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BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a prevalent chronic inflammatory condition affecting the nose and paranasal sinuses, posing a significant socio-economic impact with substantial challenges in management. Biologics targeting type 2 inflammation such as dupilumab, have emerged as promising options. This study addresses a critical knowledge gap by comprehensively evaluating the 3-year impact of sustained dupilumab therapy in CRSwNP. METHODS: A multicentric, retrospective collection of real-world data from five tertiary referral centers in Germany was conducted, enrolling 150 adult patients. The study investigated patient-reported outcomes, disease-specific indices and clinical measures, focusing on therapeutic response persistence, adverse events, and factors influencing treatment continuity. RESULTS: Results indicate significant improvements in clinical parameters from baseline (n = 150) with sustained effectiveness after 36 months (n = 138) as indicated in mean score ± standard deviation. Dupilumab treatment significantly improved overall disease-related impairment (VAS score: 7.5 ± 2.5 to 1.6 ± 1.3) and rhinosinusitis symptoms (SNOT-22: 59.4 ± 19.4 to 18.0 ± 15.0). Nasal Polyp Scores (NPS) decreased (5.3 ± 1.8 to 0.7 ± 1.1), and olfactory function improved (3.2 ± 2.5 to 8.4 ± 2.8), with three out of four patients achieving normosmia or hyposmia after 36 months. An "Excellent" treatment response according to EUFOREA23 criteria was observed in 76.5% of patients after 36 months. Sixteen patients discontinued Dupilumab, 12 permanently. Adverse events totaled 69 in 48 patients, commonly self-limiting. CONCLUSION: The study highlights the enduring effectiveness and lack of habituation to dupilumab after a sustained therapy of 3 years, providing valuable insights into its long-term therapeutic implications for CRSwNP patients.
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BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a type2 inflammatory disease of the upper airways, with severe impairment of quality of life. Persons affected by NSAID-exacerbated respiratory disease (NERD) usually present with highly dynamic recurrence of polyps and disease despite prior treatment with sinus surgeries, oral corticosteroids, and aspirin desensitization (ATAD). Biologic therapy has fundamentally changed the choice of therapeutic concept; however, limited data exist on subgroups such as NERD patients. The aim of the current article is to report on a multicenter retrospective study on add-on therapy with dupilumab, omalizumab, and mepolizumab in patients with NERD. METHODS: This is a retrospective cohort study of patients (NERD+, status after ATAD) in three reference centers in Germany (Munich, Mainz, Berlin). Subjective and objective parameters were collected at 4, 8, and 12 months after biologic therapy initiation in accordance with current EPOS/EUFOREA (European Position Paper on Rhinosinusitis and Nasal Polyps/European Forum for Research and Education in Allergy and Airway Diseases) guidelines. Biologic agents were chosen depending on availability and patient characteristics. RESULTS: Treatment was commenced in 122 patients meeting the criteria for CRSwNP and NERD. The endoscopic polyp score, SNOT-22 questionnaire score, visual analogue scoring of total symptoms/severity of disease, and sense of smell (psychophysical testing with Sniffin'Sticks/Brief Smell Identification Test, BSIT; Sensonics, Inc., Haddon Heights, NJ, USA) improved significantly after 4 and 12 months of add-on therapy (pâ¯< 0.0001). All three biologic agents significantly improved one or more disease parameter. Adverse events were not life threatening but led to change of biologic agent in 4 cases. Patients rated biologic therapy significantly better than ATAD, with improved long-term disease control. CONCLUSION: Add-on biologic therapy is effective, safe, and widely accepted among CRSwNPâ¯+ NERD patients. Future studies might allow for personalized algorithms with sequential surgery, ATAD, and/or biologic therapy.
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Anti-Inflamatórios não Esteroides , Aspirina , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Anti-Inflamatórios não Esteroides/efeitos adversos , Anti-Inflamatórios não Esteroides/uso terapêutico , Alemanha , Estudos Retrospectivos , Aspirina/efeitos adversos , Resultado do Tratamento , Dessensibilização Imunológica/métodos , Sinusite/induzido quimicamente , Sinusite/tratamento farmacológico , Sinusite/terapia , Adulto , Pólipos Nasais/tratamento farmacológico , Asma Induzida por Aspirina/terapia , Asma Induzida por Aspirina/diagnóstico , Anticorpos Monoclonais Humanizados/efeitos adversos , Anticorpos Monoclonais Humanizados/uso terapêutico , Terapia Biológica/métodos , Terapia Biológica/efeitos adversos , Rinite/induzido quimicamente , Rinite/terapia , Omalizumab/uso terapêutico , Omalizumab/efeitos adversos , Estudos de Coortes , Idoso , Doença CrônicaRESUMO
BACKGROUND: With targeted inhibition of type 2 inflammation, biologics represent the standard add-on therapy for inadequately controlled severe forms of chronic rhinosinusitis with nasal polyps (CRSwNP). Despite standardization with paper-based checklists, the documentation of medical history and current findings pertinent to indication criteria are a significant challenge for physicians. Through development of an application based on structured reporting, the current study aimed to improve documentation quality and simplify the decision-making process. Previously available paper checklists served as a comparison. METHODS: For this study, a digital incremental tool was programmed to record current findings and check for fulfilment of indication criteria. The tool was compared with other checklists in terms of completeness, time required, and readability. RESULTS: A total of 20 findings were collected for each of the three documentation options and included in the analysis. Documentation with the two paper-based checklists had comparable information content: 17.5⯱ 5.1/21.7⯱ 7.6 points out of a maximum of 43 points; pâ¯> 0.05. Documentation using the digital application led to a significant increase in information content compared to all paper-based documentation. The average score was 38.25⯱ 3.7 (88.9% of maximum; pâ¯< 0.001). On average, user satisfaction was high (9.6/10). Use of the digital application was initially more time consuming, but as more cases were documented, the time taken improved significantly. CONCLUSION: In the future, structured reporting using apps could replace paper-based reporting for the indication of biologic therapy in CRSwNP patients and offer additional benefits in terms of data quality and traceability of results. The increasing volume of documentation in the future, the progress of digitalization, and the possibility of networking between individual centers make introduction of the app in the near future both likely and economical.
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Working during pregnancy and breastfeeding is a special situation for both the employee and the employer/supervisor. The amended version of the Maternity Protection Act (MuSchG), which came into force on January 1st, 2018, protects the health of women and their children while working, training or studying during pregnancy, after giving birth and while breastfeeding. Women should be able to continue their employment or related activities during this time without jeopardising their health or that of their child. This law was furthermore reformed to prevent discrimination against the working mother during this time. In order to create the best and safest possible framework conditions for employment during pregnancy and breastfeeding, the DGHNO-KHC and the BVHNO would like to present a "general positive list" and a "positive list for surgical activities" as part of this statement, which should serve as a guideline for all relevant parties. This agreed positive list is intended to enable pregnant and breastfeeding doctors to carry out patient-related activities as well as head and neck surgeries in accordance with the MuSchG of 2018. Hereby, affected colleagues should have the opportunity to continue working self-determined.
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Vitamin D (VitD) and its receptor (VDR) have been intensively investigated in many cancers. As knowledge for head and neck cancer (HNC) is limited, we investigated the (pre)clinical and therapeutic relevance of the VDR/VitD-axis. We found that VDR was differentially expressed in HNC tumors, correlating to the patients' clinical parameters. Poorly differentiated tumors showed high VDR and Ki67 expression, whereas the VDR and Ki67 levels decreased from moderate to well-differentiated tumors. The VitD serum levels were lowest in patients with poorly differentiated cancers (4.1 ± 0.5 ng/mL), increasing from moderate (7.3 ± 4.3 ng/mL) to well-differentiated (13.2 ± 3.4 ng/mL) tumors. Notably, females showed higher VitD insufficiency compared to males, correlating with poor differentiation of the tumor. To mechanistically uncover VDR/VitD's pathophysiological relevance, we demonstrated that VitD induced VDR nuclear-translocation (VitD < 100 nM) in HNC cells. RNA sequencing and heat map analysis showed that various nuclear receptors were differentially expressed in cisplatin-resistant versus sensitive HNC cells including VDR and the VDR interaction partner retinoic acid receptor (RXR). However, RXR expression was not significantly correlated with the clinical parameters, and cotreatment with its ligand, retinoic acid, did not enhance the killing by cisplatin. Moreover, the Chou-Talalay algorithm uncovered that VitD/cisplatin combinations synergistically killed tumor cells (VitD < 100 nM) and also inhibited the PI3K/Akt/mTOR pathway. Importantly, these findings were confirmed in 3D-tumor-spheroid models mimicking the patients' tumor microarchitecture. Here, VitD already affected the 3D-tumor-spheroid formation, which was not seen in the 2D-cultures. We conclude that novel VDR/VitD-targeted drug combinations and nuclear receptors should also be intensely explored for HNC. Gender-specific VDR/VitD-effects may be correlated to socioeconomic differences and need to be considered during VitD (supplementation)-therapies.
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Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Terapia de Alvo Molecular , Receptores de Calcitriol , Vitamina D , Vitaminas , Feminino , Humanos , Masculino , Carcinoma de Células Escamosas/tratamento farmacológico , Cisplatino/uso terapêutico , Antígeno Ki-67/metabolismo , Ligantes , Fosfatidilinositol 3-Quinases/metabolismo , Receptores de Calcitriol/metabolismo , Vitamina D/uso terapêutico , Vitaminas/uso terapêutico , Neoplasias de Cabeça e Pescoço/tratamento farmacológicoRESUMO
BACKGROUND: Olfactory dysfunction is one of the leading symptoms of COVID-19. Previous data suggest a different prevalence between the wild type virus and its subsequent variants. Here, we report on a prospective study to psychophysically compare olfactory function in acute SARS-CoV-2 infection between wild type, VOC alpha and VOC delta. METHODS: SARS-CoV-2 was confirmed by reverse-transcription quantitative real-time PCR and virus variants were differentiated by high-sensitive next-generation sequencing. Home-quarantined were sent a validated and blinded smell identification test. A detailed instruction ensured correct self-administration. RESULTS: A total of 125 patients were included in study. Patients with the wild type of SARS-CoV-2 self-evaluated their olfactory function significant lower on the visual analog score compared patients with the VOCs alpha or delta (4.1 ± 1.5 vs. 6.8 ± 2.9 and 7.3 ± 0.9; p < 0.001). Likewise, a significant difference of the prevalence of psychophysically confirmed hyposmia (wild type: 73%; alpha: 41%; delta 48%; p < 0.01) and smell test score (48 ± 25% vs. 70 ± 23% and 67 ± 18%; p < 0.01) could be seen between wild type on one side and VOCs alpha and delta on the other side. CONCLUSION: In this study, both self-reports and psychophysical testing revealed a significant higher prevalence of olfactory impairment in the wild type of SARS-CoV-2 compared to the VOCs alpha and delta.
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COVID-19 , Transtornos do Olfato , COVID-19/epidemiologia , Humanos , Transtornos do Olfato/diagnóstico , Transtornos do Olfato/epidemiologia , Prevalência , Estudos Prospectivos , SARS-CoV-2/genética , OlfatoRESUMO
BACKGROUND: Chronic rhinosinusitis is regarded as a chronic airway disease. According to WHO recommendations, it may be a risk factor for COVID-19 patients. In most CRSwNP cases, the inflammatory changes affecting the nasal and paranasal mucous membranes are type-2 (T2) inflammation endotypes. METHODS: The current knowledge on COVID-19 and on treatment options for CRS was analyzed by a literature search in Medline, Pubmed, international guidelines, the Cochrane Library and the Internet. RESULTS: Based on international literature, on current recommendations by WHO and other international organizations as well as on previous experience, a panel of experts from EAACI and ARIA provided recommendations for the treatment of CRS during the COVID-19 pandemic. CONCLUSION: Intranasal corticosteroids remain the standard treatment for CRS in patients with SARS-CoV-2 infection. Surgical treatments should be reduced to a minimum and surgery preserved for patients with local complications and for those with no other treatment options. Systemic corticosteroids should be avoided. Treatment with biologics can be continued with careful monitoring in noninfected patients and should be temporarily interrupted during the course of the COVID-19 infection.
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COVID-19/epidemiologia , Rinite/tratamento farmacológico , SARS-CoV-2 , Sinusite/tratamento farmacológico , Corticosteroides/administração & dosagem , Asma/tratamento farmacológico , Produtos Biológicos/uso terapêutico , Doença Crônica , Humanos , Pólipos Nasais/tratamento farmacológicoRESUMO
BACKGROUND: Although there are many asymptomatic patients, one of the problems of COVID-19 is early recognition of the disease. COVID-19 symptoms are polymorphic and may include upper respiratory symptoms. However, COVID-19 symptoms may be mistaken with the common cold or allergic rhinitis. An ARIA-EAACI study group attempted to differentiate upper respiratory symptoms between the three diseases. METHODS: A modified Delphi process was used. The ARIA members who were seeing COVID-19 patients were asked to fill in a questionnaire on the upper airway symptoms of COVID-19, common cold and allergic rhinitis. RESULTS: Among the 192 ARIA members who were invited to respond to the questionnaire, 89 responded and 87 questionnaires were analysed. The consensus was then reported. A two-way ANOVA revealed significant differences in the symptom intensity between the three diseases (p < .001). CONCLUSIONS: This modified Delphi approach enabled the differentiation of upper respiratory symptoms between COVID-19, the common cold and allergic rhinitis. An electronic algorithm will be devised using the questionnaire.
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Asma , COVID-19 , Resfriado Comum , Rinite Alérgica , Consenso , Humanos , Rinite Alérgica/diagnóstico , SARS-CoV-2RESUMO
BACKGROUND: Reprocessing of complex instruments like flexible ENT-endoscopes with and without working channel are challanging for clinics and private practices. Aim of the study was to analyse the costs of an examination with a reusable endoscope-system and to compare it with two single-use endoscope-systems. MATERIAL AND METHODS: A cost minimization analysis was performed at the Department of Otorhinolaryngology, Head and Neck Surgery of the University Medical Center in Mainz, Germany. The local reusable endoscopy-system was compared with two single-use endoscopy-systems of Ambu and Karl Storz. RESULTS: Overall costs per examination with a reusable-scope were 23.03â (11.60â investment costs +â5.09â repair costs + 6.34â reprocessing costs). The single-use Endoscopy-system of Ambu resulted in 120.43â per examination (120.00â acquisition costs +â0.43â storage costs). Overall costs for the single-use endoscopy-system of Karl Storz were 223.44â per examination (investment costs for monitors 3.01â +â220.00â acquisition costs +â0.43â storage costs). DISCUSSION: Flexible single-use ENT-endoscopy-systems generate higher costs in comparison to conventional reusable ones. But there are also advantages from the medical and economical side. CONCLUSION: A smart mix of reusable and single-use endoscopy systems seems therefore usefull.
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Endoscópios , Endoscopia , Análise Custo-Benefício , Custos e Análise de Custo , Alemanha , HumanosRESUMO
BACKGROUND: Reports of head and neck ultrasound examinations are frequently written by hand as free texts. Naturally, quality and structure of free text reports is variable, depending on the examiner's individual level of experience. Aim of the present study was to compare the quality of free text reports (FTR) and structured reports (SR) of head and neck ultrasound examinations. METHODS: Both standard FTRs and SRs of head and neck ultrasound examinations of 43 patients were acquired by nine independent examiners with comparable levels of experience. A template for structured reporting of head and neck ultrasound examinations was created using a web-based approach. FTRs and SRs were evaluated with regard to overall quality, completeness, required time to completion, and readability by four independent raters with different specializations (Paired Wilcoxon test, 95% CI) and inter-rater reliability was assessed (Fleiss' kappa). A questionnaire was used to compare FTRs vs. SRs with respect to user satisfaction (Mann-Whitney U test, 95% CI). RESULTS: By comparison, completeness scores of SRs were significantly higher than FTRs' completeness scores (94.4% vs. 45.6%, p < 0.001), and pathologies were described in more detail (91.1% vs. 54.5%, p < 0.001). Readability was significantly higher in all SRs when compared to FTRs (100% vs. 47.1%, p < 0.001). The mean time to complete a report, however, was significantly higher in SRs (176.5 vs. 107.3 s, p < 0.001). SRs achieved significantly higher user satisfaction ratings (VAS 8.87 vs. 1.41, p < 0.001) and a very high inter-rater reliability (Fleiss' kappa 0.92). CONCLUSIONS: As compared to FTRs, SRs of head and neck ultrasound examinations are more comprehensive and easier to understand. On the balance, the additional time needed for completing a SR is negligible. Also, SRs yield high inter-rater reliability and may be used for high-quality scientific data analyses.
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Cabeça/diagnóstico por imagem , Pescoço/diagnóstico por imagem , Projetos de Pesquisa/normas , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Prontuários Médicos/normas , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Inquéritos e Questionários , Ultrassonografia , Adulto JovemRESUMO
We present a new method for the form measurement of optical surfaces using the spatial coherence function, which enables a shearing interferometer in combination with an LED multispot illumination to function as a measurement device. A new evaluation approach connects the measured data with the surface form by inverse raytracing. First measurement results with the inverse evaluation procedures are shown. We present the whole measurement in combination with the evaluation procedure. In addition, the convergence and stability of the implemented optimization task is investigated.
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OBJECTIVE: Lymph node ratio (LNR) was shown to be a prognostic factor in laryngeal and oral cavity primaries. The purpose of this study was to investigate the impact of the lymph node ratio in oropharyngeal squamous cell carcinoma (OPSCC) with a high incidence of HPV-related disease. Therefore, the role of LNR was evaluated as an additional predictive parameter to the 8th edition of AJCC TNM staging system. METHODS: From December 2009 to August 2015, patients diagnosed with primary oropharyngeal squamous cell carcinoma were prospectively enrolled. After tumor resection with uni- or bilateral neck dissection, patients with ≥ 1 nodal metastasis (pN+) were eligible for a retrospective LNR analysis. RESULTS: 137 patients underwent tumor resection with uni- or bilateral neck dissection. The proportion of HPV-associated disease was 42%. Most patients (n = 96; 70%) presented with involved neck nodes. In p16-positive OPSCC, the rate of pN + cases was significantly increased compared to p16-negative OPSCC (86% vs. 58%, p = 0.007). Patients with LNR ≤ 10% had a significant better overall survival (OS) and disease-specific survival (DSS). However, when stratified for p16-status, LNR ≤ 10% had a significant impact on OS only for HPV-associated tumors (p = 0.027), whereas LNR of ≤ 10% was not a significant predictor for better OS in p16-negative OPSCC (p = 0.143). CONCLUSION: The LNR with a cut-off value of 10% serves as an additional prognostic parameter in HPV-related OPSCC and may help to improve risk stratification in combination with the revised AJCC 8th edition TNM classification.
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Carcinoma de Células Escamosas/patologia , Linfonodos/patologia , Estadiamento de Neoplasias/métodos , Neoplasias Orofaríngeas/patologia , Infecções por Papillomavirus/complicações , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/cirurgia , Carcinoma de Células Escamosas/virologia , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Pescoço/patologia , Esvaziamento Cervical , Neoplasias Orofaríngeas/mortalidade , Neoplasias Orofaríngeas/cirurgia , Neoplasias Orofaríngeas/virologia , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Análise de SobrevidaRESUMO
In this publication, we demonstrate that recording the mutual intensity, instead of a wavefront, enables interferometric measurements with multiple independent light sources at the same time. This scheme can, for example, be used to overcome the problem of a limited acceptance angle of imaging systems in interferometry. We further show that, for a finite number of light sources, measuring a subspace of the mutual intensity equals the recording of the corresponding light field, which is sparse in phase space. This recording modality offers more flexibility with respect to the trade-off between angular multiplexing and spatial resolution than the state of the art, because it is not restricted by the geometric properties of a microlens array, but rather allows arbitrary sampling of the light field.
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COVID-19 , Transtornos do Olfato , Humanos , Transtornos do Olfato/etiologia , SARS-CoV-2 , OlfatoAssuntos
COVID-19/complicações , Transtornos do Olfato/diagnóstico , SARS-CoV-2 , Telemedicina , Adulto , Feminino , Humanos , MasculinoRESUMO
AKI involves early Toll-like receptor (TLR)-driven immunopathology, and resolution of inflammation is needed for rapid regeneration of injured tubule cells. Notably, activation of TLRs also has been implicated in epithelial repair. We hypothesized that TLR signaling drives tubule regeneration after acute injury through the induction of certain ILs. Systematic screening in vitro identified IL-22 as a candidate proregeneratory factor in primary tubular cell recovery, and IL-22 deficiency or IL-22 blockade impaired post-ischemic tubular recovery after AKI in mice. Interstitial mononuclear cells, such as dendritic cells and macrophages, were the predominant source of IL-22 secretion, whereas IL-22 receptor was expressed by tubular epithelial cells exclusively. Depleting IL-22-producing cells during the healing phase impaired epithelial recovery, which could be rescued entirely by reconstituting mice with IL-22. In vitro, necrotic tubular cells and oxidative stress induced IL-22 secretion selectively through TLR4. Although TLR4 blockade during the early injury phase prevented tubular necrosis and AKI, TLR4 blockade during the healing phase suppressed IL-22 production and impaired kidney regeneration. Taken together, these results suggest that necrotic cell-derived TLR4 agonists activate intrarenal mononuclear cells to secrete IL-22, which accelerates tubular regeneration and recovery in AKI.