Assessing unknown potential-quality and limitations of different large language models in the field of otorhinolaryngology.

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.

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.

ChatGPT Versus Consultants: Blinded Evaluation on Answering Otorhinolaryngology Case-Based Questions.

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.

Drug-Induced Sleep Endoscopy Findings and Hypoglossal Nerve Stimulation Therapy Outcomes.

Hypoglossal-nerve stimulation (HGNS) is an established second-line therapy for patients with obstructive sleep apnea (OSA). Existing studies investigating the effect of preoperative drug-induced sleep endoscopic (DISE) findings on HGNS outcomes have mainly focused on the apnea/hypopnea index (AHI) among polysomnography (PSG) parameters, and have less frequently tested other PSG parameters such as the apnea index (AI), hypopnea index (HI), oxygen desaturation index (ODI), snoring index, and arousal index, or patient-reported excessive daytime sleepiness. The aim of this study was to investigate the correlation between DISE findings and the above-mentioned metrics after HGNS therapy. We only included patients with DISE findings providing detailed information about the degree of the anteroposterior velar (APV), oropharyngeal lateral wall (OPLW), or tongue-base (BT) obstruction based on the velum, oropharynx, base of tongue, and epiglottis (VOTE) classification. The data of 25 patients (9 female (36%)) were retrospectively evaluated. The mean age at the date of implantation was 54.52 ± 9.61 years, and the mean BMI was 29.99 ± 3.97 kg/m2. Spearman's rho correlation coefficients were calculated. Significant correlations were found between the degree of APV obstruction and postoperative HI (r = -0.5, p < 0.05), and between the degree of OPLW obstruction and postoperative snoring index (r = 0.42, p < 0.05). BT obstruction was strongly correlated with postoperative metrics such as AHI (r = -0.57, p < 0.01), AI (r = -0.5, p < 0.05), ODI (r = -0.57, p < 0.01), ∆ AHI (r = 0.58, p < 0.01), ∆ AI (r = 0.54, p < 0.01) and ∆ ODI (r = 0.54, p < 0.01). No significant correlation was found between DISE findings and postoperative Epworth Sleepiness Scale values. These findings suggest that preoperative DISE findings, especially the degree of BT obstruction, are important for predicting an HGNS therapy outcome.

Serum Ferritin Levels in Severe Obstructive Sleep Apnea.

Obstructive sleep apnea (OSA) has been associated with various acute and chronic inflammatory diseases, as has serum ferritin, an intracellular iron storage protein. Little is known about the relationship between severity of OSA and serum ferritin levels in otherwise healthy subjects. In this study, all polysomnographic recordings, serum levels of ferritin, C-reactive protein (CRP), and hemoglobin, as well as patient files from 90 consecutive, otherwise healthy individuals with suspected OSA who presented to a tertiary sleep medical center were retrospectively analyzed. For comparison, three groups were formed based on apnea-hypopnea index (AHI; none or mild OSA: <15/h vs. moderate OSA: 15-30/h vs. severe OSA: >30/h). Serum ferritin levels were significantly positively correlated with AHI (r = 0.3240, p = 0.0020). A clear trend of higher serum ferritin levels was found when patients with severe OSA were compared to those without or with mild OSA. Serum CRP and serum hemoglobin levels did not differ significantly among OSA severity groups. Age and body-mass index (BMI) tended to be higher with increasing OSA severity. The BMI was significant higher in patients with severe OSA compared to those without or with mild (p < 0.001). Therefore, serum ferritin levels may provide a biochemical surrogate marker for OSA severity.

Central Apneic Event Prevalence in REM and NREM Sleep in OSA Patients: A Retrospective, Exploratory Study.

Patients with sleep-disordered breathing show a combination of different respiratory events (central, obstructive, mixed), with one type being predominant. We observed a reduced prevalence of central apneic events (CAEs) during REM sleep compared to NREM sleep in patients with predominant obstructive sleep apnea (OSA). The aim of this retrospective, exploratory study was to describe this finding and to suggest pathophysiological explanations. The polysomnography (PSG) data of 141 OSA patients were assessed for the prevalence of CAEs during REM and NREM sleep. On the basis of the apnea-hypopnea index (AHI), patients were divided into three OSA severity groups (mild: AHI < 15/h; moderate: AHI = 15-30/h; severe: AHI > 30/h). We compared the frequency of CAEs adjusted for the relative length of REM and NREM sleep time, and a significantly increased frequency of CAEs in NREM was found only in severely affected OSA patients. Given that the emergence of CAEs is strongly associated with the chemosensitivity of the brainstem nuclei regulating breathing mechanics in humans, a sleep-stage-dependent chemosensitivity is proposed. REM-sleep-associated neuronal circuits in humans may act protectively against the emergence of CAEs, possibly by reducing chemosensitivity. On the contrary, a significant increase in the chemosensitivity of the brainstem nuclei during NREM sleep is suggested.

Insomnia in Patients Undergoing Hypoglossal Nerve Stimulation Therapy for Obstructive Sleep Apnea.

Hypoglossal nerve stimulation (HGNS) is a treatment for obstructive sleep apnea (OSA) patients with intolerance of positive airway pressure therapy. Comorbid insomnia is quite prevalent in OSA patients. We investigated the impact of insomnia and excessive daytime sleepiness (EDS) on polysomnography metrics after HGNS treatment. Data of 27 consecutive patients (9 female; mean age 55.52 ± 8.6 years) were retrospectively evaluated. Insomnia was assessed using the ISI (insomnia severity index) and EDS using the Epworth sleepiness scale (ESS). The median ISI was reduced significantly 3 months after HGNS activation (preoperative: 19; postoperative: 14; p < 0.01). Significant correlations emerged between preoperative ISI and postoperative AHI (apnea/hypopnea index; Spearman's rho = 0.4, p < 0.05), ∆ AHI (r = −0.51, p < 0.01) and ∆ ODI (oxygen desaturation index; r = −0.48, p < 0.05). ISI correlated strongly with EES both preoperatively (r = 0.46; p < 0.02) and postoperatively (r = 0.79; p < 0.001). Therefore, HGNS therapy is associated with a significant reduction of insomnia-related symptoms, in addition to the improvement in respiratory metrics in OSA. Nonetheless, the preoperative severity of patient-reported insomnia symptoms was inversely correlated with the respiratory PSG-outcomes after HGNS. Insomnia should be considered in studies of EDS in OSA patients, especially those treated with HGNS.

Sinonasal Outcome After Endoscopic Transnasal Surgery-A Prospective Rhinological Study.

BACKGROUND: The sinonasal outcome after transnasal skull base surgery has often been neglected aside from major outcome criteria as extent of tumor resection, ophthalmological, and endocrinological parameters. OBJECTIVE: To analyze rhinological outcome after endoscopic transnasal neurosurgery. METHODS: Patients were treated using a middle turbinate-preserving transnasal endoscopic approach for sellar/parasellar lesions. As major variables, olfactory function and nose breathing ability were assessed. The study participants were investigated by odor testing ("Sniffin' sticks"), rhinomanometry, and endoscopic inspection of the nasal cavity before and 6 months after surgery. Furthermore, sinonasal-associated quality of life was measured before, immediately and 6 months after surgery with a standardized questionnaire (SNOT-20-GAV). RESULTS: Eighty-two patients (47 male, 35 female, median age 55 years) matched the inclusion criteria. Before surgery, the average odor was found to be 30.75 (≥31 = normosmia); in the postinterventional examination at 6 months, the average increased to 33.08 (n.s.). Rhinomanometric examination of binostril nasal airflow showed an average of 590.42 mL/s on inspiration before and an increase to 729.78 mL/s at 6 months after surgery. SNOT-20 symptom scores had a maximum score right after and no difference at 6 months after surgery (scores 23.76 and 14.91 vs 15.53 before surgery). CONCLUSION: Based on the study, the endoscopic transnasal technique preserving the middle turbinate has no significant negative effects on the rhinological outcome.

Short-Term Outcome of Unilateral Inspiration-Coupled Hypoglossal Nerve Stimulation in Patients with Obstructive Sleep Apnea.

Hypoglossal nerve stimulation (HGNS) is a therapeutic option for patients with obstructive sleep apnea (OSA) and intolerance of positive airway pressure (PAP) therapy. Most reported data are based on multicentre pivotal trials with selected baseline core clinical features. Our aim was to investigate polysomnography (PSG)-based outcomes of HGNS-therapy in a patient cohort with higher average AHI and BMI than previously reported. Data of 29 consecutive patients (nine female; mean age: 55.52 ± 8.6 years, mean BMI 30.13 ± 3.93 kg/m2) were retrospectively evaluated. Numerical values of PSG- based metrics were compared before and after intervention using Wilcoxon's rank-sum test. AHI (38.57/h ± 12.71, 24.43/h ± 13.3, p < 0.001), hypopnea index (24.05/h ± 9.4, 15.27/h ± 8.23, p < 0.001), apnea index (14.5/h ± 12.05, 9.17/h ± 10.86, p < 0.01), snoring index (262.68/h ± 170.35, 143.48/h ± 162.79, p < 0.001), cortical arousal index (20.8/h ± 10.34 vs. 14.9/h ± 8.36, p < 0.01) and cumulative duration of apnea and hypopnea during sleep (79.79 min ± 40.32 vs. 48.62 min ± 30.56, p < 0.001) were significantly lower after HGNS. HGNS provides an effective therapy option for selected patients not tolerating PAP-therapy with higher average AHI and BMI than usually reported. HGNS-therapy appears to suppress central nervous system arousal circuits while not eliciting peripheral autonomous sympathetic activation. Such metrics as the snoring index and the cumulative duration of respiratory events during sleep may be considered in future HGNS studies.

Cellular Immune Dysfunction in Obstructive Sleep Apnea.

Obstructive sleep apnea (OSA) is the most common sleep-related breathing disorder. Repetitive pauses in breathing during sleep cause a brief but recurrent decrease in oxygen saturation in organs and tissues (chronic intermittent tissue hypoxia). Many studies have proven a pro-inflammatory status in OSA patients. However, few reports are available on the effects of OSA on the cellular immune system, mostly focusing on single immune cell types and their subtypes. The aim of this Mini-Review is to summarize these reports, as OSA is associated with a high prevalence and comorbidities such as atherosclerosis, which are known to involve the cellular immune system.

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.

Reduced Cross-Frequency Coupling and Daytime Sleepiness in Obstructive Sleep Apnea Patients.

Obstructive sleep apnea (OSA) is associated with sleep-stage- and respiratory-event-specific sensorimotor cortico-muscular disconnection. The modulation of phase−amplitude cross-frequency coupling (PACFC) may influence information processing throughout the brain. We investigated whether sleep-stage-specific PACFC is impaired at the sensorimotor areas in OSA patients. C3 and C4 electrode EEG polysomnography recordings of 170 participants were evaluated. Different frequency band combinations were used to compute CFC modulation index (MI) to assess if MI differs between OSA and non-significant OSA patients in distinct sleep stages. We tested if the CFC-MI could predict daytime sleepiness in OSA. Theta−gamma CFC-MI at cortical sensorimotor areas was significantly reduced during all sleep stages; the delta−alpha CFC-MI was significantly reduced during REM and N1 while increasing during N2 in patients with respiratory disturbance index (RDI) > 15/h compared to those with RDI ≤ 15/h. A sleep stage classification using MI values was achieved in both patient groups. Theta−gamma MI during N2 and N3 could predict RDI and Epworth Sleepiness Scale, while delta−alpha MI during REM predicted RDI. This increase in disconnection at the cortical sensorimotor areas with increasing respiratory distress during sleep supports a cortical motor dysfunction in OSA patients. The MI provides an objective marker to quantify subjective sleepiness and respiratory distress in OSA.

Xenon-Enhanced Dynamic Dual-Energy CT Is Able to Quantify Sinus Ventilation Using Laminar and Pulsating Air-/Gas Flow Before and After Surgery: A Pilot Study in a Cadaver Model.

Background: Chronic rhinosinusitis is a common disease with a significant impact on the quality of life. Topical drug delivery to the paranasal sinuses is not efficient to prevent sinus surgery or expensive biologic treatment in a lot of cases as the affected mucosa is not reached. More efficient approaches for topical drug delivery are, therefore, necessary. In the current study, dual-energy CT (DECT) imaging was used to examine sinus ventilation before and after sinus surgery using a pulsating xenon gas ventilator in a cadaver head. Methods: Xenon gas was administered to the nasal cavity of a cadaver head with a laminar flow of 7 L/min and with pulsating xenon-flow (45 Hz frequency, 25 mbar amplitude). Nasal cavity and paranasal sinuses were imaged by DECT. This procedure was repeated after functional endoscopic sinus surgery (FESS). Based on the enhancement levels in the different sinuses, regional xenon concentrations were calculated. Results: Xenon-related enhancement could not be detected in most of the sinuses during laminar gas flow. By superimposing laminar flow with pulsation, DECT imaging revealed a xenon wash-in and wash-out in the sinuses. After FESS, xenon enhancement was immediately seen in all sinuses and reached higher concentrations than before surgery. Conclusion: Xenon-enhanced DECT can be used to visualize and quantify sinus ventilation. Pulsating air-/gas flow was superior to laminar flow for the administration of xenon to the paranasal sinuses. FESS leads to successful ventilation of all paranasal sinuses.

Obstructive Sleep Apnea in Patients with Head and Neck Cancer-More than Just a Comorbidity?

Obstructive sleep apnea is the most common type of sleep-disordered breathing with growing prevalence. Its presence has been associated with poor quality of life and serious comorbidities. There is increasing evidence for coexisting obstructive sleep apnea in patients suffering from head and neck cancer, a condition that ranks among the top ten most common types of cancer worldwide. Routinely, patients with head and neck cancer are treated with surgery, radiation therapy, chemotherapy, immunotherapy or a combination of these, all possibly interfering with the anatomy of the oral cavity, pharynx or larynx. Thus, cancer treatment might worsen already existing obstructive sleep apnea or trigger its occurrence. Hypoxia, the hallmark feature of obstructive sleep apnea, has an impact on cancer biology and its cure. Early diagnosis and sufficient treatment of coexisting obstructive sleep apnea in patients with head and neck cancer may improve quality of life and could also potentially improve oncological outcomes.

Intensity of Respiratory Cortical Arousals Is a Distinct Pathophysiologic Feature and Is Associated with Disease Severity in Obstructive Sleep Apnea Patients.

BACKGROUND: We investigated whether the number, duration and intensity of respiratory arousals (RA) on C3-electroencephalographic (EEG) recordings correlate with polysomnography (PSG)-related disease severity in obstructive sleep apnea (OSA) patients. We also investigated if every patient might have an individual RA microstructure pattern, independent from OSA-severity. METHODS: PSG recordings of 20 OSA patients (9 female; age 27-80 years) were analyzed retrospectively. Correlation coefficients were calculated between RA microstructure (duration, EEG-intensity) and RA number and respiratory disturbance index (RDI), oxygen desaturation index (ODI) and arousal index (AI). Intraclass correlations (ICC) for both RA duration and intensity were calculated. Sleep stage-specific and apnea- and hypopnea-specific analyses were also done. The probability distributions of duration and intensity were plotted, interpolated with a kernel which fits the distribution. A Bayesian posterior distribution analysis and pair-wise comparisons of each patient with all other 19 patients were performed. RESULTS: Of the analyzed 2600 RA, strong positive correlations were found between average RA intensity and both RDI and AI. The number of PSG-recorded RA was strongly positively correlated with RDI. Significant correlations between average RA intensity in REM, NREM2 and NREM3 sleep stages and total ODI were identified. No sleep stage-specific correlations of arousal microstructure with age, sex, RDI or AI were identified. Although between-subjects ICC values were <0.25, within-subject ICC values were all >0.7 (all p < 0.05). While apnea-related RA duration did not differ from hypopnea-related RA duration, RA intensity was significantly higher (p = 0.00135) in hypopneas than in apneas. A clear individual pattern of arousal duration for each patient was made distinct. For arousal intensity, a Gaussian distribution was identified in most patients. The Bayesian statistics regarding the arousal microstructure showed significant differences between each pair of patients. CONCLUSIONS: Each individual patient with OSA might have an individual pattern of RA intensity and duration indicating a distinct individual pathophysiological feature. Arousal intensity was significantly higher in hypopneic than in apneic events and may be related causally to the diminished (compared to apneas) respiratory distress associated with hypopneas. RA intensity in REM, NREM2 and NREM3 strongly correlated with ODI.

OSA in patients with head and neck cancer is associated with cancer size and oncologic outcome.

PURPOSE: Obstructive sleep apnea (OSA) is associated with severe daytime sleepiness and reduced quality of life. These symptoms are also present in patients with squamous cell carcinoma of the head and neck (SCCHN) before, during and after treatment, so that comorbidity cannot be excluded. The aim was to evaluate the prevalence of OSA and its impact on the quality of life in patients with oropharyngeal, hypopharyngeal and lateral tongue SCCHN in a prospective study. METHODS: We performed cardiorespiratory home sleep apnea testing and recorded sleep-related patient-reported outcomes in 33 patients with confirmed oropharyngeal, hypopharyngeal and lateral tongue SCCHN. We correlated the sleep-related variables to oncologic variables and endpoints. RESULTS: Five female and 28 male patients with SCCHN (aged 46-77 years) were recruited. Thirty patients (90%) had OSA as defined by an Apnea/Hypopnea Index (AHI) > 5 /h before treatment. Evaluation after treatment, which was possible in 17 patients, showed OSA in 16 patients (94%). Radiologic primary tumor size showed significant positive correlation with AHI and apnea-index. Tumor recurrence and tumor-related mortality showed significant positive association with AHI. PSQI of these patients showed at least a moderate sleep disturbance. EORTC QLQ c30 questionnaire showed reduced values for all tested qualities, in particular for fatigue, insomnia, pain and financial distress. CONCLUSION: Obstructive sleep apnea is a significant comorbidity in patients with SCCHN. Pre-interventional AHI may be correlated with the oncologic outcome. Further research is needed to further describe the course of OSA and its treatment before, during and after therapy.