ChatGPT as an information tool in rhinology. Can we trust each other today?

PURPOSE: ChatGPT (Chat-Generative Pre-trained Transformer) has proven to be a powerful information tool on various topics, including healthcare. This system is based on information obtained on the Internet, but this information is not always reliable. Currently, few studies analyze the validity of these responses in rhinology. Our work aims to assess the quality and reliability of the information provided by AI regarding the main rhinological pathologies. METHODS: We asked to the default ChatGPT version (GPT-3.5) 65 questions about the most prevalent pathologies in rhinology. The focus was learning about the causes, risk factors, treatments, prognosis, and outcomes. We use the Discern questionnaire and a hexagonal radar schema to evaluate the quality of the information. We use Fleiss's kappa statistical analysis to determine the consistency of agreement between different observers. RESULTS: The overall evaluation of the Discern questionnaire resulted in a score of 4.05 (± 0.6). The results in the Reliability section are worse, with an average score of 3.18. (± 1.77). This score is affected by the responses to questions about the source of the information provided. The average score for the Quality section was 3.59 (± 1.18). Fleiss's Kappa shows substantial agreement, with a K of 0.69 (p < 0.001). CONCLUSION: The ChatGPT answers are accurate and reliable. It generates a simple and understandable description of the pathology for the patient's benefit. Our team considers that ChatGPT could be a useful tool to provide information under prior supervision by a health professional.

Bow and Lean Test for Rare Variants of Vertical Semicircular Canal BPPV.

OBJECTIVE: The objective of this study was to assess the clinical significance of the Bow and Lean Test (BLT) for the diagnosis of different variants of vertical canal Benign Paroxysmal Positional Vertigo (BPPV). BLT is commonly used for diagnoses of lateral semicircular canal (LSC) BPPV. However, vertical nystagmus in the BLT may indicate the presence of other variants such as PSC-BPPV. METHODS: 567 patients with vertical canal BPPV were recruited. Patients with anterior semicircular canal (ASC) or PSC-BPPV were weekly examined until the negativization of BPPV. Nystagmus characteristics during BLT were analyzed. RESULTS: Of 567 patients with vertical canal BPPV, 1.4% had ASC-BPPV. BLT was positive in 155 patients, showing patterns like down-beating nystagmus in bowing and no nystagmus in leaning (15.52% of patients), and down-beating in bowing and up-beating in leaning (6.17%), which was predominantly present in PSC-canalolithiasis. Statistically significant differences were observed in the direction of nystagmus provoked by BLT in PSC-BPPV subtypes. No significant differences were found in nystagmus latency or duration during BLT positions. Among BPPV subtypes, there was a significant difference in nystagmus duration and latency, especially between cupulolithiasis and other variants. BLT's sensitivity was 0.93 in bowing and 1 in a leaning position, while specificity was 0.93 and 0.82 respectively. CONCLUSION: Beyond the LSC, the BLT has expanded to other variants. However, study results differ likely due to variations in patient characteristics and test execution. Currently, no specific features for ASC have been found to differentiate it from PSC-BPPV limiting the test's use for this variant. LEVEL OF EVIDENCE: 3, according to Oxford Center for Evidence-Based Medicine Laryngoscope, 134:2405-2410, 2024.

Cocoa Polyphenols Prevent Age-Related Hearing Loss and Frailty in an In Vivo Model.

Age-related hearing loss (ARHL) impairs the quality of life in elderly persons. ARHL is associated with comorbidities, such as depression, falls, or frailty. Frailty syndrome is related to poor health outcomes in old age. ARHL is a potentially modifiable risk factor for frailty. Oxidative stress has been proposed as a key factor underlying the onset and/or development of ARHL and frailty. Cocoa has high levels of polyphenols and provides many health benefits due to its antioxidant properties. Male and female C57Bl/6J mice were randomly assigned to two study groups: animals receiving a cocoa-supplemented diet and the other receiving a standard diet. Then, at the ages of 6, 14, and 22 months, hearing and frailty were measured in all mice. Auditory steady-state responses (ASSR) threshold shifts were measured to different frequencies. The frailty score was based on the "Valencia Score" adapted to the experimental animals. The total antioxidant capacity and total polyphenols in urine samples were also measured. Significant improvements in hearing ability are observed in the cocoa groups at 6, 14, and 22 months compared to the no cocoa group. The cocoa diet significantly retards the development of frailty in mice. Cocoa increases the concentration of polyphenols excreted in the urine, which increases the total antioxidant capacity. In conclusion, cocoa, due to its antioxidant properties, leads to significant protection against ARHL and frailty.

Cocoa Polyphenol Extract Inhibits Cellular Senescence via Modulation of SIRT1 and SIRT3 in Auditory Cells.

Cocoa, rich in polyphenols, has been reported to provide many health benefits due to its antioxidant properties. In this study, we investigated the effect of Cocoa polyphenols extract (CPE) against oxidative stress-induced cellular senescence using a hydrogen peroxide (H2O2)-induced cellular senescence model in three auditory cells lines derived from the auditory organ of a transgenic mouse: House Ear Institute-Organ of Corti 1 (HEI-OC1), Organ of Corti-3 (OC-k3), and Stria Vascularis (SV-k1) cells. Our results showed that CPE attenuated senescent phenotypes, including senescence-associated ß-galactosidase expression, cell proliferation, alterations of morphology, oxidative DNA damage, mitochondrial dysfunction by inhibiting mitochondrial reactive oxygen species (mtROS) generation, and related molecules expressions such as forkhead box O3 (FOXO3) and p53. In addition, we determined that CPE induces expression of sirtuin 1 (SIRT1) and sirtuin 3 (SIRT3), and it has a protective role against cellular senescence by upregulation of SIRT1 and SIRT3. These data indicate that CPE protects against senescence through SIRT1, SIRT3, FOXO3, and p53 in auditory cells. In conclusion, these results suggest that Cocoa has therapeutic potential against age-related hearing loss (ARHL).

Preventive Effect of Cocoa Flavonoids via Suppression of Oxidative Stress-Induced Apoptosis in Auditory Senescent Cells.

Presbycusis or Age-related hearing loss (ARHL) is a sensorineural hearing loss that affects communication, leading to depression and social isolation. Currently, there are no effective treatments against ARHL. It is known that cocoa products have high levels of polyphenol content (mainly flavonoids), that are potent anti-inflammatory and antioxidant agents with proven benefits for health. The objective is to determine the protective effect of cocoa at the cellular and molecular levels in Presbycusis. For in vitro study, we used House Ear Institute-Organ of Corti 1 (HEI-OC1), stria vascularis (SV-k1), and organ of Corti (OC-k3) cells (derived from the auditory organ of a transgenic mouse). Each cell line was divided into a control group (CTR) and an H2O2 group (induction of senescence by an oxygen radical). Additionally, every group of every cell line was treated with the cocoa polyphenolic extract (CPE), measuring different markers of apoptosis, viability, the activity of antioxidant enzymes, and oxidative/nitrosative stress. The data show an increase of reactive oxidative and nitrogen species (ROS and RNS, respectively) in senescent cells compared to control ones. CPE treatment effectively reduced these high levels and correlated with a significant reduction in apoptosis cells by inhibiting the mitochondrial-apoptotic pathway. Furthermore, in senescence cells, the activity of antioxidant enzymes (Superoxide dismutase, SOD; Catalase, CAT; and Glutathione peroxidase, GPx) was recovered after CPE treatment. Administration of CPE also decreased oxidative DNA damage in the auditory senescent cells. In conclusion, CPE inhibits the activation of senescence-related apoptotic signaling by decreasing oxidative stress in auditory senescent cells.

Role of Oxidative Stress in the Senescence Pattern of Auditory Cells in Age-Related Hearing Loss.

Age-related hearing loss (ARHL) is an increasing and gradual sensorineural hearing dysfunction. Oxidative stress is an essential factor in developing ARHL; additionally, premature senescence of auditory cells induced by oxidative stress can produce hearing loss. Hydrogen peroxide (H2O2) represents a method commonly used to generate cellular senescence in vitro. The objective of the present paper is to study H2O2-induced senescence patterns in three auditory cell lines (House Ear Institute-Organ of Corti 1, HEI-OC1; organ of Corti, OC-k3, and stria vascularis, SV-k1 cells) to elucidate the intrinsic mechanisms responsible for ARHL. The auditory cells were exposed to H2O2 at different concentrations and times. The results obtained show different responses of the hearing cells concerning cell growth, ß-galactosidase activity, morphological changes, mitochondrial activation, levels of oxidative stress, and other markers of cell damage (Forkhead box O3a, FoxO3a, and 8-oxoguanine, 8-oxoG). Comparison between the responses of these auditory cells to H2O2 is a helpful method to evaluate the molecular mechanisms responsible for these auditory cells' senescence. Furthermore, this in vitro model could help develop anti-senescent therapeutic strategies for the treatment of AHRL.

Antitumor Activity of Nanoparticles Loaded with PHT-427, a Novel AKT/PDK1 Inhibitor, for the Treatment of Head and Neck Squamous Cell Carcinoma.

Currently, new treatments are required to supplement the current standard of care for head and neck squamous cell carcinoma (HNSCC). The phosphatidylinositol3-kinase (PI3K) signaling pathway is commonly altered and activated in HNSCC. PHT-427 is a dual PI3K-mammalian target of the AKT/PDK1 inhibitor; however, to the best of our knowledge, the effect of the PHT-427 inhibitor on HNSCC has not been investigated. This study aims to evaluate the antitumoral effect of PHT-427-loaded polymeric nanoparticles based on α-tocopheryl succinate (α-TOS). The in vitro activity of PHT-427 was tested in hypopharynx carcinoma squamous cells (FaDu) to measure the cell viability, PI3KCA/AKT/PDK1 gene expression, and PI3KCA/AKT/PDK1 levels. Apoptosis, epidermal growth factor receptor (EGFR), and reactive oxygen species (ROS) were also measured. The presence of PHT-427 significantly enhances its antiproliferative and proapoptotic activity by inactivating the PI3K/AKT/PDK1 pathway. Nanoparticles (NPs) effectively suppress AKT/PDK1 expression. Additionally, NPs loaded with PHT-427 produce high oxidative stress levels that induce apoptosis. In conclusion, these results are promising in the use of this nanoformulation as a PHT-427 delivery system for effective HNSCC treatment.

Paclitaxel-loaded polymeric nanoparticles based on α-tocopheryl succinate for the treatment of head and neck squamous cell carcinoma: in vivo murine model.

The prognosis of patients with recurrent or metastatic head and neck squamous cell cancer (HNSCC) is generally poor. New treatments are required to supplement the current standard of care. Paclitaxel (PTX), an effective chemotherapeutic for HNSCC, has serious side effects. A polymeric nanocarrier system was developed for the delivery of PTX to improve HNSCC treatment. This study aimed to evaluate the antitumor efficacy of PTX-loaded polymeric nanoparticles based on α-TOS (PTX-NPs) administered by direct intratumoral injection into a Hypopharynx carcinoma squamous cells (FaDu) tumor xenograft mouse model. The nanocarrier system based on block copolymers of polyethylene glycol (PEG) and a methacrylic derivative of α-TOS was synthesized and PTX was loaded into the delivery system. Tumor volume was measured to evaluate the antitumor effect of the PTX-NPs. The relative mechanisms of apoptosis, cell proliferation, growth, angiogenesis, and oxidative and nitrosative stress were detected by Western blotting, fluorescent probes, and immunohistochemical analysis. The antitumor activity results showed that compared to free PTX, PTX-NPs exhibited much higher antitumor efficacy and apoptosis-inducing in a FaDu mouse xenograft model and demonstrated an improved safety profile. Ki-67, EGFR, and angiogenesis markers (Factor VIII, CD31, and CD34) expression were significantly lower in the PTX-NPs group compared with other groups (p < .05). Also, PTX-NPs induced oxidative and nitrosative stress in tumor tissue. Direct administration of PTX-loaded polymeric nanoparticles based on α-Tocopheryl Succinate at the tumor sites, proved to be promising for HNSCC therapy.

Long-term follow-up of olfactory and gustatory dysfunction in COVID-19: 6 months case-control study of health workers.

PURPOSE: The study aimed to determine the incidence and long-term evolution of COVID-related olfactory (OD) and gustatory (GD) dysfunction, the recovery timeline, and the association with other symptoms. The secondary objective was to identify the predictive clinical factors for the evolution of these symptoms. METHODS: A prospective case-control study was conducted from March 15 to October 15, 2020, in health workers with COVID-19 related symptoms in a tertiary care hospital. 320 patients were included after 6 months of follow-up: 195 in the case group and 125 in the control group. Olfactory dysfunction (OD), dysosmia, and gustatory dysfunction (GD) onset and recovery rate after 6 months follow-up are analyzed in both groups. RESULTS: There were 125 (64.1%) in case group patients with OD and 118 (60.5%) with GD. Total or partial recovery OD and GD was found in 89%, mainly in the first 2 months. In the control group, there were 14 (11.2%) patients with OD and 33 (26.4%) patients with GD, with 100% of total/partial recovery. CONCLUSION: In both groups, OD and GD showed high-resolution rates during the first two months after the onset of symptoms. Nevertheless, 11% of the case group patients did not show any recovery, and the partial resolution was present in 30% of our patients, at the 6 months follow-up. We found a high correlation between OD and GD, both in the appearance of symptoms and in their recovery. Nasal obstruction and dyspnea have been identified as risk factors for the persistence of symptoms.

Safety and Prognosis in Percutaneous vs Surgical Tracheostomy in 27 Patients With COVID-19.

During the SARS-CoV-2 pandemic, patients in intensive care units who are undergoing long-term intubation may require tracheostomy. There is controversy about indication and health care professionals' safety regarding the conventional or percutaneous technique. We performed a prospective analysis of a series of 27 consecutive patients with COVID-19 comparing both tracheostomy techniques, safety, and prognosis clinical markers. The results show that the techniques are equally safe, without cases of infection in surgeons. The Sequential Organ Failure Assessment score before surgery and the progression in ventilation support during the first 72 hours after tracheostomy are optimal prognostic markers for these patients.

Polyphenols protect against age-associated apoptosis in female rat cochleae.

Dietary antioxidants, polyphenols, have been found to be beneficial in protecting against the generation of oxidative stress in various diseases associated with aging. Age-related hearing loss (AHL) is the number one neurodegenerative disorder on our aged population. Sprague-Dawley rats divided into five groups according to their age (3, 6, 12, 18 and 24 months old) and treated with 100 mg/day/kg body weight of polyphenols were used. Then, cochleae were harvested to measure caspase activities (- 3, - 8 and - 9), caspase-3 gene expression, ATP levels, Bax, BcL-2 and p53 levels. 8-OHdG levels (marker of DNA oxidative damage) and annexin-V were also measured in cochleae. Increased levels of caspase-3 and 9 in cochlea were observed with age and this effect was attenuated by polyphenol treatment. In addition, ATP and Bcl-2 levels in older rats were recovered after administration of polyphenols, while Bax and p53 levels protein decreased. Oral supplementation with polyphenols also reduces DNA oxidative damage of cochlear cell. Treatment with polyphenols inhibits the activation of age-related apoptotic signaling by decreasing oxidative stress inside the rat cochlea.

BCG immune activation reduces growth and angiogenesis in an in vitro model of head and neck squamous cell carcinoma.

Head and neck squamous cell carcinoma (HNSCC) is one of the most frequent cancers worldwide and is associated with poor survival and significant treatment morbidity. The immune profile in patients with HNSCC is immunosuppressive and presents cytokine-mediated adaptive immune responses, triggered apoptosis of T cells, and alterations in antigen processing machinery. Bacille Calmette-Guerin (BCG) immunotherapy has been used successfully as a treatment for several types of cancer. In the present study, we sought to determine the antitumor effect of soluble mediators from peripheral blood mononuclear immune cells (PBMCs) activated with BCG vaccine in a three-dimensional coculture model of HNSCC growth using FaDu hypopharynx carcinoma squamous cells. BCG activation of PBMCs led to an increase in CD4+ and CD8+ lymphocyte subsets concomitant with an elevation in the levels of the antitumor cytokines IL-6, TNF-α and IFN-γ, and a EGFR in FaDu cells. In addition, coculture with BCG-activated PBMCs reduced FaDu proliferation and increased cytotoxicity and apoptosis in parallel with an increase in caspase-3 activity and p53 expression. Finally, conditioned medium from BCG-activated PBMCs reduced the levels of the angiogenic factors vascular endothelial growth factor and angiopoietin-2 produced by human aortic endothelial cells (HAECs), and inhibited their proliferation and differentiation into capillary-like structures. Taken together, these results demonstrate that BCG vaccination induces antitumor responses in an HNSCC in vitro model and suggest that the BCG vaccine could be an effective alternative therapy for the treatment of HNSCC.

Mitochondrially Targeted Nanoparticles Based on α-TOS for the Selective Cancer Treatment.

The aim of this work is the preparation of an active nanovehicle for the effective administration of α-tocopheryl succinate (α-TOS). α-TOS is loaded in the core of nanoparticles (NPs) based on amphiphilic pseudo-block copolymers of N-vinyl pyrrolidone and a methacrylic derivative of α-TOS. These well-defined spherical NPs have sizes below 165 nm and high encapsulation efficiencies. In vitro activity of NPs is tested in hypopharynx squamous carcinoma (FaDu) cells and nonmalignant epithelial cells, demonstrating that the presence of additional α-TOS significantly enhances its antiproliferative activity; however, a range of selective concentrations is observed. These NPs induce apoptosis of FaDu cells by activating the mitochondria death pathway (via caspase-9). Both loaded and unloaded NPs act via complex II and produce high levels of reactive oxygen species that trigger apoptosis. Additionally, these NPs effectively suppress the vascular endothelial growth factor (VEGF) expression of human umbilical vein endothelial cells (HUVECs). These results open the possibility to use this promising nanoformulation as an α-TOS delivery system for the effective cancer treatment, effectively resolving the current limitations of free α-TOS administration.