The Value of Subjective Olfactometry as a Predictive Biomarker of Neurodegenerative Diseases: A Systematic Review.

BACKGROUND: Olfactory disorders (ODs) are reported to be an early non-motor sign before the onset of deterioration in neurodegenerative diseases (NDs) such as Alzheimer's and Parkinson's. This systematic revision aims to review the current literature and the value of subjective olfactometry (SO) in the early diagnosis of cognitive decline and NDs. METHODS: A systematic literature review was conducted following the PRISMA framework. Four different authors reviewed six different databases. The main variables analyzed were olfactory function and cognitive status. The quality of results was evaluated using the Oxford Centre of Evidence-based Medicine Levels. RESULTS: Twenty-one cross-sectional and cohort studies and six meta-analyses were included. Most of them found an association between ODs and NDs. A prevalence of ODs greater than 80% was shown in Parkinson's disease, proportional to the severity of symptoms. In Alzheimer's, ODs were associated with early diagnosis and prognosis. All SO tests employed in the literature showed enough predictive value to correlate with early stages of cognitive decline. CONCLUSIONS: SO should be considered a pivotal tool when diagnosing NDs due to their association with early symptoms and prognosis. However, in the current literature, no firm consensus exists on the optimal SO tests and protocols that should be applied to the study of NDs, which prevents the interpretability and comparability of results among studies.

Long-Term Clinical Outcomes in Patients with Chronic Rhinosinusitis with Nasal Polyps Associated with Expanded Types of Endoscopic Sinus Surgery.

(1) Background: Surgical criteria for chronic rhinosinusitis with nasal polyps (CRSwNP) remain unresolved. This study addresses these discrepancies by comparing the clinical outcomes of expanded-functional endoscopic sinus surgeries (E-FESS) with more-limited FESS (L-FESS). (2) Methods: A database was analyzed retrospectively to compare surgical outcomes in CRSwNP patients who underwent E-FESS versus those subjected to L-FESS. Quality of life, endoscopic and radiological outcomes were compared at the baseline and two years after surgery. The clinical status of the responder was defined when a minimal clinically important difference of 12 points in SNOT-22 change was achieved. (3) Results: A total of 274 patients met the inclusion criteria and were analyzed; 111 underwent E-FESS and 163 were subjected to L-FESS. Both groups exhibited significant clinical improvements, although a greater magnitude of change in SNOT-22 (14.8 ± 4.8, p = 0.002) was shown after E-FESS. Higher significant improvements for endoscopic and radiological scores and lower surgical revision rates were also noted in the E-FESS group. (4) Conclusions: E-FESS provides better clinical outcomes and reduced revision surgery rates when compared to L-FESS in CRSwNP patients two years after surgery, irrespective of any comorbidity. Further randomized prospective studies are needed to comprehensively contrast these results.

Tissue-specific early and late activated lymphocytes immunophenotype in chronic rhinosinusitis with nasal polyps.

KEY POINTS: T-cell activation in patients with chronic rhinosinusitis with nasal polyps (CRSwNP) is enriched by late cytotoxic T cells. The proportion of early and intermediate activated cytotoxic T cells decreases in nasal polyps of patients with CRSwNP. Our results identify late activated cytotoxic T cells as potential biomarkers or therapeutic targets for patients with CRSwNP.

Improved quality of life in patients with chronic rhinosinusitis with nasal polyps associated with expanded types of endoscopic sinus surgery: A 2-year retrospective study.

KEY POINTS: Expanded types of functional endoscopic sinus surgery (FESS) significantly improve quality of life and reduce revision surgeries rates, supporting their early application for moderate-to-severe cases. Minimal clinically important difference may play as a crucial role in defining surgical treatment response (i.e., responder and super-responder conditions). Expanded FESS benefits patients with chronic rhinosinusitis with nasal polyps but more data are required to have a clearer understanding of its uses due to varied approaches and reported outcomes in the literature.

Effect of antihypertensive treatment on the quality of life of patients with chronic rhinosinusitis with nasal polyps.

AIM: Nasal polyposis (CRSwNP) shares type 2 inflammation biomarkers with asthma, allergy or arterial hypertension (AH), including periostin, a predictive marker of severity and post-surgical recurrence of polyposis. Antihypertensives have been shown to decrease periostin expression. We set out to evaluate the effect of antihypertensives on the quality of life of patients with CRSwNP. MATERIALS AND METHODS: Retrospective study of 43 patients with CRSwNP and ah with at least 1year of follow-up and antihypertensive treatment prescribed after the diagnosis of CRSwNP. Phenotypes were analyzed (F1: isolated CRSwNP; F2: CRSwNP with asthma and/or NERD) and aspects related to quality of life (SNOT-22), clinical severity (VAS), polypoid size (NPS), exacerbations and surgical needs after the initiation of antihypertensive treatment. RESULTS: The predominant phenotype was F1 (62.8%). The number of exacerbations was 19.2% for F1, compared to 31.3% for F2. 34.8% underwent surgery after the start of antihypertensive treatment (F1=27.9% and F2=6.97%). A significant reduction in polypoid size, SNOT22 (16.4±19.6 points), and VAS scales (p<.05) was obtained. CONCLUSIONS: polypoid size, and reduce the risk of postoperative recurrence.

Endoscopic Extended Sinus Surgery for Patients with Severe Chronic Rhinosinusitis with Nasal Polyps, the Choice of Mucoplasty: A Systematic Review.

PURPOSE OF REVIEW: The advances in the knowledge of the molecular basis of the inflammatory response in chronic rhinosinusitis with nasal polyps (CRSwNP) have led the management of these patients towards personalized and precision medicine. Surgery has been positioned as a suitable alternative in patients who do not achieve control with appropriate medical treatment, but polypoid recurrences remain a constraint. The emergence of new surgical approaches based on patient phenotyping and the poor disease control associated with type 2 inflammatory phenotype makes it necessary to review the role of personalized and precision surgery in managing the disease. RECENT FINDINGS: Surgical approaches based on wide resection of bony sinus structures and the treatment of mucosa lining the sinonasal cavity have been analyzed and compared with other techniques and seem to offer more favorable surgical outcomes and improved quality of life (QoL), in addition to lower relapse rates. The innovations with new complementary surgical techniques, such as reboot surgery adding an extended autologous mucosal graft from the nasal floor (mucoplasty), may benefit endoscopic and QoL outcomes in the most severe CRSwNP patients with type 2 phenotype. Using bilateral endonasal mucoplasty as a complementary technique to reboot surgery is a suitable technical choice that has improved short- and medium-term QoL and endoscopic outcomes for patients with severe CRSwNP. These results are likely due to a combination of the extension of reboot and the inherent inflammatory and healing properties of mucoplasty. We propose this technique as a valuable surgical resource, although more robust clinical studies are needed to evaluate its long-term benefits comprehensively.

Omalizumab Treatment in Uncontrolled Asthma and CRSwNP Patients, with Previous Endoscopic Sinus Surgery, to Improve Quality of Life and Endoscopic Outcomes: a Two-Year Real-Life Study.

PURPOSE OF REVIEW: Despite molecular underlying advances, limited and divergent data on monoclonal antibodies (mAb) therapy in chronic rhinosinusitis with nasal polyps (CRSwNP) make further analysis necessary. The objective of this study is to evaluate the effect of omalizumab as an adjunct to endoscopic sinus surgery (ESS) on the treatment of CRSwNP under real-life conditions. RECENT FINDINGS: Since the introduction of omalizumab, as the first biologic agent for the treatment of diseases such as severe allergic asthma, different studies have demonstrated an effect of omalizumab on CRSwNP, with significant improvements in sinonasal symptoms and endoscopic scores. The high efficacy derived from mAb therapy and the need for ESS prior to mAb recommended by guidelines, has led to compare both therapeutic alternatives, finding discrepancies in their effect on quality of life (QoL) and complementary tests outcomes. Patients with moderate-to-severe asthma with clinical criteria for omalizumab indication, and coexistent CRSwNP disease, were selected for a non-randomized interventional retrospective study into four treatment subgroups. Measures were analyzed and compared between groups and over time at the baseline, 16 weeks and 1 and 2 years after treatment. Omalizumab treatment in patients with previous ESS exhibited an earlier and more pronounced improvement in QoL, symptoms scale and endoscopic findings (nasal polyp score and the bilateral modified Lund-Kennedy) as early from week 16, which improvement persisted for 2 years. A greater mean improvement of 33.4 ± 6.5 (95% CI: 20.3-46.4; p < 0.001) points in sinonasal outcome test 22 (SNOT-22) was associated with ESS at week 16, against omalizumab effect (17.8 ± 7.6 [95% CI: 2.6-33.0]; p = 0.023). At year 2, an improvement in SNOT-22 of 62.6 ± 8.9 (95% CI: 48.4-84.1; p < 0.001) points was exclusively associated with omalizumab. Clinical evidence of the effect of omalizumab added to ESS treatment is provided in this study in the short- and long-term.

Endoscopic-assisted en-bloc pterygomaxillectomy: Identifying an efficient and safe location for the pterygoid osteotomy.

BACKGROUND: For aggressive maxillary sinus and pterygopalatine fossa (PPF) tumors, an en-bloc pterygomaxillectomy may be indicated. METHODS: Five head specimens were used to study the feasibility of an en-bloc pterygomaxillectomy. Eighty-five non-pathological CT scans were used to compare the superior edge of the inferior turbinate (IT) and the middle turbinate tail (MT) as landmarks for the pterygoid osteotomy. RESULTS: Through a combined sublabial-subperiosteal incision and transoral route, a mid-sagittal osteotomy through the hard palate and an axial osteotomy below the infraorbital foramen were performed. For the endoscopic pterygoid osteotomy, an infra-vidian transpterygoid approach was performed, subsequently removing the pterygomaxillectomy en-bloc. As landmarks, the osteotomies at the level of the MT tail and IT resected the pterygoid plates completely, but the IT osteotomy was further away from the vidian canal (7.5 vs. 6 mm). CONCLUSIONS: The endoscopic-assisted en-bloc pterygomaxillectomy is feasible. The IT landmark is safe and ensures complete resection of the pterygoid plates.

Unidad de Atención al Paciente Traqueostomizado. Una solución innovadora desde Otorrinolaringología con carácter transversal para el hospital / Tracheostomy Patient Care Unit. An innovative Otorhinolaryngology solution of a transversal nature for the hospital

Antecedentes y objetivo: Los cuidados de los pacientes traqueostomizados son habilidades de alto riesgo y baja incidencia. Las estrategias de mejora de la atención sanitaria en plantas hospitalarias y en especialidades distintas a la Otorrinolaringología (ORL) basadas únicamente en la formación no han sido capaces de ofrecer una solución adecuada. Se presenta un modelo de Unidad de Atención al Paciente Traqueostomizado dirigida por el Servicio de Otorrinolaringología para atender a todos los pacientes traqueostomizados de un hospital en todas las especialidades. Material y métodos Ámbito: hospital universitario público de tercer nivel con 876 camas de hospitalización y 30 camas de UCI para 481.296 habitantes. Modelo de Unidad: unidad transversal para el hospital proporcionando atención a todos los pacientes traqueostomizados, adultos y niños, de todas las especialidades, con dedicación del 50% de una enfermera de ORL de hospitalización que se desplaza hasta la cama de hospitalización de la especialidad de cada paciente y el 50% de otra enfermera de ORL de consultas externas para los pacientes ambulatorios, con la consultoría de un especialista en ORL y coordinación de la supervisora de ORL. Resultados Se atendió en la unidad a 572 pacientes entre 2016 y 2021, el 80% varones, con una media de edad de 63±14 años. Se atendieron 14,7±2 pacientes traqueostomizados diarios y 96±4 consultas por complicaciones anuales, elevándose hasta 19 pacientes traqueostomizados diarios en 2020 y 141±8,4 consultas por complicaciones en los años 2020 y 2021, durante la pandemia por COVID-19. Se redujo la estancia media de las especialidades no ORL en 13 días a lo largo de los 6 años del estudio, aumentando la satisfacción de los profesionales de ORL y de no ORL, y la satisfacción de los usuarios.... (AU)

Background and objective: The care of tracheostomized patients are high risk skills and low incidence. Strategies for improvement of health care in hospital wards and specialties other than otolaryngology based solely on training have not been able to offer an adequate solution. A tracheostomized patient unit is presented directed by the otolaryngology service to attend all tracheostomized hospitalized patients of all specialties. Material and methods Background: Third level public hospital with 876 hospitalization beds and 30 ICU beds for 481,296 inhabitants. Unit model: Transversal unit for the hospital providing attention to all tracheostomized patients, adults, and children, of all specialties, with dedication of 50% of a ENT nurse of hospitalization that moves to the hospitalization bed of the specialty of each patient and 50% of another office ENT nurse for ambulatory patients care, with the consultancy of an ENT specialist and coordinated by the ENT supervisor. Results 572 patients between 2016 and 2021, 80% men, aged 63±14 years, were attended in the unit. 14.7±2 tracheostomized patients daily and 96±4 complication annual consultations were attended, rising up to 19 tracheostomized patients daily by 2020 and 141±8.4 consultations by complications in 2020 and 2021, during the COVID-19 pandemic. The mean stay of the non-ENT specialties was reduced in 13 days, increasing the satisfaction of the ENT and non-ENT professionals and the satisfaction of the users. ... (AU)

Tracheostomy Patient Care Unit. An innovative Otorhinolaryngology solution of a transversal nature for the hospital.

BACKGROUND AND OBJECTIVE: The care of tracheostomized patients are high risk skills and low incidence. Strategies for improvement of health care in hospital wards and specialties other than otolaryngology based solely on training have not been able to offer an adequate solution. A tracheostomized patient unit is presented directed by the otolaryngology service to attend all tracheostomized hospitalised patients of all specialties. MATERIAL AND METHODS: Background: Third level public hospital with 876 hospitalisation beds and 30 ICU beds for 481,296 inhabitants. Unit model: Transversal unit for the hospital providing attention to all tracheostomized patients, adults, and children, of all specialties, with dedication of 50% of a ENT nurse of hospitalisation that moves to the hospitalisation bed of the specialty of each patient and 50% of another office ENT nurse for ambulatory patients care, with the consultancy of an ENT specialist and coordinated by the ENT supervisor. RESULTS: 572 patients between 2016 and 2021, 80% men, aged 63 ± 14 years, were attended in the Unit. 14.7 ± 2 tracheostomized patients daily and 96 ± 4 complication annual consultations were attended, rising up to 19 tracheostomized patients daily by 2020 and 141 ± 8.4 consultations by complications in 2020 and 2021, during the COVID-19 pandemic. The mean stay of the non-ENT specialties was reduced in 13 days, increasing the satisfaction of the ENT and non-ENT professionals and the satisfaction of the users. CONCLUSIONS: A Tracheostomized Patient Care Unit proactively directed from the Otorhinolaryngology Service to transversally care for all tracheostomized patients improves the quality of health care by reducing stay, complications, and emergencies. Improves the satisfaction of non-otolaryngological professionals by reducing the anxiety of facing care of patients who lack knowledge and experience and that of ENT specialists and nurses by reducing unplanned extemporaneous demands for care. Improves user satisfaction by perceiving adequate continuity of care. The Otorhinolaryngology Services provide their experience in the management of laryngectomized and tracheostomized patients and in teamwork with other specialists and professionals without the need to create new structures outside Otorhinolaryngology.

Positional End-Point Nystagmus during Positional Testing: Prevalence, Characteristics and Differences with Benign Paroxysmal Positional Vertigo.

BACKGROUND: Some individuals present positional end-point nystagmus when the Dix-Hallpike tests are performed on them if they unintentionally look towards the examined ear. OBJECTIVE: To describe the prevalence and the characteristics of end-point nystagmus during positional testing in healthy subjects. METHODS: Sixty healthy subjects were included. Eight positional tests were performed on them, two Pagnini-McClure tests and six Dix-Hallpike tests, while keeping the eyes in different positions; one on each side. Two independent observers filled in a questionnaire about the presence of positional nystagmus, its latency, duration, direction, and sense. RESULTS AND CONCLUSIONS: Of the subjects, 65% showed positional end-point nystagmus. This nystagmus had a short latency and last for as long as the head is maintained in the test position. They can show any direction or sense, but the most common are torsional clockwise in left tests and anticlockwise in right tests. Unlike BPPV, this nystagmus did not appear with the eyes in the straight-ahead position, it is asymptomatic, and its intensity does not decline.

Analysis of Prevalence and Predictive Factors of Long-Lasting Olfactory and Gustatory Dysfunction in COVID-19 Patients.

BACKGROUND: Although smell and taste disorders are highly prevalent symptoms of COVID-19 infection, the predictive factors leading to long-lasting chemosensory dysfunction are still poorly understood. METHODS: 102 out of 421 (24.2%) mildly symptomatic COVID-19 patients completed a second questionnaire about the evolution of their symptoms one year after the infection using visual analog scales (VAS). A subgroup of 69 patients also underwent psychophysical evaluation of olfactory function through UPSIT. RESULTS: The prevalence of chemosensory dysfunction decreased from 82.4% to 45.1% after 12 months, with 46.1% of patients reporting a complete recovery. Patients older than 40 years (OR = 0.20; 95% CI: [0.07, 0.56]) and with a duration of loss of smell longer than four weeks saw a lower odds ratio for recovery (OR = 0.27; 95% CI: [0.10, 0.76]). In addition, 28 patients (35.9%) reported suffering from parosmia, which was associated with moderate to severe taste dysfunction at the baseline (OR = 7.80; 95% CI: [1.70, 35.8]). Among the 69 subjects who underwent the UPSIT, 57 (82.6%) presented some degree of smell dysfunction, showing a moderate correlation with self-reported VAS (r = -0.36, p = 0.0027). CONCLUSION: A clinically relevant number of subjects reported persistent chemosensory dysfunction and parosmia one year after COVID-19 infection, with a moderate correlation with psychophysical olfactory tests.

Chemical bond imaging using torsional and flexural higher eigenmodes of qPlus sensors.

Non-contact atomic force microscopy (AFM) with CO-functionalized tips allows visualization of the chemical structure of adsorbed molecules and identify individual inter- and intramolecular bonds. This technique enables in-depth studies of on-surface reactions and self-assembly processes. Herein, we analyze the suitability of qPlus sensors, which are commonly used for such studies, for the application of modern multifrequency AFM techniques. Two different qPlus sensors were tested for submolecular resolution imaging via actuating torsional and flexural higher eigenmodes and via bimodal AFM. The torsional eigenmode of one of our sensors is perfectly suited for performing lateral force microscopy (LFM) with single bond resolution. The obtained LFM images agree well with images from the literature, which were scanned with customized qPlus sensors that were specifically designed for LFM. The advantage of using a torsional eigenmode is that the same molecule can be imaged either with a vertically or laterally oscillating tip without replacing the sensor simply by actuating a different eigenmode. Submolecular resolution is also achieved by actuating the 2nd flexural eigenmode of our second sensor. In this case, we observe particular contrast features that only appear in the AFM images of the 2nd flexural eigenmode but not for the fundamental eigenmode. With complementary laser Doppler vibrometry measurements and AFM simulations we can rationalize that these contrast features are caused by a diagonal (i.e. in-phase vertical and lateral) oscillation of the AFM tip.

Experimental analysis of tip vibrations at higher eigenmodes of QPlus sensors for atomic force microscopy.

QPlus sensors are non-contact atomic force microscope probes constructed from a quartz tuning fork and a tungsten wire with an electrochemically etched tip. These probes are self-sensing and offer an atomic-scale spatial resolution. Therefore, qPlus sensors are routinely used to visualize the chemical structure of adsorbed organic molecules via the so-called bond imaging technique. This is achieved by functionalizing the AFM tip with a single CO molecule and exciting the sensor at the first vertical cantilever resonance mode. Recent work using higher-order resonance modes has also resolved the chemical structure of single organic molecules. However, in these experiments, the image contrast can differ significantly from the conventional bond imaging contrast, which was suspected to be caused by unknown vibrations of the tip. This work investigates the source of these artefacts by using a combination of mechanical simulation and laser vibrometry to characterize a range of sensors with different tip wire geometries. The results show that increased tip mass and length cause increased torsional rotation of the tuning fork beam due to the off-center mounting of the tip wire, and increased flexural vibration of the tip. These undesirable motions cause lateral deflection of the probe tip as it approaches the sample, which is rationalized to be the cause of the different image contrast. The results also provide a guide for future probe development to reduce these issues.

Loss of Smell and Taste Can Accurately Predict COVID-19 Infection: A Machine-Learning Approach.

The COVID-19 outbreak has spread extensively around the world. Loss of smell and taste have emerged as main predictors for COVID-19. The objective of our study is to develop a comprehensive machine learning (ML) modelling framework to assess the predictive value of smell and taste disorders, along with other symptoms, in COVID-19 infection. A multicenter case-control study was performed, in which suspected cases for COVID-19, who were tested by real-time reverse-transcription polymerase chain reaction (RT-PCR), informed about the presence and severity of their symptoms using visual analog scales (VAS). ML algorithms were applied to the collected data to predict a COVID-19 diagnosis using a 50-fold cross-validation scheme by randomly splitting the patients in training (75%) and testing datasets (25%). A total of 777 patients were included. Loss of smell and taste were found to be the symptoms with higher odds ratios of 6.21 and 2.42 for COVID-19 positivity. The ML algorithms applied reached an average accuracy of 80%, a sensitivity of 82%, and a specificity of 78% when using VAS to predict a COVID-19 diagnosis. This study concludes that smell and taste disorders are accurate predictors, with ML algorithms constituting helpful tools for COVID-19 diagnostic prediction.

Surface-controlled reversal of the selectivity of halogen bonds.

Intermolecular halogen bonds are ideally suited for designing new molecular assemblies because of their strong directionality and the possibility of tuning the interactions by using different types of halogens or molecular moieties. Due to these unique properties of the halogen bonds, numerous areas of application have recently been identified and are still emerging. Here, we present an approach for controlling the 2D self-assembly process of organic molecules by adsorption to reactive vs. inert metal surfaces. Therewith, the order of halogen bond strengths that is known from gas phase or liquids can be reversed. Our approach relies on adjusting the molecular charge distribution, i.e., the σ-hole, by molecule-substrate interactions. The polarizability of the halogen and the reactiveness of the metal substrate are serving as control parameters. Our results establish the surface as a control knob for tuning molecular assemblies by reversing the selectivity of bonding sites, which is interesting for future applications.

On-Surface Synthesis and Characterization of a Cycloarene: C108 Graphene Ring.

The synthesis of cycloarenes in solution is challenging because of their low solubility and the often hindered cyclodehydrogenation reaction of their nonplanar precursors. Using an alternative on-surface synthesis protocol, we achieved an unprecedented double-stranded hexagonal cycloarene containing 108 sp2 carbon atoms. Its synthesis is based on hierarchical Ullmann coupling and cyclodehydrogenation of a specially designed precursor on a Au(111) surface. The structure and other properties of the cycloarene are investigated by scanning tunneling microscopy/spectroscopy, atomic force microscopy, and density functional theory calculations.