Position paper on olfactory dysfunction: 2023

BACKGROUND: Since publication of the original Position Paper on Olfactory Dysfunction in 2017 (PPOD-17), the personal and societal burden of olfactory disorders has come sharply into focus through the lens of the COVID-19 pandemic. Clinicians, scientists and the public are now more aware of the importance of olfaction, and the impact of its dysfunction on quality of life, nutrition, social relationships and mental health. Accordingly, new basic, translational and clinical research has resulted in significant progress since the PPOD-17. In this updated document, we present and discuss currently available evidence for the diagnosis and management of olfactory dysfunction. Major updates to the current version include, amongst others: new recommendations on olfactory related terminology; new imaging recommendations; new sections on qualitative OD and COVID-19 OD; updated management section. Recommendations were agreed by all co-authors using a modified Delphi process. CONCLUSIONS: We have provided an overview of current evidence and expert-agreed recommendations for the definition, investigation, and management of OD. As for our original Position Paper, we hope that this updated document will encourage clinicians and researchers to adopt a common language, and in so doing, increase the methodological quality, consistency, and generalisability of work in this field.

Developing a core outcome set for clinical trials in olfactory disorders: a COMET initiative.

STATEMENT OF PROBLEM: Evaluating the effectiveness of the management of Olfactory Dysfunction (OD) has been limited by a paucity of high-quality randomised and/or controlled trials. A major barrier is heterogeneity of outcomes in such studies. Core outcome sets (COS) - standardized sets of outcomes that should be measured/reported as determined by consensus-would help overcome this problem and facilitate future meta-analyses and/or systematic reviews (SRs). We set out to develop a COS for interventions for patients with OD. METHODS: A long-list of potential outcomes was identified by a steering group utilising a literature review, thematic analysis of a wide range of stakeholders' views and systematic analysis of currently available Patient Reported Outcome Measures (PROMs). A subsequent e-Delphi process allowed patients and healthcare practitioners to individually rate the outcomes in terms of importance on a 9-point Likert scale. RESULTS: After 2 rounds of the iterative eDelphi process, the initial outcomes were distilled down to a final COS including subjective questions (visual analogue scores, quantitative and qualitative), quality of life measures, psychophysical testing of smell, baseline psychophysical testing of taste, and presence of side effects along with the investigational medicine/device and patient's symptom log. CONCLUSIONS: Inclusion of these core outcomes in future trials will increase the value of research on clinical interventions for OD. We include recommendations regarding the outcomes that should be measured, although future work will be required to further develop and revalidate existing outcome measures.

Hedonic perception of odors in children aged 5-8 years is similar across 18 countries: Preliminary data.

OBJECTIVE: Olfactory preference emerges very early in life, and the sense of smell in children rapidly develops until the second decade of life. It is still unclear whether hedonic perception of odors is shared in children inhabiting different regions of the globe. METHODS: Five-hundred ten healthy children (N = 510; ngirls = 256; nboys = 254) aged from 5 to 8 years from 18 countries rated the pleasantness of 17 odors. RESULTS: The hedonic perception of odors in children aged between 5 and 8 years was rather consistent across 18 countries and mainly driven by the qualities of an odor and the overall ability of children to label odorants. CONCLUSION: Conclusions from this study, being a secondary analysis, are limited to the presented set of odors that were initially selected for the development of U-Sniff test and present null findings for the cross-cultural variability in hedonic perception of odors across 18 countries. These two major issues should be addressed in the future to either contradict or replicate the results presented herewith. This research lays fundament for posing further research questions about the developmental aspects of hedonic perception of odors and opens a new door for investigating cross-cultural differences in chemosensory perception of children.

Selective Ion Acceleration by Intense Radiation Pressure.

We report on the selective acceleration of carbon ions during the interaction of ultrashort, circularly polarized and contrast-enhanced laser pulses, at a peak intensity of 5.5×10^{20} W/cm^{2}, with ultrathin carbon foils. Under optimized conditions, energies per nucleon of the bulk carbon ions reached significantly higher values than the energies of contaminant protons (33 MeV/nucleon vs 18 MeV), unlike what is typically observed in laser-foil acceleration experiments. Experimental data, and supporting simulations, emphasize different dominant acceleration mechanisms for the two ion species and highlight an (intensity dependent) optimum thickness for radiation pressure acceleration; it is suggested that the preceding laser energy reaching the target before the main pulse arrives plays a key role in a preferential acceleration of the heavier ion species.

Ureteral access sheath-related injuries vs. post-operative infections. Is sheath insertion always needed? A prospective randomized study to understand the lights and shadows of this practice.

OBJECTIVE: To compare intraoperative ureteral injuries in RIRS with UAS insertion with the rate of postoperative infections after RIRS without UAS insertion. PATIENTS AND METHODS: In this randomized trial, patients who received an indication for RIRS between January 2017 and December 2017 were divided into two groups. Group A had no UAS insertion and Group B had UAS insertion. Post-Ureteroscopic Lesion Scale (PULS) grading was performed after UAS or flexible ureteroscope removal. Proximal, middle and distal ureteral lesions were evaluated and compared according to the PULS scale. Additionally, patients in both groups were followed postoperatively to assess any infective complication. RESULTS: The evaluation comprised 181 patients, 89 for group A and 92 for group B. Overall stone-free rate, clinically insignificant residual fragments, and final stone-free rate were 41.4%, 53.5%, and 95%, respectively. There were 33 (37.1%) patients with ureteral lesions in group A while 42 (45.6%) patients had ureteral lesions in group B, with no significant difference. On the other hand, the overall presence of postoperative infection rate was much higher for Group A (37.1% vs 16.3% P = 0.03). CONCLUSIONS: UAS insertion does not result in a higher number of ureteral injuries. UAS insertion during RIRS allows a lower rate of postoperative infections. CLINICAL TRIAL REGISTRATION NUMBER (ISRCTN REGISTRY NUMBER): 55546280.

Ureteral access sheath-related injuries vs. post-operative infections. Is sheath insertion always needed? A prospective randomized study to understand the lights and shadows of this practice. / Lesiones relacionadas con la vaina de acceso ureteral frente a infecciones postoperatorias. ¿Es siempre necesaria la inserción de la vaina de acceso? Estudio prospectivo aleatorizado para comprender las luces y sombras de esta práctica.

OBJECTIVE: To compare intraoperative ureteral injuries in RIRS with UAS insertion with the rate of postoperative infections after RIRS without UAS insertion. PATIENTS AND METHODS: In this randomized trial, patients who received an indication for RIRS between January 2017 and December 2017 were divided into two groups. Group A had no UAS insertion and Group B had UAS insertion. Post-Ureteroscopic Lesion Scale (PULS) grading was performed after UAS or flexible ureteroscope removal. Proximal, middle and distal ureteral lesions were evaluated and compared according to the PULS scale. Additionally, patients in both groups were followed postoperatively to assess any infective complication. RESULTS: The evaluation comprised 181 patients, 89 for group A and 92 for group B. Overall stone-free rate, clinically insignificant residual fragments, and final stone-free rate were 41.4%, 53.5%, and 95%, respectively. There were 33 (37.1%) patients with ureteral lesions in group A while 42 (45.6%) patients had ureteral lesions in group B, with no significant difference. On the other hand, the overall presence of postoperative infection rate was much higher for Group A (37.1% vs 16.3% P=.03). CONCLUSIONS: UAS insertion does not result in a higher number of ureteral injuries. UAS insertion during RIRS allows a lower rate of postoperative infections. Clinical Trial Registration Number (ISRCTN registry number): 55546280.

Ultrashort high energy electron bunches from tunable surface plasma waves driven with laser wavefront rotation.

We propose to use ultrahigh intensity laser pulses with wave-front rotation (WFR) to produce short, ultraintense surface plasma waves (SPW) on grating targets for electron acceleration. Combining a smart grating design with optimal WFR conditions identified through simple analytical modeling and particle-in-cell simulation allows us to decrease the SPW duration (down to a few optical cycles) and increase its peak amplitude. In the relativistic regime, for Iλ_{0}^{2}=3.4×10^{19}W/cm^{2}µm^{2}, such SPW are found to accelerate high charge (few 10 s of pC), high energy (up to 70 MeV), and ultrashort (few fs) electron bunches.

Extreme Ultraviolet Beam Enhancement by Relativistic Surface Plasmons.

The emission of high-order harmonics in the extreme ultraviolet range from the interaction of a short, intense laser pulse with a grating target is investigated experimentally. When resonantly exciting a surface plasmon, both the intensity and the highest order observed for the harmonic emission along the grating surface increase with respect to a flat target. Harmonics are obtained when a suitable density gradient is preformed at the target surface, demonstrating the possibility to manipulate the grating profile on a nanometric scale without preventing the surface plasmon excitation. In support of this, the harmonic emission is spatiotemporally correlated to the acceleration of multi-MeV electron bunches along the grating surface. Particle-in-cell simulations reproduce the experimental results and give insight on the mechanism of high harmonic generation in the presence of surface plasmons.

Surgical correction of Peyronie's disease via tunica albuginea plication: long-term follow-up.

Peyronie's disease (PD) is an acquired connective tissue disorder of the tunica albuginea with fibrosis and inflammation that lead to palpable plaques formation, penile curvature, and pain during erection. Patients report negative effects on main domains such as physical appearance and self-image, sexual function, and performance. The aim of this study was to evaluate plication of the albuginea outcomes after a long-term follow-up period. Between 1998 and 2006, a total of 204 patients with PD underwent surgical correction with albuginea plication technique. We obtained complete long-term follow-up data in 187 cases. The follow-up data included evaluation of curvature correction, penile shortening, sexual function, complications, and patient satisfaction. After a mean follow-up of 141 months, the most common postoperative complications were: loss of length (150 patients had a minimal penile shortening ≤1.5 cm, 37 patient between 1.5, and 3 cm, none >3 cm), recurrent or residual penile curvature (15 patients, without impairing sexual intercourse), erectile dysfunction (15 patients had IIEF-5 < 10 at 5 years of follow-up vs. 28 patients at 10 years), change in penile sensation (37 patients experienced paresthesia of the glans 1 year after surgery, 28 at 5 years, and 15 at 10 years); painful or palpable suture knots (in 20 cases) spontaneously healed in 3 months. Overall, 77% of the patients and partners were completely satisfied, 14% partially satisfied, and 9% unsatisfied. Plication procedure is safe and simple to be performed compared with the classical Nesbit's procedure. It has a shorter surgical time, lower costs, and could be successfully performed by less experienced surgeons too. It has a minimal risk of de novo erectile dysfunction, injury to the dorsal neurovascular bundle. Results are good in terms of patient satisfaction according to anatomical outcome and functional correction.

Polarization Dependence of Bulk Ion Acceleration from Ultrathin Foils Irradiated by High-Intensity Ultrashort Laser Pulses.

The acceleration of ions from ultrathin (10-100 nm) carbon foils has been investigated using intense (∼6×10^{20} W cm^{-2}) ultrashort (45 fs) laser pulses, highlighting a strong dependence of the ion beam parameters on the laser polarization, with circularly polarized (CP) pulses producing the highest energies for both protons and carbons (25-30 MeV/nucleon); in particular, carbon ion energies obtained employing CP pulses were significantly higher (∼2.5 times) than for irradiations employing linearly polarized pulses. Particle-in-cell simulations indicate that radiation pressure acceleration becomes the dominant mechanism for the thinnest targets and CP pulses.

Efficient post-acceleration of protons in helical coil targets driven by sub-ps laser pulses.

The characteristics of laser driven proton beams can be efficiently controlled and optimised by employing a recently developed helical coil technique, which exploits the transient self-charging of solid targets irradiated by intense laser pulses. Here we demonstrate a well collimated (<1° divergence) and narrow bandwidth (~10% energy spread) proton beamlet of ~107 particles at 10 ± 0.5 MeV obtained by irradiating helical coil targets with a few joules, sub-ps laser pulses at an intensity of ~2 × 1019 W cm-2. The experimental data are in good agreement with particle tracing simulations suggesting post-acceleration of protons inside the coil at a rate ~0.7 MeV/mm, which is comparable to the results obtained from a similar coil target irradiated by a fs class laser at an order of magnitude higher intensity, as reported in S. Kar et al., Nat. Commun, 7, 10792 (2016). The dynamics of hot electron escape from the laser irradiated target was studied numerically for these two irradiation regimes, which shows that the target self-charging can be optimised at a pulse duration of few hundreds of fs. This information is highly beneficial for maximising the post-acceleration gradient in future experiments.

Electron Weibel instability in relativistic counterstreaming plasmas with flow-aligned external magnetic fields.

The Weibel instability driven by two symmetric counterstreaming relativistic electron plasmas, also referred to as current-filamentation instability, is studied in a constant and uniform external magnetic field aligned with the plasma flows. Both the linear and nonlinear stages of the instability are investigated using analytical modeling and particle-in-cell simulations. While previous studies have already described the stabilizing effect of the magnetic field, we show here that the saturation stage is only weakly affected. The different mechanisms responsible for the saturation are discussed in detail in the relativistic cold fluid framework considering a single unstable mode. The application of an external field leads to a slight increase of the saturation level for large wavelengths, while it does not affect the small wavelengths. Multimode and temperature effects are then investigated. While at high temperature the saturation level is independent of the external magnetic field, at low but finite temperature the competition between different modes in the presence of an external magnetic field leads to a saturation level lower with respect to the unmagnetized case.

Adjuvant treatment with a symbiotic in patients with inflammatory non-allergic rhinitis.

Inflammatory non-allergic rhinitis (INAR) is characterized by the presence of an inflammatory infiltrate and a non-IgE-mediated pathogenesis. This retrospective, controlled, multicentre study investigated whether a symbiotic, containing Lactobacillus acidophilus NCFM, Bifidobacterium lactis, and fructo-oligosaccharides (Pollagen®, Allergy Therapeutics, Italy), prescribed as adjunctive therapy to a standard pharmacological treatment, was able to reduce symptom severity, endoscopic features, and nasal cytology in 93 patients (49 males and 44 females, mean age 36.3±7.1 years) with INAR. The patients were treated with nasal corticosteroid, oral antihistamine, and isotonic saline. At randomization, 52 patients were treated also with symbiotic as adjunctive therapy, whereas the remaining 41 patients served as controls. Treatment lasted for 4 weeks. Patients were visited at baseline, after treatment, and after 4-week follow-up. Adjunctive symbiotic treatment significantly reduced the percentages of patients with symptoms and endoscopic signs, and diminished inflammatory cells. In conclusion, the present study demonstrates that a symbiotic was able, as adjuvant treatment, to significantly improve symptoms, endoscopic feature, and cytology in patients with INAR, and its effect may be long lasting.

Position paper on olfactory dysfunction.

Background: Olfactory dysfunction is an increasingly recognised condition, associated with reduced quality of life and major health outcomes such as neurodegeneration and death. However, translational research in this field is limited by heterogeneity in methodological approach, including definitions of impairment, improvement and appropriate assessment techniques. Accordingly, effective treatments for smell loss are limited. In an effort to encourage high quality and comparable work in this field, among others, we propose the following ideas and recommendations. Whilst the full set of recommendations are outlined in the main document, points include the following: • Patients with suspected olfactory loss should undergo a full examination of the head and neck, including rigid nasal endoscopy with small diameter endoscopes. • Subjective olfactory assessment should not be undertaken in isolation, given its poor reliability. • Psychophysical assessment tools used in clinical and research settings should include reliable and validated tests of odour threshold, and/or one of odour identification or discrimination. • Comprehensive chemosensory assessment should include gustatory screening. • Smell training can be helpful in patients with olfactory loss of several aetiologies. Conclusions: We hope the current manuscript will encourage clinicians and researchers to adopt a common language, and in so doing, increase the methodological quality, consistency and generalisability of work in this field.

Radiation-pressure-driven ion Weibel instability and collisionless shocks.

The Weibel instability from counterstreaming plasma flows is a basic process highly relevant for collisionless shock formation in astrophysics. In this paper we investigate, via two- and three-dimensional simulations, suitable configurations for laboratory investigations of the ion Weibel instability (IWI) driven by a fast quasineutral plasma flow launched into the target via the radiation pressure of an ultra-high-intensity laser pulse ("hole-boring" process). The use of S-polarized light at oblique incidence is found to be an optimal configuration for driving IWI, as it prevents the development of surface rippling observed at normal incidence that would lead to strong electron heating and would favor competing instabilities. Conditions for the evolution of IWI into a collisionless shock are also investigated.

Intranasal T-LysYal® as adjunctive therapy for patients after functional endoscopic sinus surgery.

Functional Endoscopic Sinus Surgery (FESS) is a common day surgery technique for upper airway disorders. Hyaluronic acid (HA) is a fundamental component of the human connective tissue. HA may exert reparative, anti-inflammatory and immune-modulating activities. Recently, a new intranasal HA formulation has been proposed: a supramolecular system containing lysine hyaluronate, thymine and sodium chloride (T-LysYal®). This randomized study investigated whether intranasal T-LysYal® (RinoLysYal®, Farmigea, Italy) was able to reduce symptom severity, endoscopic features, and nasal cytology in 83 patients (49 males and 34 females mean age 45.4±6.2 years) treated with FESS. All patients were treated with isotonic saline solution for 4 weeks, and a sub-group (active group) was also treated with intranasal T-LysYal®. Patients were visited at baseline, after treatment, and after 4-week follow-up. Intranasal T-LysYal® treatment significantly reduced the quote of patients with symptoms, endoscopic features, and inflammatory cells in comparison to isotonic solution. In conclusion, the present study demonstrates that intranasal T-LysYal® is able to significantly improve patients after FESS and its effect is long lasting.

Electron Acceleration by Relativistic Surface Plasmons in Laser-Grating Interaction.

The generation of energetic electron bunches by the interaction of a short, ultraintense (I>10(19) W/cm(2)) laser pulse with "grating" targets has been investigated in a regime of ultrahigh pulse-to-prepulse contrast (10(12)). For incidence angles close to the resonant condition for surface plasmon excitation, a strong electron emission was observed within a narrow cone along the target surface, with energy spectra peaking at 5-8 MeV and total charge of ∼100 pC. Both the energy and the number of emitted electrons were strongly enhanced with respect to simple flat targets. The experimental data are closely reproduced by three-dimensional particle-in-cell simulations, which provide evidence for the generation of relativistic surface plasmons and for their role in driving the acceleration process. Besides the possible applications of the scheme as a compact, ultrashort source of MeV electrons, these results are a step forward in the development of high-field plasmonics.

Position paper on olfactory dysfunction.

BACKGROUND: Olfactory dysfunction is an increasingly recognised condition, associated with reduced quality of life and major health outcomes such as neurodegeneration and death. However, translational research in this field is limited by heterogeneity in methodological approach, including definitions of impairment, improvement and appropriate assessment techniques. Accordingly, effective treatments for smell loss are limited. In an effort to encourage high quality and comparable work in this field, among others, we propose the following ideas and recommendations. Whilst the full set of recommendations are outlined in the main document, points include the following: - Patients with suspected olfactory loss should undergo a full examination of the head and neck, including rigid nasal endoscopy with small diameter endoscopes. - Subjective olfactory assessment should not be undertaken in isolation, given its poor reliability. - Psychophysical assessment tools used in clinical and research settings should include reliable and validated tests of odour threshold, and/or one of odour identification or discrimination. - Comprehensive chemosensory assessment should include gustatory screening. - Smell training can be helpful in patients with olfactory loss of several aetiologies. CONCLUSIONS: We hope the current manuscript will encourage clinicians and researchers to adopt a common language, and in so doing, increase the methodological quality, consistency and generalisability of work in this field.

Laser-driven Rayleigh-Taylor instability: plasmonic effects and three-dimensional structures.

The acceleration of dense targets driven by the radiation pressure of high-intensity lasers leads to a Rayleigh-Taylor instability (RTI) with rippling of the interaction surface. Using a simple model it is shown that the self-consistent modulation of the radiation pressure caused by a sinusoidal rippling affects substantially the wave vector spectrum of the RTI, depending on the laser polarization. The plasmonic enhancement of the local field when the rippling period is close to a laser wavelength sets the dominant RTI scale. The nonlinear evolution is investigated by three-dimensional simulations, which show the formation of stable structures with "wallpaper" symmetry.