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1.
Artigo em Inglês | MEDLINE | ID: mdl-39427271

RESUMO

BACKGROUND: From a healthcare professional's perspective, the use of ChatGPT (Open AI), a large language model (LLM), offers huge potential as a practical and economic digital assistant. However, ChatGPT has not yet been evaluated for the interpretation of polysomnographic results in patients with suspected obstructive sleep apnea (OSA). AIMS/OBJECTIVES: To evaluate the agreement of polysomnographic result interpretation between ChatGPT-4o and a board-certified sleep physician and to shed light into the role of ChatGPT-4o in the field of medical decision-making in sleep medicine. MATERIAL AND METHODS: For this proof-of-concept study, 40 comprehensive patient profiles were designed, which represent a broad and typical spectrum of cases, ensuring a balanced distribution of demographics and clinical characteristics. After various prompts were tested, one prompt was used for initial diagnosis of OSA and a further for patients with positive airway pressure (PAP) therapy intolerance. Each polysomnographic result was independently evaluated by ChatGPT-4o and a board-certified sleep physician. Diagnosis and therapy suggestions were analyzed for agreement. RESULTS: ChatGPT-4o and the sleep physician showed 97% (29/30) concordance in the diagnosis of the simple cases. For the same cases the two assessment instances unveiled 100% (30/30) concordance regarding therapy suggestions. For cases with intolerance of treatment with positive airway pressure (PAP) ChatGPT-4o and the sleep physician revealed 70% (7/10) concordance in the diagnosis and 44% (22/50) concordance for therapy suggestions. CONCLUSION AND SIGNIFICANCE: Precise prompting improves the output of ChatGPT-4o and provides sleep physician-like polysomnographic result interpretation. Although ChatGPT shows some shortcomings in offering treatment advice, our results provide evidence for AI assisted automation and economization of polysomnographic interpretation by LLMs. Further research should explore data protection issues and demonstrate reproducibility with real patient data on a larger scale.

2.
Laryngorhinootologie ; 103(9): 646-654, 2024 Sep.
Artigo em Alemão | MEDLINE | ID: mdl-38565182

RESUMO

INTRODUCTION: With a prevalence of 0.55% to 4%, chronic rhinosinusitis with nasal polyps (CRSwNP) is a relevant part of the daily work of German otolaryngologists. The aim of the questionnaire-based data collection was to assess the current treatment status of CRSwNP in Germany. MATERIAL AND METHODS: For this purpose, 24 questions within an anonymized online questionnaire were sent to all German ENT departments. RESULTS: Of 160 contacted ENT departments, 50 participated in the survey (31.3%). Among these, 76% performed more than 100 sinus surgeries annually and 38% treated more than 50 patients with biologics. Saline irrigations (80%) and intranasal glucocorticoids (GCS, 96%) were the most common conservative therapies. Systemic GCSs (52%) and intranasal GCS irrigation (20%) were less common. 80% of departments used biologics in the therapy of CRSwNP with an overall preference for dupilumab (70%). For therapy of aspirin intolerance, biologics (52%) were preferred to aspirin desensitization (26%). Prior to treatment with biologics clinical workup included the nasal polyp score (90%), the SNOT-22 questionnaire (84%), surrogate markers of type 2 inflammation (60%-72%), and computer tomography (50%). Final treatment success was assessed after 24 weeks (50%). CONCLUSION: Mostly, the responding departments followed German and European recommendations for diagnosis and therapy of CRSwNP. Therapy with biologics is widely used. The value of preoperative systemic GCS and the frequent performance of CT before initiation of therapy with a biologic should be debated in regard to its currently widespread use.


Assuntos
Glucocorticoides , Pólipos Nasais , Rinite , Sinusite , Pólipos Nasais/terapia , Pólipos Nasais/epidemiologia , Sinusite/terapia , Sinusite/epidemiologia , Sinusite/diagnóstico , Rinite/terapia , Rinite/epidemiologia , Rinite/diagnóstico , Doença Crônica , Alemanha , Humanos , Inquéritos e Questionários , Glucocorticoides/uso terapêutico , Padrões de Prática Médica/estatística & dados numéricos , Produtos Biológicos/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Pesquisas sobre Atenção à Saúde , Rinossinusite
3.
Clin Exp Allergy ; 52(6): 760-773, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35353925

RESUMO

BACKGROUND: The progression of chronic destructive lung disease in patients with humoral immunodeficiency (ID) and concomitant development of bronchiectasis is difficult to prevent. Lung function tests in these patients typically show bronchial obstruction of the small airways in combination with increased air trapping in the distal airways, which is consistent with small airway dysfunction. OBJECTIVE: The objective was to assess the grade of chronic lower airway inflammation and small airway dysfunction from induced sputum and the corresponding local pro-inflammatory mediator pattern to discriminate patients affected by bronchiectasis-related Small Airway Dysfunction (SAD). METHODS: In a prospective design, 22 patients with ID (14 CVID, 3 XLA, 3 hyper-IgM syndrome, 1 hyper-IgE syndrome and low IgG levels due to treatment with rituximab and 1 SCID after BMT and persistent humoral defect) and 21 healthy controls were examined. Lung function, Fraction Expiratory Nitric Oxide (FeNO) and pro-inflammatory cytokine levels were compared in subsets of patients with (ID + BE) and without bronchiectasis (ID) pre-stratified using high-resolution computed tomography (HRCT) scans and control subjects. RESULTS: Analysis of induced sputum showed significantly increased total cell counts and severe neutrophilic inflammation in ID. The concomitant SAD revealed higher total cell numbers compared to ID. Bronchial inflammation in ID is clearly mirrored by pro-inflammatory mediators IL-1ß, IL-6 and CXCL-8, whilst TNF-α revealed a correlation with lung function parameters altered in the context of bronchiectasis-related Small Airway Dysfunction. CONCLUSIONS: In spite of immunoglobulin substitution, bronchial inflammation was dominated by neutrophils and was highly increased in patients with ID + BE. Notably, the pro-inflammatory cytokines in patients with ID were significantly increased in induced sputum. The context-dependent cytokine pattern in relation to the presence of concomitant bronchiectasis associated with SAD in ID patients could be helpful in delimiting ID patient subgroups and individualizing therapeutic approaches.


Assuntos
Bronquiectasia , Biomarcadores , Brônquios , Bronquiectasia/complicações , Bronquiectasia/diagnóstico , Citocinas , Humanos , Inflamação , Estudos Prospectivos , Escarro
4.
Laryngorhinootologie ; 100(5): 382-392, 2021 05.
Artigo em Alemão | MEDLINE | ID: mdl-32698200

RESUMO

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 23.03 € (11.60 € investment costs + 5.09 € repair costs + 6.34 € reprocessing costs). The single-use Endoscopy-system of Ambu resulted in 120.43 € per examination (120.00 € acquisition costs + 0.43 € storage costs). Overall costs for the single-use endoscopy-system of Karl Storz were 223.44 € per examination (investment costs for monitors 3.01 € + 220.00 € acquisition costs + 0.43 € 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.


Assuntos
Endoscópios , Endoscopia , Análise Custo-Benefício , Custos e Análise de Custo , Alemanha , Humanos
5.
Pediatr Allergy Immunol ; 31(2): 143-149, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31660641

RESUMO

BACKGROUND: Bronchial allergen provocation (BAP) is an established tool for the diagnosis of allergy in patients with asthma, but its use is limited by the potential risk of severe asthmatic reactions. Nasal provocation testing (NPT) may be an alternative safe method and does not require sophisticated equipment. OBJECTIVE: The aim of this prospective study was to evaluate the concordance of both methods in patients with asthma and house dust mite (HDM) sensitization. METHODS: A total of 112 patients with HDM sensitization underwent BAP and had the following parameters analysed: decrease in FEV1, exhaled NO, and total and specific IgE. Within 12 weeks, NPT with HDM was performed in 74 patients with a median age of 9 years (range, 5-16 years). The results were evaluated using the Lebel score which quantifies major symptoms like rhinorrhea, nasal obstruction, sneezes and minor symptoms, such as pruritus, conjunctivitis and pharyngitis. RESULTS: Fifty-seven of 74 patients had an early asthmatic reaction, of which 41 were identified using the Lebel score. The Lebel score had a sensitivity of 71.9% and a positive predictive value (PPV) of 89.1%. In addition, an eNO ≥ 10 ppb (AUC 0.78), a specific IgE Dermatophagoïdes pteronyssinus ≥ 25.6 kU/L (AUC 0.76) and a specific IgE Dermatophagoïdes farinae ≥ 6.6 kU/L (AUC 0.78) were good predictors of an early asthmatic reaction. CONCLUSION: A sequential use of NPT prior to BAP is justified to establish the relevance of HDM allergy. In patients with a negative NPT, BAP is still recommended to rule out a HDM-induced asthmatic reaction.


Assuntos
Asma/diagnóstico , Testes de Provocação Brônquica/métodos , Hipersensibilidade/diagnóstico , Testes de Provocação Nasal/métodos , Adolescente , Animais , Antígenos de Dermatophagoides/imunologia , Criança , Feminino , Humanos , Imunização , Imunoglobulina E/metabolismo , Masculino , Estudos Prospectivos , Pyroglyphidae
6.
Eur Arch Otorhinolaryngol ; 277(1): 269-276, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31612337

RESUMO

PURPOSE: Free text reports (FTR) of head and neck ultrasound studies are currently deployed in most departments. Because of a lack of composition and language, these reports vary greatly in terms of quality and reliability. This may impair the learning process during residency. The purpose of the study was to analyze the longitudinal effects of using structured reports (SR) of head and neck ultrasound studies during residency. METHODS: Attending residents (n = 24) of a tripartite course on head and neck ultrasound, accredited by the German Society for Ultrasound in Medicine (DEGUM), were randomly allocated to pictures of common diseases. Both SRs and FTRs were compiled. All reports were analyzed concerning completeness, acquired time and legibility. Overall user contentment was evaluated by a questionnaire. RESULTS: SRs achieved significantly higher ratings regarding completeness (95.6% vs. 26.4%, p < 0.001), description of pathologies (72.2% vs. 58.9%, p < 0.001) and legibility (100% vs. 52.4%, p < 0.001) with a very high inter-rater reliability (Fleiss' kappa 0.9). Reports were finalized significantly faster (99.1 s vs. 115.0 s, p < 0.001) and user contentment was significantly better when using SRs (8.3 vs. 6.3, p < 0.001). In particular, only SRs showed a longitudinally increasing time efficiency (- 20.1 s, p = 0.036) while maintaining consistent completeness ratings. CONCLUSIONS: The use of SRs of head and neck ultrasound studies results in an increased longitudinal time-efficiency while upholding the report quality at the same time. This may indicate an additive learning effect of structured reporting. Superior outcomes in terms of comprehensiveness, legibility and time-efficiency can be observed immediately after implementation.


Assuntos
Neoplasias de Cabeça e Pescoço/diagnóstico por imagem , Internato e Residência/normas , Prontuários Médicos/normas , Ultrassonografia/normas , Adulto , Documentação/normas , Feminino , Controle de Formulários e Registros/normas , Cabeça/diagnóstico por imagem , Humanos , Masculino , Pescoço/diagnóstico por imagem , Sistemas de Informação em Radiologia/normas , Reprodutibilidade dos Testes , Inquéritos e Questionários
7.
Int J Mol Sci ; 21(20)2020 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-33066403

RESUMO

The effective management of tissue integration and immunological responses to transplants decisively co-determines the success of soft and hard tissue reconstruction. The aim of this in vivo study was to evaluate the eligibility of extracorporeal shock wave therapy (ESWT) with respect to its ability to modulate angiogenesis and immune response to a collagen matrix (CM) for tissue engineering in the chorioallantoic membrane (CAM) assay, which is performed with fertilized chicken eggs. CM were placed on the CAM on embryonic development day (EDD) 7; at EDD-10, ESWT was conducted at 0.12 mJ/mm2 with 500 impulses each. One and four days later, angiogenesis represented by vascularized area, vessel density, and vessel junctions as well as HIF-1α and VEGF gene expression were evaluated. Furthermore, immune response (iNOS2, MMP-9, and MMP-13 via qPCR) was assessed and compared between ESWT- and non-ESWT-groups. At EDD-14, the vascularized area (+115% vs. +26%) and the increase in vessel junctions (+751% vs. +363%) were significantly higher in the ESWT-group. ESWT significantly increased MMP-9 gene expression at EDD-11 and significantly decreased MMP-13 gene expression at EDD-14 as compared to the controls. Using the CAM assay, an enhanced angiogenesis and neovascularization in CM after ESWT were observed. Furthermore, ESWT could reduce the inflammatory activity after a latency of four days.


Assuntos
Colágeno/imunologia , Tratamento por Ondas de Choque Extracorpóreas/métodos , Neovascularização Fisiológica , Engenharia Tecidual/métodos , Animais , Proteínas Aviárias/genética , Proteínas Aviárias/metabolismo , Embrião de Galinha , Membrana Corioalantoide/irrigação sanguínea , Membrana Corioalantoide/imunologia , Colágeno/química , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Metaloproteinases da Matriz/genética , Metaloproteinases da Matriz/metabolismo , Óxido Nítrico Sintase Tipo II/genética , Óxido Nítrico Sintase Tipo II/metabolismo , Alicerces Teciduais/efeitos adversos , Alicerces Teciduais/química , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo
8.
BMC Med Imaging ; 19(1): 25, 2019 03 27.
Artigo em Inglês | MEDLINE | ID: mdl-30917796

RESUMO

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.


Assuntos
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 Jovem
9.
BMC Med Educ ; 19(1): 102, 2019 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-30971248

RESUMO

BACKGROUND: Reports of head and neck ultrasound examinations are frequently written by hand as free texts. This is a serious obstacle to the learning process of the modality due to a missing report structure and terminology. Therefore, there is a great inter-observer variability in overall report quality. Aim of the present study was to evaluate the impact of structured reporting on the learning process as indicated by the overall report quality of head and neck ultrasound examinations within medical school education. METHODS: Following an immersion course on head and neck ultrasound, previously documented images of three common pathologies were handed out to 58 medical students who asked to create both standard free text reports (FTR) and structured reports (SR). 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 two independent raters (Paired Wilcoxon test, 95% CI). Ratings were assessed for inter-rater reliability (Fleiss' kappa). Additionally, a questionnaire was utilized to evaluate user satisfaction. RESULTS: SRs received significantly better ratings in terms of report completeness (97.7% vs. 53.5%, p < 0.001) regarding all items. In addition, pathologies were described in more detail using SRs (70% vs. 51.1%, p < 0.001). Readability was significantly higher in all SRs when compared to FTRs (100% vs. 54.4%, p < 0.001). Mean time to complete was significantly lower (79.6 vs. 205.4 s, p < 0.001) and user satisfaction was significantly higher when using SRs (8.5 vs. 4.1, p < 0.001). Also, inter-rater reliability was very high (Fleiss' kappa 0.93). CONCLUSIONS: SRs of head and neck ultrasound examinations provide more detailed information with a better readability in a time-saving manner within medical education. Also, medical students may benefit from SRs in their learning process due to the structured approach and standardized terminology.


Assuntos
Documentação/normas , Neoplasias de Cabeça e Pescoço/diagnóstico por imagem , Cabeça/diagnóstico por imagem , Prontuários Médicos/normas , Pescoço/diagnóstico por imagem , Ultrassonografia , Confiabilidade dos Dados , Controle de Formulários e Registros , Humanos , Comunicação Interdisciplinar , Variações Dependentes do Observador , Reprodutibilidade dos Testes , Faculdades de Medicina , Estudantes de Medicina
10.
Lung ; 194(4): 571-9, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-27325047

RESUMO

PURPOSE: Bronchiolitis obliterans (BO) is an inadequately researched disease in terms of lung function as well as inflammatory profile. The short-term variation of these parameters has not been investigated. Therefore, the objective of this study was the investigation of lung function, sputum cells and cytokine profiles in BO at two visits within of four to six weeks. METHODS: Twenty patients with BO (median age = 14.6, range 8.3-24.3) performed lung function tests, airway reversibility testing and induction of sputum within four to six weeks. The cell composition in the sputum was analysed and cytokine levels of IL-1ß, IL-6 and IL-8 were determined by cytometric bead array analysis. The short-term variation was then statistically quantified and compared to that of twenty-two healthy controls. Furthermore, we compared data on short-term variation of lung function and airway inflammation with a previous investigation in these patients 10-15 months earlier. RESULTS: Patients with BO showed minimal variation of lung function (VCmax, FVC, FEV1, FEV1/VC, MEF25 and RV/TLC) and the inflammatory cell profile. The lung function data were significantly lower for FVC, FEV1, the Tiffeneau index and MEF25 compared to the control group, whereas RV/TLC was significantly increased. Analysis of the BO sputum cells showed a consistent neutrophil inflammation. The levels of inflammatory cytokines IL-1ß, IL-6 and IL-8 had a great variability. CONCLUSIONS: The short-term variability of sputum neutrophilia and lung function is low in BO patients. This finding should be considered to identify successful treatment in the individual patient and could be used as endpoints for future BO-related studies.


Assuntos
Bronquiolite Obliterante/fisiopatologia , Citocinas/metabolismo , Escarro/citologia , Escarro/metabolismo , Adolescente , Bronquiolite Obliterante/patologia , Estudos de Casos e Controles , Criança , Volume Expiratório Forçado , Humanos , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Interleucina-8/metabolismo , Neutrófilos , Volume Residual , Capacidade Vital , Adulto Jovem
11.
Acta Otolaryngol ; 144(3): 237-242, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38781053

RESUMO

BACKGROUND: Large Language Models (LLMs) might offer a solution for the lack of trained health personnel, particularly in low- and middle-income countries. However, their strengths and weaknesses remain unclear. AIMS/OBJECTIVES: Here we benchmark different LLMs (Bard 2023.07.13, Claude 2, ChatGPT 4) against six consultants in otorhinolaryngology (ORL). MATERIAL AND METHODS: Case-based questions were extracted from literature and German state examinations. Answers from Bard 2023.07.13, Claude 2, ChatGPT 4, and six ORL consultants were rated blindly on a 6-point Likert-scale for medical adequacy, comprehensibility, coherence, and conciseness. Given answers were compared to validated answers and evaluated for hazards. A modified Turing test was performed and character counts were compared. RESULTS: LLMs answers ranked inferior to consultants in all categories. Yet, the difference between consultants and LLMs was marginal, with the clearest disparity in conciseness and the smallest in comprehensibility. Among LLMs Claude 2 was rated best in medical adequacy and conciseness. Consultants' answers matched the validated solution in 93% (228/246), ChatGPT 4 in 85% (35/41), Claude 2 in 78% (32/41), and Bard 2023.07.13 in 59% (24/41). Answers were rated as potentially hazardous in 10% (24/246) for ChatGPT 4, 14% (34/246) for Claude 2, 19% (46/264) for Bard 2023.07.13, and 6% (71/1230) for consultants. CONCLUSIONS AND SIGNIFICANCE: Despite consultants superior performance, LLMs show potential for clinical application in ORL. Future studies should assess their performance on larger scale.


Assuntos
Otolaringologia , Humanos , Alemanha , Idioma , Competência Clínica , Benchmarking
12.
Methods Mol Biol ; 2644: 403-421, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37142937

RESUMO

The chorioallantoic membrane (CAM) assay is an increasingly popular method using a hen's egg as an experimental organism. Animal models have been established in scientific research for centuries. Yet, awareness of animal welfare in society rises, and the transferability of findings obtained in rodent models to human physiology is challenged. Thus, using fertilized eggs as an alternative platform for animal experimentation might be a promising alternative. The CAM assay is utilized for toxicological analysis by determination of CAM irritation as well as analysis of organ damage and ultimately death of the embryo. Furthermore the CAM provides a micromilieu suited for the implantation of xenografts. Xenogene tissues and tumors grow on the CAM due to a lack of rejection by the immune system and a dense vascular network providing oxygen and nutrients. Multiple analytical methods including in vivo microscopy and various imaging techniques are applicable to this model. Additionally, ethical aspects, a comparatively low financial burden, and low bureaucratic hurdles legitimize the CAM assay.We here describe an in ovo model utilized for xenotransplantation of a human tumor. The model can be used to evaluate the efficacy as well as the toxicity of different therapeutic agents after intravascular injection. Additionally, we present the evaluation of vascularization and viability by intravital microscopy, ultrasonography, and immunohistochemistry.


Assuntos
Galinhas , Membrana Corioalantoide , Humanos , Animais , Feminino , Membrana Corioalantoide/patologia , Sobrevivência Celular , Neovascularização Patológica/patologia , Bioensaio
13.
Front Cell Neurosci ; 17: 1189980, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37448696

RESUMO

Introduction: Preservation of residual hearing remains a great challenge during cochlear implantation. Cochlear implant (CI) electrode array insertion induces changes in the microvasculature as well as nitric oxide (NO)-dependent vessel dysfunction which have been identified as possible mediators of residual hearing loss after cochlear implantation. Methods: A total of 24 guinea pigs were randomized to receive either a CI (n = 12) or a sham procedure (sham) by performing a cochleostomy without electrode array insertion (n = 12). The hearing threshold was determined using frequency-specific compound action potentials. To gain visual access to the stria vascularis, a microscopic window was created in the osseous cochlear lateral wall. Cochlear blood flow (CBF) and cochlear microvascular permeability (CMP) were evaluated immediately after treatment, as well as after 1 and 2 h, respectively. Finally, cochleae were resected for subsequent immunohistochemical analysis of the iNOS expression. Results: The sham control group showed no change in mean CBF after 1 h (104.2 ± 0.7%) and 2 h (100.8 ± 3.6%) compared to baseline. In contrast, cochlear implantation resulted in a significant continuous decrease in CBF after 1 h (78.8 ± 8.1%, p < 0.001) and 2 h (60.6 ± 11.3%, p < 0.001). Additionally, the CI group exhibited a significantly increased CMP (+44.9% compared to baseline, p < 0.0001) and a significant increase in median hearing threshold (20.4 vs. 2.5 dB SPL, p = 0.0009) compared to sham after 2 h. Intriguingly, the CI group showed significantly lower iNOS-expression levels in the organ of Corti (329.5 vs. 54.33 AU, p = 0.0003), stria vascularis (596.7 vs. 48.51 AU, p < 0.0001), interdental cells (564.0 vs. 109.1 AU, p = 0.0003) and limbus fibrocytes (119.4 vs. 18.69 AU, p = 0.0286). Conclusion: Mechanical and NO-dependent microvascular dysfunction seem to play a pivotal role in residual hearing loss after CI electrode array insertion. This may be facilitated by the implantation associated decrease in iNOS expression. Therefore, stabilization of cochlear microcirculation could be a therapeutic strategy to preserve residual hearing.

14.
JMIR Med Educ ; 9: e49183, 2023 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-38051578

RESUMO

BACKGROUND: Large language models (LLMs), such as ChatGPT (Open AI), are increasingly used in medicine and supplement standard search engines as information sources. This leads to more "consultations" of LLMs about personal medical symptoms. OBJECTIVE: This study aims to evaluate ChatGPT's performance in answering clinical case-based questions in otorhinolaryngology (ORL) in comparison to ORL consultants' answers. METHODS: We used 41 case-based questions from established ORL study books and past German state examinations for doctors. The questions were answered by both ORL consultants and ChatGPT 3. ORL consultants rated all responses, except their own, on medical adequacy, conciseness, coherence, and comprehensibility using a 6-point Likert scale. They also identified (in a blinded setting) if the answer was created by an ORL consultant or ChatGPT. Additionally, the character count was compared. Due to the rapidly evolving pace of technology, a comparison between responses generated by ChatGPT 3 and ChatGPT 4 was included to give an insight into the evolving potential of LLMs. RESULTS: Ratings in all categories were significantly higher for ORL consultants (P<.001). Although inferior to the scores of the ORL consultants, ChatGPT's scores were relatively higher in semantic categories (conciseness, coherence, and comprehensibility) compared to medical adequacy. ORL consultants identified ChatGPT as the source correctly in 98.4% (121/123) of cases. ChatGPT's answers had a significantly higher character count compared to ORL consultants (P<.001). Comparison between responses generated by ChatGPT 3 and ChatGPT 4 showed a slight improvement in medical accuracy as well as a better coherence of the answers provided. Contrarily, neither the conciseness (P=.06) nor the comprehensibility (P=.08) improved significantly despite the significant increase in the mean amount of characters by 52.5% (n= (1470-964)/964; P<.001). CONCLUSIONS: While ChatGPT provided longer answers to medical problems, medical adequacy and conciseness were significantly lower compared to ORL consultants' answers. LLMs have potential as augmentative tools for medical care, but their "consultation" for medical problems carries a high risk of misinformation as their high semantic quality may mask contextual deficits.

15.
Cancers (Basel) ; 14(10)2022 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-35626037

RESUMO

Cold atmospheric plasma (CAP) has demonstrated promising anti-cancer effects in numerous in vitro and in vivo studies. Despite their relevance for the treatment of solid tumors, effects of CAP on tumor vasculature and microcirculation have only rarely been investigated. Here, we report the reduction of vessel density and an increase in vascular permeability and tumor cell apoptosis after CAP application. Solid tumors in the chorioallantoic membrane of chicken embryos were treated with CAP and evaluated with respect to effects of CAP on embryo survival, tumor size, and tumor morphology. Furthermore, intratumoral blood vessel density, apoptotic cell death and the tumor-associated microcirculation were investigated and compared to sham treatment. Treatment with CAP significantly reduced intratumoral vessel density while increasing the rate of intratumoral apoptosis in solid tumors. Furthermore, CAP treatment increased vascular permeability and attenuated the microcirculation by causing vessel occlusions in the tumor-associated vasculature. These effects point out the potential of CAP as a promising and yet underrated therapeutic modality for addressing the tumor vasculature in the treatment of solid tumors.

16.
Cancers (Basel) ; 13(12)2021 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-34203835

RESUMO

Despite recent advancements in tumor therapy, metastasis and tumor relapse remain major complications hindering the complete recovery of many cancer patients. Dormant tumor cells, which reside in the body, possess the ability to re-enter the cell cycle after therapy. This phenomenon has been attributed to therapy-induced senescence. We show that these cells could be targeted by the use of zinc oxide nanoparticles (ZnO NPs). In the present study, the properties of tumor cells after survival of 16 Gy gamma-irradiation were investigated in detail. Analysis of morphological features, proliferation, cell cycle distribution, and protein expression revealed classical hallmarks of senescent cells among the remnant cell mass after irradiation. The observed radiation-induced senescence was associated with the increased ability to withstand further irradiation. Additionally, tumor cells were able to re-enter the cell cycle and proliferate again after weeks. Treatment with ZnO NPs was evaluated as a therapeutical approach to target senescent cells. ZnO NPs were suitable to induce cell death in senescent, irradiation-resistant tumor cells. Our findings underline the pathophysiological relevance of remnant tumor cells that survived first-line radiotherapy. Additionally, we highlight the therapeutic potential of ZnO NPs for targeting senescent tumor cells.

17.
Nanotoxicology ; 15(5): 690-705, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33979554

RESUMO

Toxicity tests in rodents are still considered a controversial topic concerning their ethical justifiability. The chick embryo chorioallantoic membrane (CAM) assay may offer a simple and inexpensive alternative. The CAM assay is easy to perform and has low bureaucratic hurdles. At the same time, the CAM assay allows the application of a broad variety of analytical methods in the field of nanotoxicological research. We evaluated the CAM assay as a methodology for the determination of nanotoxicity. Therefore we calculated the median lethal dose (LD50), performed in vivo microscopy and immunohistochemistry to identify organ-specific accumulation profiles, potential organ damage, and the kinetics of the in vivo circulation of the nanoparticles. Zinc oxide nanoparticles were intravascularly injected on day 10 of the egg development and showed an LD50 of 17.5 µM (1.4 µg/mLeggcontent). In comparison, the LD50 of equivalent amounts of Zn2+ was 4.6 µM (0.6 µg/mLeggcontent). Silica encapsulated ZnO@SiO2 nanoparticles conjugated with fluorescein circulated in the bloodstream for at least 24 h. Particles accumulated mostly in the liver and kidney. In immunohistochemical staining, organ damage was detected only in liver tissue after intravascular injection of zinc oxide nanoparticles in very high concentrations. Zinc oxide nanoparticles showed a different pharmacokinetic profile compared to Zn2+ ions. In conclusion, the CAM assay has proven to be a promising methodology for evaluating nanotoxicity and for the assessment of the in vivo accumulation profiles of nanoparticles. These findings may qualify the methodology for risk assessment of innovative nanotherapeutics in the future.


Assuntos
Nanopartículas , Óxido de Zinco , Animais , Bioensaio , Embrião de Galinha , Membrana Corioalantoide , Nanopartículas/toxicidade , Dióxido de Silício
18.
Pediatr Pulmonol ; 56(9): 2966-2972, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34156164

RESUMO

RATIONALE: Postinfectious bronchiolitis obliterans (PIBO) is a rare, chronic respiratory condition, which follows an acute insult due to a severe infection of the lower airways. OBJECTIVES: The objective of this study was to investigate the long-term course of bronchial inflammation and pulmonary function testing in children with PIBO. METHODS: Medical charts of 21 children with PIBO were analyzed retrospectively at the Children's University Hospital Frankfurt/Main Germany. Pulmonary function tests (PFTs) with an interval of at least 1 month were studied between 2002 and 2019. A total of 382 PFTs were analyzed retrospectively and per year, the two best PFTs, in total 217, were evaluated. Additionally, 56 sputum analysis were assessed and the sputum neutrophils were evaluated. RESULTS: The evaluation of the 217 PFTs showed a decrease in FEV1 with a loss of 1.07% and a loss in z score of -0.075 per year. FEV1/FVC decreased by 1.44 per year. FVC remained stable, showing a nonsignificant increase by 0.006 in z score per year. However, FEV1 and FVC in L increased significantly with FEV1 0.032 L per cm and FVC 0.048 L/cm in height. Sputum neutrophils showed a significant increase of 2.12% per year. CONCLUSION: Our results demonstrated that in patients with PIBO pulmonary function decreased significantly showing persistent obstruction over an average follow-up period of 8 years. However, persistent lung growth was revealed. In addition, pulmonary inflammation persisted clearly showing an increasing amount of neutrophils in induced sputum. Patients did not present with a general susceptibility to respiratory infections.


Assuntos
Bronquiolite Obliterante , Bronquiolite Obliterante/diagnóstico , Bronquiolite Obliterante/etiologia , Criança , Humanos , Inflamação , Pulmão , Testes de Função Respiratória , Estudos Retrospectivos
19.
Biomedicines ; 9(10)2021 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-34680602

RESUMO

BACKGROUND: Porous polyethylene (PPE) implants are used for the reconstruction of tissue defects but have a risk of rejection in case of insufficient ingrowth into the host tissue. Various growth factors can promote implant ingrowth, yet a long-term gradient is a prerequisite for the mediation of these effects. As modification of the implant surface with nanocarriers may facilitate a long-term gradient by sustained factor release, implants modified with crosslinked albumin nanocarriers were evaluated in vivo. METHODS: Nanocarriers from murine serum albumin (MSA) were prepared by an inverse miniemulsion technique encapsulating either a low- or high-molar mass fluorescent cargo. PPE implants were subsequently coated with these nanocarriers. In control cohorts, the implant was coated with the homologue non-encapsulated cargo substance by dip coating. Implants were consequently analyzed in vivo using repetitive fluorescence microscopy utilizing the dorsal skinfold chamber in mice for ten days post implantation. RESULTS: Implant-modification with MSA nanocarriers significantly prolonged the presence of the encapsulated small molecules while macromolecules were detectable during the investigated timeframe regardless of the form of application. CONCLUSIONS: Surface modification of PPE implants with MSA nanocarriers results in the alternation of release kinetics especially when small molecular substances are used and therefore allows a prolonged factor release for the promotion of implant integration.

20.
Tissue Eng Regen Med ; 18(2): 297-303, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33515166

RESUMO

BACKGROUND: To improve the biocompatibility of porous polyethylene (PPE) implants and expand their application range for reconstructive surgery in poorly vascularized environments, implants were coated with tumor necrosis factor α (TNFα) inhibitor Etanercept. While approved for systemic application, local application of the drug is a novel experimental approach. Microvascular and mechanical integration as well as parameters of inflammation were analyzed in vivo. METHODS: PPE implants were coated with Etanercept and extracellular matrix (ECM) components prior to implantation into dorsal skinfold chambers of C57BL/6 mice. Fluorescence microscopy analyses of angiogenesis and local inflammatory response were thrice performed in vivo over a period of 14 days to assess tissue integration and biocompatibility. Uncoated implants and ECM-coated implants served as controls. RESULTS: TNFα inhibition with Etanercept led to a reduced local inflammatory response: leukocyte-endothelial cell adherence was significantly lowered compared to both control groups (n = 6/group) on days 3 and 14, where the lowest values were reached: 3573.88 leukocytes/mm-2 ± 880.16 (uncoated implants) vs. 3939.09 mm-2 ± 623.34 (Matrigel only) vs. 637.98 mm-2 + 176.85 (Matrigel and Etanercept). Implant-coating with Matrigel alone and Matrigel and Etanercept led to significantly higher vessel densities 7 and 14 days vs. 3 days after implantation and compared to uncoated implants. Mechanical implant integration as measured by dynamic breaking strength did not differ after 14 days. CONCLUSION: Our data show a reduced local inflammatory response to PPE implants after immunomodulatory coating with Etanercept in vivo, suggesting improved biocompatibility. Application of this tissue engineering approach is therefore warranted in models of a compromised host environment.


Assuntos
Polietileno , Fator de Necrose Tumoral alfa , Animais , Materiais Biocompatíveis , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Porosidade , Próteses e Implantes
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