case needed.
Conclusion
In summary, sialendoscopy resulted in long‐term high subjective and objective success rates. However, oral health‐related quality of life scores did not reach those levels found in the healthy population.
•Fist study analysing tissue, brushes and sputum for all patients also for viral mRNA.•HPV detection performed in brushes/sputum inconsistently reflect tissue HPV status.•In terms of virus activity, ...p16 seems insufficient to predict tissue HPV status.•E6-mRNA analysis detects active HPV infection in non-neoplastic tonsillar tissues.•Data gives rise to the question whether tonsillectomy might prevent TSCC.
Previous studies describe a correlation between HPV-positivity and non-smoking in TSCC; p16INK4A-expression as surrogate-marker for HPV-DNA/RNA-positivity is discussed controversially. In the present study, these parameters are assessed prospectively. HPV-status of sputum and tonsillar-swabs was analyzed to determine their validity as surrogate-marker for tissue-HPV-status.
TSCC- (n = 52) and non-neoplastic tonsillar tissue (n = 163) were analyzed. HPV-DNA- and HPV-RNA-status of total sputum, cellular fraction and supernatants, tonsillar-swabs and -tissue was determined by (RT)-PCR. Immunohistochemistry determined p16INK4A-expression.
23/163 (14.2%) non-neoplastic tonsils were HPV-DNA-positive; five patients (3 HPV16, 2 HPV11) had active HPV-infections (HPV-RNA-positive), in all biomaterials. 140/163 (85.9%) patients were either HPV-DNA-positive or HPV-DNA-negative in all samples. 21/52 (40.4%) TSCC-tonsils were HPV-DNA-positive; 17 patients were HPV-RNA-positive (14 HPV16; 4 HPV18). 40/52 (76.9%) TSCC-patients were congruent in all biomaterials. p16INK4A-expression alone would have misclassified the HPV-status of 14/52 (26.2%) TSCC-patients.
This prospective study confirms the discrepancy between HPV-status and p16INK4A-expression and the significant correlation between non-smoking and HPV-DNA-positivity. HPV-sputum- and/or swab-results do not consistently match tissue-results, possibly having (detrimental) consequences if those were used to assess tissue-HPV-status. In the 5 patients with active HPV infection in the non-neoplasitic tonsils, tonsillectomy likely prevented subsequent development of TSCC.
•Smoking is associated with an increased SLPI and AnxA2 expression in human mucosa with surplus of SLPI.•SLPI and HPV interact with AnxA2 with this interaction being pivotal for cell entry of ...HPV.•HPV-positive carcinomas are associated with non-smoking and low SLPI levels and HPV-negative carcinomas are associated with smoking and high SLPI levels.•The interaction between smoking, SLPI and AnxA2 expression may explain the interaction between smoking and HPV.
Six own studies confirm a correlation between smoking, expression of the secretory leukocyte protease inhibitor (SLPI, an antileukoproteinase) and expression of Annexin A2 (AnxA2), and their influence on human papilloma virus (HPV)-infections. SLPI and HPV are ligands of AnxA2.
This correlation was tested on 928 tissue samples from 892 patients in six independent studies squamous cell carcinoma of the head and neck (HNSCC), n = 522; non-neoplastic tonsils n = 214; clinically normal mucosa, n = 93 (of these n = 57 were obtained from patients treated for non-malignant diseases and n = 36 were obtained from HNSCC-patients) and vulvar squamous cell carcinoma (VSCC) n = 99. HPV-DNA-status was determined by GP5+/GP6+-PCR, followed in case of HPV-positivity by Sanger sequencing and RT-PCR using HPV-type specific primers. SLPI- and AnxA2-gene-expression was determined by RT-q-PCR; SLPI-protein-expression was additionally determined by immunohistochemistry (IHC); the data were correlated with each other and with patient characteristics.
Smoking results in increased SLPI-gene- and protein- and AnxA2-gene-expression with significantly higher SLPI- than AnxA2-gene-expression. SLPI is decreased in non-smokers with a continuous AnxA2-surplus. HPV-status correlates with smoking habit, with smokers being mostly HPV-negative and non-smokers HPV-positive.
We hypothesize that smoking leads to SLPI-overexpression with SLPI-binding to AnxA2. Thus, HPV cannot bind to AnxA2 but this seems pivotal for HPV-cell-entry. Smoking favors SLPI-expression resulting in HPV-negative carcinomas, while HPV-positive carcinomas are more common in non-smokers possibly due to a surplus of unbound AnxA2. In addition, the hypothesis may contribute to understand why smokers show increased oral HPV-prevalence in natural history studies but do not necessarily develop HPV-associated lesions.
Smoking has a negative impact on survival of HNSCC patients. In addition, smoking is associated with the prevalence of co-morbidities and, thus, it may be assumed that not smoking
but co-morbidities ...impact the course of therapy in terms of lower compliance and dose-reduction. However, data addressing this issue is sparse and conflicting at present, specifically for HNSCCs.
Patient files and tumor documentation from 643 consecutive cases of the University Head and Neck Cancer Centre Kiel were analyzed retrospectively. Patient characteristics and smoking habits were assessed and correlated with co-morbidities and course of treatment.
The examined 643 patient files showed that 113 (17.6%), 349 (54.3%), and 180 (28%) patients were never, active, and former smokers, respectively. Three hundred fifteen (49%) were treated by surgery only; 121 (18.8%) received surgery + adjuvant RCT and 72 (11.2%) surgery + adjuvant RT. 111 (17.3%) received primary RCT and 24 (3.7%) primary RT. 131 (20.4%) and 512 (79.6%) had no or had co-morbidities, respectively. Smoking (>10 py) was significantly associated with co-morbidities (
= 0.002). However, smoking and co-morbidities, neither alone nor in combination, were correlated with failure in reaching target doses of radio(chemo)therapy (
> 0.05). Applying (verified) Carlson-Comorbidity-Index (CCI) did not change the results.
As expected, smoking is significantly associated with co-morbidities. Dose-reduction of radio(chemo)therapy is as common among active smokers and patients with co-morbidities as among never smokers and patients without co-morbidities. Thus, smoking and co-morbidity seems to impact survival by other means than impairing planned therapy regimens.
Abstract
Introduction
Squamous cell Carcinoma of the Head and Neck (HNSCC) is the most common tumor entity of malignant processes in the head and neck area. Due to the metastasizing behavior of ...these tumors, the staging is indispensable for the treatment planning and requires imaging techniques, which are sensitive, specific, and as far as possible cost-effective, to benefit ultimately the patient and to ensure optimal care.
Objectives
The aim of the present study is to compare the clinical examination including palpation, ultrasound and computed tomography (CT)/magnetic resonance imaging (MRI) for the diagnosis of neck metastases to make the correct indication for a neck dissection.
Methods
Data from 286 patients with HNSCC were analyzed for neck metastases to determine which diagnostic tool is the best to answer the question if a neck dissection is necessary or not. Each study method was examined retrospectively by comparing sensitivity, specificity, the positive/negative predictive value, the positive likelihood ratio and the diagnostic accuracy.
Results
The ultrasound showed a sensitivity of 91.52%, a specificity of 61.67%, a positive/negative predictive value of 76.65%/84.09%, a positive likelihood ratio of 2.39 and a diagnostic accuracy of 78.95%. The clinical examination showed a sensitivity of 75.76%, a specificity of 66.12%, a positive/negative predictive value of 75.30%/66.67%, a positive likelihood ratio of 2.24 and a diagnostic accuracy of 71.68%. The CT/MRI showed a sensitivity of 78.66%, a specificity of 62.50%, a positive/negative predictive value of 74.14%/68.18%, a positive likelihood ratio of 2.10 and a diagnostic accuracy of 71.83%. Radiographically, ultrasound, as well as the clinical examination, could be judged to be free from radiation load and side effects from the contrast medium. The high dependence on the investigator when using ultrasound made reproducibility of the results difficult.
Conclusions
It could be shown that ultrasound was the diagnostic tool with the highest sensitivity, positive/negative predictive value, positive likelihood ratio and diagnostic accuracy by detecting and interpreting metastases in the head and neck region correctly. Whether a neck dissection should be performed depends to a large extent on the ultrasound findings.
Wegener's granulomatosis (WG) is characterized by granulomatous lesions and vasculitic disease manifestations. Granulomatous lesions are found in the upper and lower respiratory tract (eg, ...granulomatous sinusitis, orbital masses, and pulmonary granuloma), whereas vasculitic manifestations occur frequently in lung (alveolar hemorrhage) and kidney (glomerulonephritis). Vasculitis is typically associated with antineutrophil cytoplasmic antibodies (ANCA) directed against proteinase 3. WG has been traditionally associated with a poor outcome and increased mortality as documented by numerous studies; however, recent cohort studies report an improved outcome, probably a consequence of increased awareness leading to an earlier diagnosis, and to improved treatment strategies derived from evidence from controlled trials. Treatment regimens for WG, adapted to disease stage and activity, are reviewed and discussed in this article.
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