Search

In recent years, the field of epitranscriptomics has witnessed significant breakthroughs with the identification of more than 150 different chemical modifications in different RNA species. It has become increasingly clear that these chemical modifications play an important role in the regulation of fundamental processes linked to cell fate and development. Further interest was sparked by the ability of the epitranscriptome to regulate pathogenesis. However, despite the involvement of macrophages in a multitude of diseases, a clear knowledge gap exists in the understanding of how RNA modifications regulate the phenotype of these cells. Here, we provide a comprehensive overview of the known roles of macrophage RNA modifications in the context of different diseases., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 The Author(s). Published by Elsevier Inc. on behalf of The American Society of Gene and Cell Therapy.)

Background & Aims: Liver macrophages fulfill various homeostatic functions and represent an essential line of defense against pathogenic insults. However, it remains unclear whether a history of infectious disease in the liver leads to long-term alterations to the liver macrophage compartment., Methods: We utilized a curable model of parasitic infection invoked by the protozoan parasite Trypanosoma brucei brucei to investigate whether infection history can durably reshape hepatic macrophage identity and function. Employing a combination of fate mapping, single-cell CITE-sequencing, single-nuclei multiome analysis, epigenomic analysis, and functional assays, we studied the alterations to the liver macrophage compartment during and after the resolution of infection., Results: We show that T. brucei brucei infection alters the composition of liver-resident macrophages, leading to the infiltration of monocytes that differentiate into various infection-associated macrophage populations with divergent transcriptomic profiles. Whereas infection-associated macrophages disappear post-resolution of infection, monocyte-derived macrophages engraft in the liver, assume a Kupffer cell (KC)-like profile and co-exist with embryonic KCs in the long-term. Remarkably, the prior exposure to infection imprinted an altered transcriptional program on post-resolution KCs that was underpinned by an epigenetic remodeling of KC chromatin landscapes and a shift in KC ontogeny, along with transcriptional and epigenetic alterations in their niche cells. This reprogramming altered KC functions and was associated with increased resilience to a subsequent bacterial infection., Conclusion: Our study demonstrates that a prior exposure to a parasitic infection induces trained immunity in KCs, reshaping their identity and function in the long-term., Impact and Implications: Although the liver is frequently affected during infections, and despite housing a major population of resident macrophages known as Kupffer cells (KCs), it is currently unclear whether infections can durably alter KCs and their niche cells. Our study provides a comprehensive investigation into the long-term impact of a prior, cured parasitic infection, unveiling long-lasting ontogenic, epigenetic, transcriptomic and functional changes to KCs as well as KC niche cells, which may contribute to KC remodeling. Our data suggest that infection history may continuously reprogram KCs throughout life with potential implications for subsequent disease susceptibility in the liver, influencing preventive and therapeutic approaches., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Chronic rhinosinusitis (CRS) is a highly prevalent disease and up to 83% of CRS patients suffer from olfactory dysfunction (OD). Because OD is specifically seen in those CRS patients that present with a type 2 eosinophilic inflammation, it is believed that type 2 inflammatory mediators at the level of the olfactory epithelium are involved in the development of this olfactory loss. However, due to the difficulties in obtaining tissue from the olfactory epithelium, little is known about the true mechanisms of inflammatory OD. Thanks to the COVID-19 pandemic, interest in olfaction has been growing rapidly and several studies have been focusing on disease mechanisms of OD in inflammatory conditions. In this paper, we summarize the most recent data exploring the pathophysiological mechanisms underlying OD in CRS. We also review what is known about the potential capacity of olfactory recovery of the currently available treatments in those patients.

Objectives: Olfactory dysfunction (OD) is common and carries significant personal and societal burden. Accurate assessment is necessary for good clinical and research practice but is highly dependent on the assessment technique used. Current practice with regards to UK/international clinical assessment is unknown. We aimed to capture current clinical practice, with reference to contemporaneously available guidelines. We further aimed to compare UK to international practice., Design: Anonymous online questionnaire with cross-sectional non-probability sampling. Subgroup analysis according to subspeciality training in rhinology ('rhinologists' and 'non-rhinologists') was performed, with geographical comparisons only made according to subgroup., Participants: ENT surgeons who assess olfaction., Results: Responses were received from 465 clinicians (217 from UK and 17 countries total). Country-specific response rate varied, with the lowest rate being obtained from Japan (1.4%) and highest from Greece (72.5%). Most UK clinicians do not perform psychophysical smell testing during any of the presented clinical scenarios-though rhinologists did so more often than non-rhinologists. The most frequent barriers to testing related to service provision (e.g., time/funding limitations). Whilst there was variability in practice, in general, international respondents performed psychophysical testing more frequently than those from the UK. Approximately 3/4 of all respondents said they would like to receive training in psychophysical smell testing. Patient reported outcome measures were infrequently used in the UK/internationally. More UK respondents performed diagnostic MRI scanning than international respondents., Conclusions: To our knowledge, this is the most comprehensive UK-based, and only international survey of clinical practice in the assessment of OD. We present recommendations to improve practice, including increased education and funding for psychophysical smell testing. We hope this will promote accurate and reliable olfactory assessment, as is the accepted standard in other sensory systems., (© 2023 The Authors. Clinical Otolaryngology published by John Wiley & Sons Ltd.)

Synthetic organic polymers commonly are used in the construction of healthcare product and medical device components. Medical devices often are sterilized to ensure that they are free from viable microorganisms. A common technique to achieve this is using ionizing radiation, usually gamma. A trend exists in industrial sterilization to supplement gamma with alternative accelerator technologies (e.g., X-ray). In the current work, studies were performed to characterize polymer modifications caused by gamma and X-ray sterilization processes and to assess the comparative equivalency. The studies were developed to evaluate two key process parameters: dose and dose rate. Three commonly used polymers were selected: high-density polyethylene, low-density polyethylene, and polypropylene. Four grades of each family were chosen. The dose assessment involved sample exposures to both gamma and X-ray irradiation at two dose levels (30 and 55 kGy). All other processing conditions, including dose rate, were controlled at standard processing levels akin to each sterilization technology. The dose rate assessment expanded on each dose level by introducing two additional dose rate parameters. Subsequent laboratory testing used techniques to characterize physico-chemical properties of the polymers to ascertain equivalency across test groups. Initial results indicated positive levels of equivalency between gamma and X-ray irradiation.

Background: Decline in olfaction may occur after general anesthesia, but the exact incidence and underlying physiopathology remain scarcely investigated. Olfactory dysfunction arises with aging and is known to be linked to cognitive impairment. In this pilot study, we evaluated the incidence of immediate postoperative decline in olfaction and its association with a preoperative cognitive test, performance at Clock Drawing Test (CDT), in a group of older patients., Methods: This pilot study is a sub-analysis of a prospective observational study. Patients ≥ 65 years old and scheduled for elective non-cardiac surgery under sevoflurane-based anesthesia were enrolled. CDT was part of the preoperative evaluation. We assessed olfaction on the day before and the day after surgery (between 16 and 26 h postoperatively) using the Sniffin' Sticks 12-item identification test, which consists of pen-like devices displaying 12 different odors. Postoperative decline in olfaction was defined as a decrease of at least 1 standard deviation in the olfactory score., Results: We included a total of 93 patients, among whom 19 (20.4%) presented a postoperative decline in olfaction. The incidence of postoperative decline in olfaction was higher in the "CDT low-score" (score ≤ 5/8) group (11/34, 32.4%) than in the "CDT high-score" (score ≥ 6/8) group (8/58, 13.6%) (P = 0.030). Despite adjusting for confounding variables, CDT score remained independently associated with immediate postoperative decline in olfactory identification function (OR 0.67, 95% CI 0.48 to 0.94, P = 0.022)., Conclusions: Postoperative decline in olfaction occurred in 20.4% of older patients and was associated with poor preoperative performance at CDT., Trial Registration: This study was retrospectively registered on https://clinicaltrials.gov/ under the NCT04700891 number (principal investigator: Victoria Van Regemorter), in December 2020., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: Real-world evidence (RWE) is a valuable instrument to better understand the patient journey and effectiveness of therapies. RWE on the prevalence of uncontrolled chronic rhinosinusitis (CRS) and CRS natural course of disease across Europe is scarce. In addition, there is limited RWE that enables comparison of the effectiveness of marketed therapies including topical or systemic corticosteroids, sinus surgery, or biologics., Objective: To establish an international CHRonic rhINOSinusitis Outcome Registry (CHRINOSOR) based on real-world data collection enabled by mobile health technology., Methodology: A digital platform, Galenus Health, supporting patients and physicians in the management of chronic respiratory diseases, is used to collect data on patient profile, disease history, patient outcomes, and a set of relevant clinical outcomes. Adult patients with a diagnosis of CRS are eligible for inclusion., Results: A collaborative scientific network of 17 university ear-nose-throat (ENT) clinics from 10 European countries has been established with the aim to collect real-world data in a longitudinal and standardized manner. The Galenus Health digital platform is currently being implemented in these ENT clinics taking into account legal, privacy, and data security aspects. Up to 300 patients have already been included., Conclusions: CHRINOSOR is a collaborative effort that aims at improving our understanding of CRS, its comorbidities, and the effectiveness of its treatments. Ultimately, these insights will guide us as scientific community to develop future care pathways informed by RWE., (Copyright © 2022 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Definitions are essential for effective communication and discourse, particularly in science. They allow the shared understanding of a thought or idea, generalization of knowledge, and comparison across scientific investigation. The current terms describing olfactory dysfunction are vague and overlapping., Summary: As a group of clinical olfactory researchers, we propose the standardization of the terms "dysosmia," "anosmia," "hyposmia," "normosmia," "hyperosmia," "olfactory intolerance," "parosmia," and "phantosmia" (or "olfactory hallucination") in olfaction-related communication, with specific definitions in this text., Key Messages: The words included in this paper were determined as those which are most frequently used in the context of olfactory function and dysfunction, in both clinical and research settings. Despite widespread use in publications, however, there still exists some disagreement in the literature regarding the definitions of terms related to olfaction. Multiple overlapping and imprecise terms that are currently in use are confusing and hinder clarity and universal understanding of these concepts. There is a pressing need to have a unified agreement on the definitions of these olfactory terms by researchers working in the field of chemosensory sciences. With the increased interest in olfaction, precise use of these terms will improve the ability to integrate and advance knowledge in this field., (© 2023 The Author(s). Published by S. Karger AG, Basel.)

Cycling hypoxia (cyH), neo-angiogenesis, and tumor-associated macrophages are key features of the tumor microenvironment. In this study, we demonstrate that cyH potentiates the induction by unpolarized and M1-like macrophages of endothelial inflammatory phenotype and adhesiveness for monocytes and cancer cells. This process triggers a positive feedback loop sustaining tumor inflammation. This work opens the door for innovative therapeutic strategies to treat tumor inflammation and metastasis. In cancers, the interaction between macrophages and endothelial cells (ECs) regulates tumor inflammation and metastasis. These cells are both affected by cycling hypoxia (cyH), also called intermittent hypoxia, a feature of the tumor microenvironment. cyH is also known to favor tumor inflammation and metastasis. Nonetheless, the potential impact of cyH on the dialog between macrophages and ECs is still unknown. In this work, the effects of unpolarized, M1-like, and M2-like macrophages exposed to normoxia, chronic hypoxia (chH), and cyH on endothelial adhesion molecule expression, pro-inflammatory gene expression, and EC adhesiveness for monocytes and cancer cells were investigated. cyH increased the ability of unpolarized and M1-like macrophages to induce EC inflammation and to increase the expression of the EC endothelial adhesion molecule ICAM1, respectively. Unpolarized, M1-like, and M2-like macrophages were all able to promote EC adhesive properties toward cancer cells. Furthermore, the ability of macrophages (mostly M1-like) to shift EC phenotype toward one allowing cancer cell and monocyte adhesion onto ECs was potentiated by cyH. These effects were specific to cyH because they were not observed with chH. Together, these results show that cyH amplifies the effects of macrophages on ECs, which may promote tumor inflammation and metastasis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Delprat, Huart, Feron, Soncin and Michiels.)

Background: The literature regarding clinical olfaction, olfactory loss, and olfactory dysfunction has expanded rapidly over the past two decades, with an exponential rise in the past year. There is substantial variability in the quality of this literature and a need to consolidate and critically review the evidence. It is with that aim that we have gathered experts from around the world to produce this International Consensus on Allergy and Rhinology: Olfaction (ICAR:O)., Methods: Using previously described methodology, specific topics were developed relating to olfaction. Each topic was assigned a literature review, evidence-based review, or evidence-based review with recommendations format as dictated by available evidence and scope within the ICAR:O document. Following iterative reviews of each topic, the ICAR:O document was integrated and reviewed by all authors for final consensus., Results: The ICAR:O document reviews nearly 100 separate topics within the realm of olfaction, including diagnosis, epidemiology, disease burden, diagnosis, testing, etiology, treatment, and associated pathologies., Conclusion: This critical review of the existing clinical olfaction literature provides much needed insight and clarity into the evaluation, diagnosis, and treatment of patients with olfactory dysfunction, while also clearly delineating gaps in our knowledge and evidence base that we should investigate further., (© 2022 ARS-AAOA, LLC.)

Radiotherapy (RT) is a key component of cancer treatment. Although improvements have been made over the years, radioresistance remains a challenge. For this reason, a better understanding of cell fates in response to RT could improve therapeutic options to enhance cell death and reduce adverse effects. Here, we showed that combining RT (photons and protons) to noncytotoxic concentration of PARP inhibitor, Olaparib, induced a cell line-dependent senescence-like phenotype. The senescent cells were characterized by morphological changes, an increase in p21 mRNA expression as well as an increase in senescence-associated β-galactosidase activity. We demonstrated that these senescent cells could be specifically targeted by Navitoclax (ABT-263), a Bcl-2 family inhibitor. This senolytic drug led to significant cell death when combined with RT and Olaparib, while limited cytotoxicity was observed when used alone. These results demonstrate that a combination of RT with PARP inhibition and senolytics could be a promising therapeutic approach for cancer patients.

EPOS2020 is the 4th and most recent version of the European Position Paper on Rhinosinusitis and Nasal Polyps which was first published in 2005. It aims to provide the most up to date scientifically robust information on the topic published in the literature which has been critically analysed by an international group of clinicians drawn from all disciplines dealing with these problems together with patients. The guidelines offer evidence-based recommendations and care pathways for acute and chronic rhinosinusitis in both adults and children. Management of these diseases from the patients' perspective is an important part of EPOS2020. Not only is this included in the main document but, for the first time, we have produced a separate supplement dedicated to and in collaboration with patients, EPOS4Patients, which aims to provide information in an accessible format, to answer frequently asked questions about these diseases and their treatment options as well as including useful patient resources and websites. It has never been more important for patients to be actively involved in their care. Being well informed helps you to make the best decisions together with your doctor.

Adequate nasal breathing is indispensable for athletes, and nasal symptoms have been shown to interfere with their subjective feeling of comfortable breathing and quality of life. Nasal symptoms are caused by either structural abnormalities or mucosal pathology. Structural pathologies are managed differently from mucosal disease, and therefore, adequate diagnosis is of utmost importance in athletes in order to choose the correct treatment option for the individual. Literature suggests that nasal symptoms are more prevalent in athletes compared to the general population and certain sports environments might even trigger the development of symptoms. Given the high demands of respiratory function in athletes, insight into triggering factors is of high importance for disease prevention. Also, it has been suggested that athletes are more neglectful to their symptoms and hence remain undertreated, meaning that special attention should be paid to education of athletes and their caregivers. This review aims at giving an overview of nasal physiology in exercise as well as the possible types of nasal pathology. Additionally, diagnostic and treatment options are discussed and we focus on unmet needs for the management and prevention of these symptoms in athletes within the concept of precision medicine., (© 2021 European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

The frequent association between coronavirus disease 2019 (COVID-19) and olfactory dysfunction is creating an unprecedented demand for a treatment of the olfactory loss. Systemic corticosteroids have been considered as a therapeutic option. However, based on current literature, we call for caution using these treatments in early COVID-19-related olfactory dysfunction because: (1) evidence supporting their usefulness is weak; (2) the rate of spontaneous recovery of COVID-19-related olfactory dysfunction is high; and (3) corticosteroids have well-known potential adverse effects. We encourage randomized placebo-controlled trials investigating the efficacy of systemic steroids in this indication and strongly emphasize to initially consider smell training, which is supported by a robust evidence base and has no known side effects., (© 2021 ARS-AAOA, LLC.)

Objective/hypothesis: With the COVID-19 pandemic, chemosensory dysfunction are among the most prevalent symptoms. Most reports are subjective evaluations, which have been suggested to be unreliable. The objective is to test chemosensory dysfunction and recovery based on extensive psychophysical tests in COVID-19 during the course of the disease., Study Design: Prospective cohort study., Methods: A total of 111 patients from four centers participated in the study. All tested positive for SARS-COV-2 with RT-PCR. They were tested within 3 days of diagnosis and 28 to 169 days after infection. Testing included extensive olfactory testing with the Sniffin' Sticks test for threshold, discrimination and identification abilities, and with the Taste Sprays and Taste Strips for gustatory function for quasi-threshold and taste identification abilities., Results: There was a significant difference in olfactory function during and after infection. During infection 21% were anosmic, 49% hyposmic, and 30% normosmic. After infection only 1% were anosmic, 26% hyposmic, and 73% normosmic. For gustatory function, there was a difference for all taste qualities, but significantly in sour, bitter, and total score. Twenty-six percent had gustatory dysfunction during infection and 6.5% had gustatory dysfunction after infection. Combining all tests 22% had combined olfactory and gustatory dysfunction during infection. After infection no patients had combined dysfunction., Conclusions: Chemosensory dysfunction is very common in COVID-19, either as isolated smell or taste dysfunction or a combined dysfunction. Most people regain their chemosensory function within the first 28 days, but a quarter of the patients show persisting dysfunction, which should be referred to specialist smell and taste clinics for rehabilitation of chemosensory function., Level of Evidence: 3 Laryngoscope, 131:1095-1100, 2021., (© 2021 The Authors. The Laryngoscope published by Wiley Periodicals LLC on behalf of The American Laryngological, Rhinological and Otological Society, Inc.)

Background: Respiratory tract viruses are the second most common cause of olfactory dysfunction. As we learn more about the effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), with the recognition that olfactory dysfunction is a key symptom of this disease process, there is a greater need than ever for evidence-based management of postinfectious olfactory dysfunction (PIOD)., Objective: Our aim was to provide an evidence-based practical guide to the management of PIOD (including post-coronavirus 2019 cases) for both primary care practitioners and hospital specialists., Methods: A systematic review of the treatment options available for the management of PIOD was performed. The written systematic review was then circulated among the members of the Clinical Olfactory Working Group for their perusal before roundtable expert discussion of the treatment options. The group also undertook a survey to determine their current clinical practice with regard to treatment of PIOD., Results: The search resulted in 467 citations, of which 107 articles were fully reviewed and analyzed for eligibility; 40 citations fulfilled the inclusion criteria, 11 of which were randomized controlled trials. In total, 15 of the articles specifically looked at PIOD whereas the other 25 included other etiologies for olfactory dysfunction., Conclusions: The Clinical Olfactory Working Group members made an overwhelming recommendation for olfactory training; none recommended monocycline antibiotics. The diagnostic role of oral steroids was discussed; some group members were in favor of vitamin A drops. Further research is needed to confirm the place of other therapeutic options., (Copyright © 2021 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

In a preregistered, cross-sectional study, we investigated whether olfactory loss is a reliable predictor of COVID-19 using a crowdsourced questionnaire in 23 languages to assess symptoms in individuals self-reporting recent respiratory illness. We quantified changes in chemosensory abilities during the course of the respiratory illness using 0-100 visual analog scales (VAS) for participants reporting a positive (C19+; n = 4148) or negative (C19-; n = 546) COVID-19 laboratory test outcome. Logistic regression models identified univariate and multivariate predictors of COVID-19 status and post-COVID-19 olfactory recovery. Both C19+ and C19- groups exhibited smell loss, but it was significantly larger in C19+ participants (mean ± SD, C19+: -82.5 ± 27.2 points; C19-: -59.8 ± 37.7). Smell loss during illness was the best predictor of COVID-19 in both univariate and multivariate models (ROC AUC = 0.72). Additional variables provide negligible model improvement. VAS ratings of smell loss were more predictive than binary chemosensory yes/no-questions or other cardinal symptoms (e.g., fever). Olfactory recovery within 40 days of respiratory symptom onset was reported for ~50% of participants and was best predicted by time since respiratory symptom onset. We find that quantified smell loss is the best predictor of COVID-19 amongst those with symptoms of respiratory illness. To aid clinicians and contact tracers in identifying individuals with a high likelihood of having COVID-19, we propose a novel 0-10 scale to screen for recent olfactory loss, the ODoR-19. We find that numeric ratings ≤2 indicate high odds of symptomatic COVID-19 (4 < OR < 10). Once independently validated, this tool could be deployed when viral lab tests are impractical or unavailable., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

(1) Background: The influence of food culture on eating behavior and obesity risk is poorly understood. (2) Methods: In this qualitative study, 25 adults in France with or without overweight/obesity participated in semi-structured interviews ( n = 10) or focus groups ( n = 15) to examine attitudes to food consumption and external pressures that influence eating behavior and weight management. Results were compared to an equivalent study conducted in the United States, thereby contrasting two countries with markedly different rates of obesity. Emerging key themes in the French data were identified through coding using a reflexive approach. (3) Results: The main themes identified were: (1) influence of commensality, social interactions, and pleasure from eating on eating behavior, (2) having a balanced and holistic approach to nutrition, (3) the role of environmental concerns in food consumption, (4) relationship with "natural" products (idealized) and food processing (demonized), (5) perceptions of weight status and management. Stress and difficulties in hunger cue discernment were viewed as important obstacles to weight management in both countries. External pressures were described as a major factor that explicitly influences food consumption in the U.S., while there was an implicit influence of external pressures through eating-related social interactions in France. In France, products considered "natural" where idealized and juxtaposed against processed and "industrial" products, whereas this was not a salient aspect in the U.S. (4) Conclusions: This first comparative qualitative study assessing aspects of food culture and eating behaviors across countries identifies both common and divergent attitudes to food and eating behavior. Further studies are needed to inform the development of effective behavioral interventions to address obesity in different populations.

Background: Dementia with Lewy bodies (DLB) and Parkinson disease dementia (PDD) are progressive and disabling neurodegenerative disorders, which are often misdiagnosed due to theirs overlapping clinical and paraclinical features. Nevertheless, their adequate management requires an accurate differential diagnosis. The main aim of this study was to investigate the usefulness of olfactory and trigeminal nasal testing for the differential diagnosis between DLB and PDD., Methods: Odor thresholds to three odorants differentially activating the olfactory and trigeminal systems were assessed in patients with DLB, PDD and healthy controls (n = 20 per group)., Results: Odor thresholds were significantly different between the three groups of subjects. More precisely, we found that DLB patients had significantly lower detection threshold performances compared to PDD patients. Moreover, using a standard canonical discriminant analysis, we confirmed a plain differentiation between the three groups., Conclusions: The current study highlights that DLB patients have very poor olfactory and trigeminal detection threshold performances, which are significantly lower, compared to PDD patients. These results suggest that olfactory testing, using odorants that stimulate both the olfactory and trigeminal systems, could constitute an interesting biomarker and contribute to the differential diagnosis of PDD and DLB patients. Further researches, notably on olfacto-trigeminal interactions, are warranted in these populations to support our findings.

To increase the knowledge about S. capitis in the neonatal setting, we conducted a nationwide 3-month survey in 38 neonatal intensive care units (NICUs) covering 56.6% of French NICU beds. We demonstrated 14.2% of S. capitis BSI (S.capBSI) among nosocomial BSIs. S.capBSI incidence rate was 0.59 per 1000 patient-days. A total of 55.0% of the S.capBSIs were late onset catheter-related BSIs. The S. capitis strains infected preterm babies (median gestational age 26 weeks, median birth weight 855 g). They were resistant to methicillin and aminoglycosides and belonged to the NRCS-A clone. Evolution was favorable in all but one case, following vancomycin treatment.

Recent anecdotal and scientific reports have provided evidence of a link between COVID-19 and chemosensory impairments, such as anosmia. However, these reports have downplayed or failed to distinguish potential effects on taste, ignored chemesthesis, and generally lacked quantitative measurements. Here, we report the development, implementation, and initial results of a multilingual, international questionnaire to assess self-reported quantity and quality of perception in 3 distinct chemosensory modalities (smell, taste, and chemesthesis) before and during COVID-19. In the first 11 days after questionnaire launch, 4039 participants (2913 women, 1118 men, and 8 others, aged 19-79) reported a COVID-19 diagnosis either via laboratory tests or clinical assessment. Importantly, smell, taste, and chemesthetic function were each significantly reduced compared to their status before the disease. Difference scores (maximum possible change ±100) revealed a mean reduction of smell (-79.7 ± 28.7, mean ± standard deviation), taste (-69.0 ± 32.6), and chemesthetic (-37.3 ± 36.2) function during COVID-19. Qualitative changes in olfactory ability (parosmia and phantosmia) were relatively rare and correlated with smell loss. Importantly, perceived nasal obstruction did not account for smell loss. Furthermore, chemosensory impairments were similar between participants in the laboratory test and clinical assessment groups. These results show that COVID-19-associated chemosensory impairment is not limited to smell but also affects taste and chemesthesis. The multimodal impact of COVID-19 and the lack of perceived nasal obstruction suggest that severe acute respiratory syndrome coronavirus strain 2 (SARS-CoV-2) infection may disrupt sensory-neural mechanisms., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Pancreatic cancer is a very aggressive cancer type associated with one of the poorest prognostics. Despite several clinical trials to combine different types of therapies, none of them resulted in significant improvements for patient survival. Pancreatic cancers demonstrate a very broad panel of resistance mechanisms due to their biological properties but also their ability to remodel the tumour microenvironment. Radiotherapy is one of the most widely used treatments against cancer but, up to now, its impact remains limited in the context of pancreatic cancer. The modern era of radiotherapy proposes new approaches with increasing conformation but also more efficient effects on tumours in the case of charged particles. In this review, we highlight the interest in using charged particles in the context of pancreatic cancer therapy and the impact of this alternative to counteract resistance mechanisms.

Olfaction is a sense involved in a complex set of tasks, influencing eating behavior, increasing awareness of environmental hazards and affecting social communication. Surprisingly, smell disorders are very frequent, especially in the elderly population. Several recent studies conducted mostly in older subjects have demonstrated a strong association between olfactory impairment and overall mortality risk, with anosmia being even more predictive of 5 years mortality risk than cardiovascular disease. Presently, the underlying pathophysiology linking olfactory impairment to mortality remains unknown and only putative mechanisms are suggested. This review aims to examine the link between olfactory impairment and mortality and to discuss existing ideas on underlying existing mechanisms including, (1) the effect of olfactory loss on nutrition, life-threatening situations and social interactions, (2) associated neurodegenerative diseases, (3) accelerated brain aging, and (4) reflection of general health status being reflected in olfactory function., (Copyright © 2020 Van Regemorter, Hummel, Rosenzweig, Mouraux, Rombaux and Huart.)

Tumor-associated macrophages (TAMs) represent potential targets for anticancer treatments as these cells play critical roles in tumor progression and frequently antagonize the response to treatments. TAMs are usually associated to an M2-like phenotype, characterized by anti-inflammatory and protumoral properties. This phenotype contrasts with the M1-like macrophages, which exhibits proinflammatory, phagocytic, and antitumoral functions. As macrophages hold a high plasticity, strategies to orchestrate the reprogramming of M2-like TAMs towards a M1 antitumor phenotype offer potential therapeutic benefits. One of the most used anticancer treatments is the conventional X-ray radiotherapy (RT), but this therapy failed to reprogram TAMs towards an M1 phenotype. While protontherapy is more and more used in clinic to circumvent the side effects of conventional RT, the effects of proton irradiation on macrophages have not been investigated yet. Here we showed that M1 macrophages (THP-1 cell line) were more resistant to proton irradiation than unpolarized (M0) and M2 macrophages, which correlated with differential DNA damage detection. Moreover, proton irradiation-induced macrophage reprogramming from M2 to a mixed M1/M2 phenotype. This reprogramming required the nuclear translocation of NFκB p65 subunit as the inhibition of IκBα phosphorylation completely reverted the macrophage re-education. Altogether, the results suggest that proton irradiation promotes NFκB-mediated macrophage polarization towards M1 and opens new perspectives for macrophage targeting with charged particle therapy.

The presence of cerebral lesions in patients with neurosensory alterations provides a unique window into brain function. Using a fuzzy logic based combination of morphological information about 27 olfactory-eloquent brain regions acquired with four different brain imaging techniques, patterns of brain damage were analyzed in 127 patients who displayed anosmia, i.e., complete loss of the sense of smell (n = 81), or other and mechanistically still incompletely understood olfactory dysfunctions including parosmia, i.e., distorted perceptions of olfactory stimuli (n = 50), or phantosmia, i.e., olfactory hallucinations (n = 22). A higher prevalence of parosmia, and as a tendency also phantosmia, was observed in subjects with medium overall brain damage. Further analysis showed a lower frequency of lesions in the right temporal lobe in patients with parosmia than in patients without parosmia. This negative direction of the differences was unique for parosmia. In anosmia, and also in phantosmia, lesions were more frequent in patients displaying the respective symptoms than in those without these dysfunctions. In anosmic patients, lesions in the right olfactory bulb region were much more frequent than in patients with preserved sense of smell, whereas a higher frequency of carriers of lesions in the left frontal lobe was observed for phantosmia. We conclude that anosmia, and phantosmia, are the result of lost function in relevant brain areas whereas parosmia is more complex, requiring damaged and intact brain regions at the same time.

Post-injury smell disorders., Problems/objectives: Head trauma is the third most common aetioiogy of post-traumatic olfactory loss (PTOL). This literature review aims to report the existing knowledge surrounding this issue, exploring the current understanding of the inducing pathogenesis and the assessment and management standards from the early phases to longer-term considerations., Methodology: Literature search and appraisal in PubMed on the following themes directly associated with PTOL: olfactory disorders, trauma, pathogenesis, examination, recovery and treatment., Results: Scientific evidence was mainly available for epidemiology and exploration tools in cases suffering from PTOL. The current research into obj6ctive batteries of olfactory tests is promising., Conclusions: This paper highlights the importance of an adequate assessment of PTOL for an early start in olfactory training.

Background: Olfactory dysfunction is deemed to be a significant contributor to poor quality of life in chronic rhinosinusitis (CRS)., Objective: To assess and to compare the effectiveness of three modalities of corticosteroids administration in patients with CRS., Study Design: A prospective randomized controlled study, Methods: Thirty patients with CRS were randomized in three groups depending on the route of corticosteroids administration: 16 days by oral route (Medrol (Pfizer, Belgique), 32 mg/8 days -16 mg/4 days-8 mg/4 days); nasal spray (Rhinocort (AstraZeneca, Belgique), 2 × 2 × 64 µg/nostril); or sonic nebulization (Pulmicort (AstraZeneca, Belgique), 2 × 1 mg/4 mL) (Sonic nebulizer, AOHBOX-NL11SN, DTF, France). Olfactory function was assessed using orthonasal threshold discrimination identification and retronasal psychophysical olfactory tests (RNT) before and after the treatment. Same intranasal modalities were previously tested for in vitro airways scintigraphic deposition., Results: In vitro differences in drug deposition pattern between both intranasal modalities were demonstrated. Threshold discrimination identification and RNT were similar between three groups at baseline. Threshold discrimination identification improved by 5.5, 5.8, and -1.1 for sonic nebulization, oral, and nasal spray groups, respectively (P = 0.010). This improvement was clinically relevant for oral and nebulized administration. It was similar between oral and nebulized administration but significantly higher than nasal spray administration. Retronasal psychophysical olfactory tests improved similarly for the three groups (P = 0.231) CONCLUSION: Effectiveness of sonic nebulized and oral administration is demonstrated on orthonasal olfactory. The clinical benefit is better than with nasal spray., (© 2014 The American Laryngological, Rhinological and Otological Society, Inc.)

Background: Amyloidosis is a rare pathology, due to a toxic accumulation of amyloid proteins infiltrating tissues. Published studies have low statistical power. However it seems that ENT localization have favorable prognosis. Management and check up are not well codified., Methods: Bicentric retros­pec­tive study conducted between 1987 and 2015, from patient diagnosed with ENT amyloidosis. The study was performed to the database of the pathology department. People concerned, history, symptoms and diagnostic features were analysed. The immunologic and clinical status, locations, extension check, treatment and prognosis have been evaluated., Results: Twenty patients were evaluated, ten men and ten women, average age was 55.5 year of age. Three patients were afflicted with familial amyloidosis. Main localisation was larynx (80%), main type was immunoglobulinic (AL) (80%). Amyloidosis was mostly localised (90%) and primary form (80%). Dysphonia was the most frequently encountered symptom. Most performed exami­na­tion were local biopsy and creatinine clearance (100%), serum protein electrophoresis (SEP) (89%), myelogram and/or bone marrow aspiration (75%), and trans thoracic echography (TTE) (75%). Surgical removal was performed for 75% of the patients. Global rate of recurrence was 70%, about 4.6 years after diagnosis. In familial forms, overall survival was 66% at ten years. In non-familial forms, overall survival was 100%., Conclusion: ENT amyloidosis are mostly AL, laryngeal, prima­ry and localised. Distant extension check should be managed by internal medicine specialist and associate creati­ni­ne clea­ran­ce, local biopsy, TTE, SEP and myelogram. Head and neck forms treatment is based on surgical removal, familial forms are of poor prognosis.

The aim of this study was to investigate the olfactory bulb (OB) and sulcus (OS) in a large group of patients who have been well-characterized in terms of olfactory function, with a specific focus on the comparison between patients with olfactory loss due to chronic rhinosinusitis, head trauma, or acute infections. A retrospective study of 378 patients with olfactory loss was performed. Orthonasal olfactory function was assessed with the"Sniffin' Sticks" test kit, including tests for odor threshold, odor discrimination, and odor identification. Magnetic resonance imaging analyses were focused on OB volume and OS depth. Major results of the present study included the (1) demonstration of a correlation between olfactory function and OB volume across the various pathologies in a very large group of subjects; (2) the three functional tests exhibited a similar degree of correlation with OB volume. (3) The right, but not the left OS correlated with olfactory function; in addition, (4) OS was negatively correlated with age. In contrast to OS, (5) no side differences were found for the OB. Finally, (6) the three different causes of olfactory loss exhibited different patterns of results for the three olfactory tests. The present data suggest that the morphological assessment of the OB volume and OS depth produces useful clinical indicators of olfactory dysfunction.

Background: Olfactory dysfunction is associated with Alzheimer's disease (AD), and already present at pre-dementia stage., Objectives: Based on the assumption that early neurodegeneration in AD is asymmetrical and that olfactory input is primarily processed in the ipsilateral hemisphere, we assessed whether unirhinal psychophysical and electrophysiological assessment of olfactory function can contribute to the diagnostic workup of mild cognitive impairment (MCI)., Methods: Olfactory function of 13 MCI patients with positive amyloid PET, 13 aged-matched controls (AC) with negative amyloid PET and 13 patients with post-infectious olfactory loss (OD) was assessed unirhinally using (1) psychophysical testing of olfactory detection, discrimination and identification performance and (2) the recording of olfactory event-related brain potentials. Time-frequency analysis was used to enhance the signal-to-noise ratio of the electrophysiological responses. Psychophysical and electrophysiological assessment of auditory and trigeminal chemosensory function served as controls., Results: As compared to AC and OD, MCI patients exhibited a significant asymmetry of olfactory performance. This asymmetry efficiently discriminated between MCI and AC (sensitivity: 85% , specificity: 77% ), as well as MCI and OD (sensitivity: 85% , specificity: 70% ). There was also an asymmetry of the electrophysiological responses, but not specific for MCI. In both MCI and OD, olfactory stimulation of the best nostril elicited significantly more activity than stimulation of the worse nostril, between 3-7.5 Hz and 1.2-2.0 s after stimulus onset. Trigeminal and auditory psychophysical testing did not show any difference between groups., Conclusion: MCI patients exhibit a marked asymmetry of behavioral olfactory function, which could be useful for the diagnostic workup of MCI.

Objectives: To evaluate olfactory event-related potentials (OERPs) as an objective measurement of olfactory function in infants., Study Design: OERPs to phenylethyl alcohol were measured in 13 infants, between 23 and 41 days of age. The odor was delivered with a computer-controlled olfactometer. Recording electrodes were applied using the 10-20 system. Data from electrodes Fz, Cz, Pz, C3, and C4 were analyzed by MatLab's Letswave toolbox (André Mouraux, Brussels, Belgium) using the canonical time-domain averaging as well as the time-frequency analyzing method., Results: Ten of 13 infants finished the recording session. We observed OERPs in 7 of these 10 infants. Recordings were best in electrodes Fz and Cz. The N1 peak was visible at 328 ms followed by P2 at 505 ms. In addition, the time-frequency analysis had an increase in low frequencies (4-7 Hz) around 550 ms after odor presentation., Conclusions: We were able to record OERPs in infants. The time-domain averaging as well as the time-frequency analysis was of value for data analysis., (Copyright © 2014 Elsevier Inc. All rights reserved.)

In the last years, an increasing interest has been paid to the olfactory system, particularly to its abilities of plasticity and its potential continuous neurogenesis throughout adult life. Although mechanisms underlying adult neurogenesis have been largely investigated in animals, to some degree they remain unclear in humans. Based on human research findings, the present review will focus on the olfactory bulb as an evidence of the astonishing plasticity of the human olfactory system.

Objectives: Several prognostic factors influencing the recovery from olfactory dysfunction have been described. The aim of this study was to investigate whether olfactory bulb volume could be used as a new predictor of olfactory recovery in postinfectious and posttraumatic olfactory loss., Study Design: Cohort study; Level of evidence, 4. Setting Tertiary university clinic, department of otolaryngology., Subjects and Methods: A cohort of 60 patients with postinfectious (n = 28) and posttraumatic olfactory loss (n = 32) was investigated. Assessment of olfactory function was performed using orthonasal (Sniffin' Sticks test) and retronasal psychophysical olfactory tests, at the time of the diagnosis (t1) and 15 months later (t2). All patients were examined on 3 tesla magnetic resonance imaging, and the olfactory bulbs volume was assessed using planimetric contouring at the time of the diagnosis (t1)., Results: Recovery rate was 25% in patients with posttraumatic olfactory loss and 36% in patients with postinfectious olfactory loss. There was a correlation between both orthonasal and retronasal olfactory testing and the initial measurement of the total olfactory bulb volume. In addition, we observed a significant correlation between changes in olfactory functions and initial measurement of the total olfactory bulb volume, with larger volumes relating to higher improvement of olfactory function. Finally, we found that none of the patients with a total olfactory bulb volume of 40 mm(3) or less exhibited recovery of olfactory function., Conclusion: Olfactory bulb volume seems to be a predictor of olfactory recovery in patients with postinfectious and posttraumatic olfactory loss.

Background: The recording of olfactory and trigeminal chemosensory event-related potentials (ERPs) has been proposed as an objective and non-invasive technique to study the cortical processing of odors in humans. Until now, the responses have been characterized mainly using across-trial averaging in the time domain. Unfortunately, chemosensory ERPs, in particular, olfactory ERPs, exhibit a relatively low signal-to-noise ratio. Hence, although the technique is increasingly used in basic research as well as in clinical practice to evaluate people suffering from olfactory disorders, its current clinical relevance remains very limited. Here, we used a time-frequency analysis based on the wavelet transform to reveal EEG responses that are not strictly phase-locked to onset of the chemosensory stimulus. We hypothesized that this approach would significantly enhance the signal-to-noise ratio of the EEG responses to chemosensory stimulation because, as compared to conventional time-domain averaging, (1) it is less sensitive to temporal jitter and (2) it can reveal non phase-locked EEG responses such as event-related synchronization and desynchronization., Methodology/principal Findings: EEG responses to selective trigeminal and olfactory stimulation were recorded in 11 normosmic subjects. A Morlet wavelet was used to characterize the elicited responses in the time-frequency domain. We found that this approach markedly improved the signal-to-noise ratio of the obtained EEG responses, in particular, following olfactory stimulation. Furthermore, the approach allowed characterizing non phase-locked components that could not be identified using conventional time-domain averaging., Conclusion/significance: By providing a more robust and complete view of how odors are represented in the human brain, our approach could constitute the basis for a robust tool to study olfaction, both for basic research and clinicians.

This paper reviews the contribution of the different parts of the oral cavity and the pharynx to the basic physiology of breathing, phonation, speech, swallowing, and of Waldeyer's ring to the functioning of the immune system. We discuss the development of taste and smell, as well as possibilities for chemosensory testing in children.

Adenotonsillar hypertrophy is a common paediatric/otolaryngological disorder that may be associated with secondary growth or facial growth impairment, sleep disturbances, neurocognitive deficits, or smell loss. Surgical removal of the hypertrophic tissue eliminates the mechanical obstacle of the airways and is therefore curative in most cases. The purpose of the present review is to outline the impact of adenotonsillar hypertrophy and adenotonsillectomy on growth, facial growth, sleep, behaviour and smell.

Background and Purpose: In congenital anosmia, the OB and OT can be aplastic or hypoplastic. In clinical routine, these are sometimes difficult to assess. We thus wanted to investigate morphologic differences of the OS in patients with IA since birth or early childhood in comparison with controls, to investigate whether there is a depth of OS that is predictive of IA., Materials and Methods: Within the context of a 2-center study, we investigated 36 patients with IA in comparison with 70 controls. MR imaging was performed with a standard quadrature head coil (1.5T; T1- and T2-weighted spin-echo sequences were used on the coronal plane). We assessed the depth of OS in the PPTE., Results: Looking at the depth of the OS in the PPTE, we found that patients with IA had a significantly smaller OS compared with controls (P < .001). None of the healthy controls exhibited a depth of <8 mm. In patients with IA, 10 had an OS deeper than 8 mm, while 26 had an OS smaller than 8 mm. Thus, a depth of the OS less than 8 mm clearly indicates IA, with a specificity of 1 and a sensitivity of 0.72., Conclusions: In IA, the depth of the OS in the PPTE is a useful clinical indicator. Indeed, if it is ≤8 mm, it clearly indicates IA, with a specificity of 1.

This report describes cartilaginous regeneration in a cricoarytenoid joint affected by spondyloarthropathy using tumor necrosis factor-alpha (TNF-α) blockade, monitored by magnetic resonance (MR) and computed tomography (CT) imaging. This case is interesting for several reasons. It is only the eighth case of destructive ankylosing spondylitis-related cricoarytenoid arthritis published in the English language literature. It describes, for the first time, full recovery of vocal cord mobility following TNF-α blockade. It is also the first case to be published with MR imaging demonstrating regeneration of the cricoarytenoid cartilage following treatment. This case represents a landmark in the treatment of patients presenting with destructive arthritis involving the cricoarytenoid joint., (Copyright © 2011 The American Laryngological, Rhinological, and Otological Society, Inc.)

It has been shown that the volume of the olfactory bulb (OB) changes with function. The aim of this study was to investigate whether the OB volume and the olfactory function in early blind (EB) subjects increase compared with controls. Psychophysical testing of olfactory performances and OB volumetric measurements assessed by an MRI scan were studied. Quantitative olfactory function expressed in the odor discrimination and odor-free identification scores was higher in EB subjects compared with controls. The mean of right, left and total OB volume was 65.40, 75.48, and 140.89 mm, respectively for the EB subjects and 54.47, 52.11, and 106.60 mm, respectively for the controls, with these differences being significant. EB subjects have superior olfactory abilities and presented with significantly higher OB volume than the sighted controls. OB plasticity may explain this compensatory mechanism between visual deprivation and enhanced olfactory perception.