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Objective: To explore Chat Generative Pretrained Transformer's (ChatGPT's) capability to create multiple-choice questions about otorhinolaryngology (ORL)., Study Design: Experimental question generation and exam simulation., Setting: Tertiary academic center., Methods: ChatGPT 3.5 was prompted: "Can you please create a challenging 20-question multiple-choice questionnaire about clinical cases in otolaryngology, offering five answer options?." The generated questionnaire was sent to medical students, residents, and consultants. Questions were investigated regarding quality criteria. Answers were anonymized and the resulting data was analyzed in terms of difficulty and internal consistency., Results: ChatGPT 3.5 generated 20 exam questions of which 1 question was considered off-topic, 3 questions had a false answer, and 3 questions had multiple correct answers. Subspecialty theme repartition was as follows: 5 questions were on otology, 5 about rhinology, and 10 questions addressed head and neck. The qualities of focus and relevance were good while the vignette and distractor qualities were low. The level of difficulty was suitable for undergraduate medical students (n = 24), but too easy for residents (n = 30) or consultants (n = 10) in ORL. Cronbach's α was highest (.69) with 15 selected questions using students' results., Conclusion: ChatGPT 3.5 is able to generate grammatically correct simple ORL multiple choice questions for a medical student level. However, the overall quality of the questions was average, needing thorough review and revision by a medical expert to ensure suitability in future exams., Competing Interests: The authors declare that there is no conflict of interest., (© 2024 The Author(s). OTO Open published by Wiley Periodicals LLC on behalf of American Academy of Otolaryngology–Head and Neck Surgery Foundation.)

Objectives: The aim of this study is to compare voice outcomes in open partial horizontal laryngectomy vs. total laryngectomy (TL) with voice prosthesis., Methods: In this retrospective monocentric study patients undergoing OPHL or TL with voice prosthesis were enrolled during the usual oncological follow-up consultations at the Otolaryngology and Audiology Unit of a University Hospital in the period between July 2022 and June 2023. Acoustic analysis (F0, HNR, NHR), maximum phonation time, I-SECEL and INFV0 scale were used to assess voice outcome., Results: Forty-three patients were enrolled. Voices of patients undergoing LT were better in quality of voice (V0) at INFV0 scale. The scores in I-SECEL and acoustic analysis were comparable., Conclusions: Voice quality could be slight better in patients undergoing TL with voice prosthesis than those undergoing OPHL., (© 2024. The Author(s).)

Purpose: To compare the audiological outcomes, tympanic membrane (TM) healing rates and complication rates in patients undergoing endoscopic underlay and over-under tympanoplasty type I (TTI)., Methods: The study includes 95 patients who underwent endoscopic TTI in the period between 2018 and 2023: 56% of the patients had the underlay technique and 41% had the over-under technique. Data regarding pre- and postoperative hearing, perforation characteristics, surgical procedures, graft types and complications were retrospectively analyzed. Audiometrical assessment included air conduction (AC) and bone conduction (BC) pure tone averages (PTA) and air-bone gap (ABG), pre- and postoperatively., Results: Both underlay and over-under techniques significant improved AC PTA, with a mean ABG improvements of 5.9 dB and 7.2 dB, respectively. There was no significant difference in BC PTA between pre- and post-operative, indicating no inner ear damage in both techniques. The over-under technique showed a significantly higher TM closure rate (94.4%) compared to the underlay technique (80.6%). Complications were rare, with only one case of TM lateralization requiring revision surgery., Conclusions: Endoscopic TTI is an effective treatment in improving auditory function in chronic middle ear diseases. In our cohort, the detachment of the umbo does not negatively influence the postoperative hearing results and does not increase rate of complications. Moreover, the over-under technique demonstrates superior TM closure rates, making it a valuable option for specific cases. However, future prospective studies with larger sample sizes and longer term follow-up are needed to validate these findings and provide more comprehensive insights., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: Squamous cell carcinoma of the nasal vestibule (NV SCC) is a head and neck malignancy for which there is no established consensus on most aspects of clinical management. The purpose of this document is to give updated recommendations that incorporate recent evidence on its clinical characteristics and the high efficacy of brachytherapy as primary treatment modality., Methods: A working group consisting of the members of the Scientific Committee for Oncology and Reconstructive Surgery of the Italian Society of Otorhinolaryngology Head and Neck Surgery and radiation oncologists expert in brachytherapy was formed to achieve a consensus., Results: Consensus was reached on a set of recommendations, proposing a refined anatomical definition of the nasal vestibule, a novel T staging system of the NV SCC, and brachytherapy as standard of care, with a new method for catheter implantation., Conclusions: The Committee emphasises the critical role of an accurate classification in clinical practice and encourages further research to validate the novel staging system and further improve treatment strategies. Where appropriate, it is recommended that patients be referred to centres with specific experience in brachytherapy for NV SCC., (Copyright © 2024 Società Italiana di Otorinolaringoiatria e Chirurgia Cervico-Facciale, Rome, Italy.)

Purpose: To compare hearing results and complication rates between two groups of patients operated on by endoscopic stapes surgery (ESS) for otosclerosis, either with CO 2 fiber laser or microdrill., Methods: A case-control study was performed. All consecutive cases of CO 2 fiber laser ESS operated at a single center during the period 2017-2020 (case group) were matched to a control group of patients operated by traditional technique, according to year of surgery, preoperative mean air-bone gap, sex and age. Audiological data from preoperative and postoperative examinations and complication rates were compared., Results: 46 cases were included. Mean operative time was significantly longer in the laser cohort (65 min) than in the drill one (45 min) (p = 0.003). Similar results were found in the two groups regarding the mean postoperative BC-PTA. The high-frequency bone conduction resulted significantly higher in the laser group (p = 0.002), suggesting an overclosure effect in the laser group. Consistently, a significant improvement of the BC-PTA threshold at 2000 Hz postoperatively was found in the laser group (p = 0.034). The postoperative AC-PTA significantly improved in both groups at all frequencies (p < 0.05), except for the AC threshold at 8 kHz. Similar rates of complications were found in the two groups., Conclusion: This study is the first to compare hearing results and complications between CO 2 fiber laser and microdrill in ESS. Our results demonstrated similar functional outcomes between the two groups, confirming ESS as safe and effective, regardless of the technique used., (© 2022. The Author(s).)

Horizontal glottectomy (HG) is a particular type of partial laryngectomy indicated for exclusive glottic tumor with anterior commissure involvement. The purpose of this study is to systematically review the literature about functional and oncological outcome of HG. This systematic review adhered to the recommendations of the PRISMA (Preferred Reporting Items of Systematic Reviews and Meta-analysis) 2009 guidelines. Articles mentioning patients undergoing HG for laryngeal squamous cell carcinoma were included. A total of 14 articles were selected and reviewed from 19 identified. The whole study population consisted of 420 patients who underwent HG. Three hundred and thirty-nine patients out of 359 were staged as T1. The range of post-operative follow-up was 5 months to 10 years. Fifty-five recurrences were experienced, being local, regional and distant in 35, 12 and 8 patients, respectively. Laryngeal preservation rate was 93.6%. Nasogastrict tube was removed on average after 10.1 days. The tracheostomy was maintained for 11.3 days. Mean hospitalization lasted for 11.7 days. According to the results of this systematic review, HG is an oncologically safe surgical option for T1a-T1b glottic tumors with oncological outcomes comparable to other treatment. HG could be a good therapeutical choice whenever poor laryngeal exposure and/or patient's refusal of radiotherapy are encountered, or when patient's medical history represents a contraindication for radiation therapy., Competing Interests: The authors declare no conflict of interest.

Background: Pancreatic neuroendocrine tumors (PNETs) are rare, and metastases when present are most commonly found in the liver or the peripancreatic lymph nodes. In this study, we present a patient who developed a metastatic PNET in the liver in the setting of multiple concomitant autoimmune disorders, including pernicious anemia and atrophic gastritis with hypergastrinemia. Case presentation: The patient is a 70-year-old woman with a history of Hashimoto's thyroiditis, thymoma, gastric carcinoid tumors, and autoimmune atrophic gastritis with pernicious anemia. She was found to have a 2 cm mass in the pancreaticoduodenal groove originating from the pancreas. A preoperative endoscopic ultrasound with fine-needle aspiration showed a well-differentiated PNET. During surgery, she was found to have multiple subcentimeter liver lesions, which on frozen section were shown to be a metastatic neuroendocrine tumor. After surgical resection, final pathology revealed a PNET with metastases to the liver. The metastatic lesions stained positive for gastrin. Conclusion: We were only able to find one other example in the literature of a PNET occurring in association with pernicious anemia. Our patient developed a metastatic PNET in the setting of multiple autoimmune disorders, including pernicious anemia., Competing Interests: No competing financial interests exist.

The activation of the GABAergic system has been shown to protect brain tissues against the damage that occurs after cerebral ischaemia. On the other hand, the taurine analogues (±)Piperidine-3-sulphonic- (PSA), 2-aminoethane phosphonic- (AEP), 2-(N-acetylamino) cyclohexane sulfonic-acids (ATAHS) and 2-aminobenzene sulfonate-acids (ANSA) have been reported to block GABA metabolism by inhibiting rabbit brain GABA aminotransferase and to increase GABA content in rabbit brain slices. The present investigation explored the neuroprotection provided by GABA, Vigabatrin (VIGA) and taurine analogues in the course of oxygen-glucose deprivation and reperfusion induced damage of rabbit brain slices. Tissue damage was assessed by measuring the release of glutamate and lactate dehydrogenase (LDH) during reperfusion and by determining final tissue water gain, measured as the index of cell swelling. GABA (30-300 μM) and VIGA (30-300 μM) significantly antagonised LDH and glutamate release, as well as tissue water gain caused by oxygen-glucose deprivation and reperfusion. Lower (1-10 μM) or higher concentrations (up to 3,000 μM) were ineffective. ANSA, PSA and ATAHS significantly reduced glutamate and LDH release and tissue water gain in a range of concentrations between 30 and 300 μM. Lower (0-10 μM) or higher (up to 3,000 μM) concentrations were ineffective. Both mechanisms suggest hormetic ("U-shaped") effects. These results indicate that the GABAergic system activation performed directly by GABA or indirectly through GABA aminotransferase inhibition is a promising approach for protecting the brain against ischemia and reperfusion-induced damage.

The aim of the present investigation was to assess neuroprotection exerted by diazepam (0.1-25 microM) in rat cortical brain slices subjected to oxygen-glucose deprivation and reoxygenation. Neuronal injury and neuroprotection were assessed by measuring the release of glutamate and lactate dehydrogenase and tissue water content. Results demonstrate that diazepam exerted neuroprotective effects according to a "U-shaped", hormetic-like, concentration-response curve, with an efficacy window of 0.5-5 microM concentration. Flumazenil (20 microM) fully antagonised neuroprotection afforded by 5 microM diazepam. In conclusion, the hormetic response of diazepam should be taken into consideration when designing experiments aimed at assessing diazepam neuroprotection against ischemia/reoxygenation injury.

Elevation of brain temperature after stroke can lead to severe brain injury and even a moderate hyperthermia correlates with increased nervous damage. The role of endogenous cryogens in the pathways that down-regulate body temperature are of overwhelming interest in view of their effectiveness in protecting brain from such damage. The aim of the present work was to study whether heat stress (HS) or fever generates brain homeostatic responses aimed at counteracting the resulting rise in body temperature. Conscious rabbits, with cannulas chronically implanted in the cisterna magna and lateral ventricle, underwent HS (50 min, 40 degrees C) or were injected with 25 ng of endogenous pyrogen IL-1beta, while cerebrospinal fluid (CSF) levels of amino acids involved in central mechanisms of thermoregulation like taurine, GABA, aspartate and glutamate were monitored. The concentrations of some CSF cations (Na(+), K(+), Mg(2+) and Ca(2+)) were also determined in view of their purported role (sodium and calcium in particular) in establishing the thermal set point within the hypothalamus. Results show that during HS-induced hyperthermia, CSF taurine and GABA levels were significantly increased. On the contrary, IL-1beta caused an increase in CSF taurine and, concurrently, a decrease in CSF GABA. Aspartate and glutamate did not change in both conditions. Furthermore, among CSF cations, only calcium and sodium underwent changes. In particular, calcium content increased both in HS- and febrile-animals, while CSF sodium decreased significantly only under IL-1beta-injected treatment. In conclusion, GABA and taurine contribute as endogenous cryogens in a different fashion to the central mechanisms, which regulate dissipation of body heat in hyperthermia or heat production in fever, possibly in coordination with extracellular calcium and sodium.

The use of the antiepileptic drug, 4-aminobutyrate transaminase (GABA-T) inhibitor vigabatrin (VIGA), has been recently cautioned because it is associated to irreversible field defects from damage of the retina. Since novel GABA-T inhibitors might prove useful in epilepsy or other CNS pathologies as VIGA substitutes, the aim of the present investigation was to characterize the biochemical properties of some taurine analogues (TA) previously shown to act as GABA-T inhibitors. These include (+/-)piperidine-3-sulfonic acid (PSA), 2-aminoethylphosphonic acid (AEP), (+/-)2-acetylaminocyclohexane sulfonic acid (ATAHS) and 2-aminobenzenesulfonate (ANSA). Kinetic analysis of the activity of partially purified rabbit brain GABA-T in the presence of VIGA and TA showed that PSA and AEP caused a linear, mixed-type inhibition (Ki values 364 and 1010 microM, respectively), whereas VIGA, ANSA and ATAHS behaved like competitive inhibitors (Ki values 320, 434 and 598 microM, respectively). Among the compounds studied, only VIGA exerted a time-dependent, irreversible inhibition of the enzyme, with Ki and k(inact) values of 773 microM and 0.14 min(-1), respectively. Furthermore, the ability of VIGA and TA to enhance GABA-ergic transmission was assessed in rabbit brain cortical slices by NMR quantitative analysis. The results demonstrate that VIGA as well as all TA promoted a significant increase of GABA content. In conclusion, PSA, ANSA and ATAHS, reversible GABA-T inhibitors with Ki values close to that of VIGA, represent a new class of compounds, susceptible of therapeutic exploitation in many disorders associated with low levels of GABA in brain tissues.

1. In order to ascertain whether both GABA(A) and GABA(B), or only GABA(B) receptors, directly modulate thermoregulation in conscious rabbits, GABA(A)/GABA(B) agonist and antagonist agents were injected intracerebroventricularly in conscious rabbits while monitoring changes in rectal temperature (RT), gross motor behaviour (GMB) and electrocorticogram (ECoG) power spectra (ps) from sensorimotor cortices. 2. GABA (48 micromol), nipecotic acid (50 nmol), THIP (60 nmol), muscimol (18 nmol) and baclofen (8 nmol) induced hypothermia (-deltaRTmax values of 1.70+/-0.1, 1.4+/-0.2, 1.0+/-0.4, 1.1+/-0.2 and 1.6+/-0.3 degrees C, respectively), accompanied by inhibition of GMB and ECoG synchronization. THIP increased ps at delta frequency band (1.1-3.3 Hz), while GABA, nipecotic acid, muscimol and baclofen did the same at both delta and (4.6-6.5 Hz) frequency bands. ECoG ps changes were concomitant or even preceded hypothermia. 3. Bicuculline (1.8 nmol) induced hyperthermia (deltaRTmax 1.2+/-0.5 degrees C) and slight excitation of GMB, while CGP35348 (1.2 micromol) did not affect RT nor GMB. Both compounds did not affect ECoG ps. 4. Bicuculline potentiated muscimol-induced hypothermia, inhibition of GMB and synchronization of ECoG, while CGP35348 fully antagonized these effects. 5. In conclusion, the present results, while confirming the prevailing role of GABA(B), also outline a direct involvement of GABA(A) receptors in the central mechanisms of thermoregulation. Ascending inhibition towards discrete cortical areas controlling muscular activity and thermogenesis may result from GABA receptor activation in neurones proximal to the ventricles, thus contributing to hypothermia, although hypothermia-induced reduction of neuronal activity of these cortical areas cannot be ruled out.

(1) Taurine and GABA are recognized as endogenous cryogens. In a previous study, some structural analogues of taurine, namely 6-aminomethyl-3-methyl-4H-1,2,4-benzothiadiazine 1,1-dioxide (TAG), 2-aminoethylarsonic (AEA), 2-hydroxyethanesulfonic (ISE) and (+/-)cis-2-aminocyclohexane sulfonic acids (CAHS) have been shown to displace [(3)H]taurine binding from rabbit brain synaptic membrane preparations, without interacting either with GABA-ergic systems, nor with taurine uptake mechanism, thus behaving like direct taurinergic agents. (2) To answer the question whether the role of taurine as an endogenous cryogen depends on the activation of GABA receptors or that of specific taurine receptor(s), taurine or the above structural analogues were injected intracerebroventricularly in conscious, restrained rabbits singularly or in combination and their effects on rectal (RT)- and ear-skin temperature and gross motor behavior (GMB) were monitored. (3) Taurine (1.2 x 10(-6)-4.8 x 10(-5) mol) induced a dose-related hypothermia, vasodilation at ear vascular bed and inhibition of GMB. CAHS, at the highest dose tested (4.8 x 10(-5) mol) induced a taurine-like effect either on RT or GMB. On the contrary ISE, injected at the same doses of taurine, induced a dose-related hyperthermia, vasoconstriction and excitation of GMB. AEA and TAG caused a dose-related hyperthermia, but at doses higher than 1.2 x 10(-7) mol caused death within 24 h after treatment. (4) CAHS (4.8 x 10(-5) mol) antagonized the hyperthermic effect induced by TAG (1.2 x 10(-6) mol), AEA (1.2 x 10(-8) mol) or ISE (4.8 x 10(-5) mol). (5) In conclusion, these findings may indicate the existence of a recognition site specific for taurine, responsible for its effects on thermoregulation.

1. The aim of this study was to find taurinergic compounds that do not interact with brain GABA ergic systems. 2. Washed synaptic membranes (SM) from whole rabbit brain were able to bind [(3)H]muscimol. Saturation experiments of the binding of [(3)H]GABA to GABA(B) receptors showed that SM possess two binding components; twice Triton X-100-treated SM contained 0.048 mmol endogenous taurine/kg protein and bound [(3)H]taurine in a saturable manner (K(d)=249.0+/-6.3 nM and B(max)=3.4+/-1.0 pmol mg(-1) prot). 3. Among the 19 structural analogues of taurine, 6-aminomethyl-3-methyl-4H-1,2,4-benzothiadiazine 1,1-dioxide (TAG), 2-aminoethylarsonic (AEA), 2-hydroxyethanesulfonic (ISE) and (+/-)cis-2-aminocyclohexane sulfonic acids (CAHS) displaced [(3)H]taurine binding (K(i)=0.13, 0.13, 13.5 and 4.0 micro M, respectively). These analogues did not interact with GABA(A) and GABA(B) receptors and did not affect taurine- and GABA-uptake systems and GABA-transaminase activity. 4. 3-Aminopropanesulfonic acid (OMO), beta-alanine, pyridine-3-sulfonic acid, N,N,N-trimethyltaurine (TMT), 2-(guanidino)ethanesulfonic acid (GES), ethanolamine-O-sulphate, N,N-dimethyltaurine (DMT), taurine and (+/-)piperidine-3-sulfonic acid (PSA) inhibited [(3)H]muscimol binding to GABA(A) receptors with different affinities (K(i)=0.013, 7.9, 24.6, 47.5, 52.0, 91.0, 47.5, 118.1 and 166.3 micro M, respectively). Taurine, 2-aminoethylphosphonic acid, DMT, TMT and OMO inhibited the binding of [(3)H]GABA to GABA(B) receptors with K(i)'s in the micro M range (0.8, 3.5, 4.4, 11.3 and 5.0, respectively). GES inhibited taurine uptake (IC(50)=3.72 micro M) and PSA GABA transaminase activity (IC(50)=103.0 micro M). 5. In conclusion, AEA, TAG, ISE and CAHS fulfill the criteria for taurinergic agents.