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An anomalous winter phytoplankton bloom was observed across the central Gulf of Maine during a winter cruise in late February 1999, but not during a similar mission to the same region in late February 2000. During the cruise in 1999, 0 to 40 m mean chl a concentrations were >2 μg 1-1, while in 2000 total chl a concentrations were 5 pm size fractions were 10x more abundant in 1999 and included species typically not present in the central Gulf during winter. All developmental stages of planktonic copepods were present, including large numbers of older copepodid stages of species such as Calanus finmarchicus, indicating that the bloom had been proceeding for some time. RNA:DNA ratios of surface C. finmarchicus stage C5 and adult females were at or near maximum temperature-dependent values in 1999, but were considerably reduced in 2000. Egg production rates of C. finmarchicus were high in 1999 but reduced in 2000. Both showed a curvilinear relationship with chl a. Analysis of gonads of females of other copepod species indicate similar between-year differences in reproductive rates. We suggest that the presence of the winter bloom in the central Gulf of Maine allows an extra generation of C. finmarchicus and other copepods to develop, leading to a buildup of the population during winter. This will have significant effects on downstream regions such as Georges Bank, which depend on re-supply from the Gulf of Maine.

Objective: To assess the effect of allergen immunotherapy (AIT) on patients with central compartment atopic disease (CCAD) and house dust mite (HDM) sensitization post-surgery., Methods: A retrospective cohort of surgically treated, HDM-sensitized CRSwNP patients phenotyped as CCAD was assessed. Patients were divided into two groups based on whether they had AIT commenced as part of their surgical care. All AIT patients started immunotherapy prior to their surgery. The primary endpoint was reformation of middle turbinate (MT) edema 12 months postsurgery. Secondary endpoints were corticosteroid irrigation use (<4 times/week vs. ≥4 times/week, %) and the rhinologic domain of the 22-item sino-nasal outcome test (SNOT-22). Demographic characteristics, concomitant asthma, smoking status, history of aspirin-exacerbated respiratory disease, conjunctival symptoms, polysensitization, serum eosinophils (cell × 10 9 /L), tissue eosinophilia (% > 100/HPF), and serum IgE (kU/L) were also recorded., Results: Eighty-six CCAD patients were assessed (41 ± 14 yrs, 64% female). AIT was applied in 37% (n = 32). Baseline features were similar apart from greater conjunctival symptoms (72 vs. 45%, p = 0.02) in the AIT group. At 12 months post-surgery, the AIT group has less MT edema (% ≥ diffuse 15.6 vs. 52.9, p < 0.01). Patients on AIT also had less pharmacotherapy requirements at 12 months (% ≥ 4/week, 37.5 vs. 79.6%, p < 0.01). The rhinologic symptoms were similar (21.1 ± 17.1 vs. 20.1 ± 21.6, p = 0.83)., Conclusions: Surgery and pharmacotherapy are effective in managing CCAD, but the addition of AIT improved allergic phenomenon and allowed de-escalation of topical therapy. Longer term studies are required to demonstrate further immunomodulation., (© 2024 The Author(s). International Forum of Allergy & Rhinology published by Wiley Periodicals LLC on behalf of American Academy of Otolaryngic Allergy and American Rhinologic Society.)

Objective: Nasal airway surgery is often applied when treatment fails to relieve nasal obstruction. However, surgery that improves airflow does not always alleviate the symptoms of nasal obstruction. The perception of nasal breathing is likely more related to changes in mucosal temperature than the mechanical sensation of flow or pressure. This study aims to measure intranasal mucosal temperature pre-and post-surgery using endonasal thermal imaging, exploring its correlation with subjective nasal breathing and objective airflow measurements., Methods: A prospective study of adult patients with nasal obstruction managed with nasal airway surgery was performed. Intranasal mucosal temperatures were determined using the thermal endonasal image of the nasal passage produced by the infrared radiometric thermal camera (FILR VS290). A comparison was made between the mean values of mid-expiration (ExT) and mid-inspiration (InT) temperature data (internal nasal valve, nasal cavity, inferior turbinate, and overall airway [mean value]) and visual analog scale (VAS), Nasal Obstruction Symptom Evaluation (NOSE) scale and nasal airway resistance (NAR) before and after surgery., Results: Seven patients (35.14 ± 16.45 years, 57.14% female) were included. All NOSE, VAS, and NAR improved after surgery (59.29 ± 10.89 vs 17.14 ± 14.64; P  < .001, 64.50 ± 26.79 vs 18.57 ± 19.99; P  < .001, 0.82 ± 0.48 vs 0.34 ± 0.11 Pa/cm 3 /s; P  = .002, respectively). ExT, InT, and the difference between ExT and InT of three areas and overall airway were similar between pre-and post-surgery. No statistically significant correlations were found between intranasal mucosal temperature, VAS, NOSE, and NAR at pre-and post-surgery except for the difference between ExT and InT of overall airway and NOSE pre-operative (Pearson r  = 0.57; 95% CI 0.06-1.09; P  = .03)., Conclusion: Endonasal thermal imaging can assess the intranasal mucosal temperature of a patient. However, more precise imaging of the nasal passages and data acquisition are required to establish mucosal temperature as an objective measure of nasal obstruction before and after nasal airway surgery in a clinical setting., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: RJ Harvey is consultant/advisory board with Medtronic, Novartis, Glaxo-Smith-Kline and Meda pharmaceuticals. He has received research grants from GSK, Sanofi, and Stallergenes. He has been on the speakers’ bureau for Glaxo-Smith-Kline, Astra-zeneca, Meda Pharmaceuticals and Seqirus. L Kalish is on the speakers’ bureau for Mylan, and Seqirus Pharmaceuticals. J Rimmer has honoraria with Sanofi Aventis, Novartis, Mundipharma, GSK, and Stallergenes. RG Campbell is on the speakers’ burea for Medtronic, Seqirus, GSK and Viatris. K Snidvongs received honoraria for speaking at symposia from Organon, Viatris, and Menarini. R Sacks is a consultant for Medtronic and is on the speakers bureau for Meda Pharmaceuticals. All other authors have no personal, financial, or institutional interest in any drugs, materials, or devices described in this article.

Objectives: The aim was to assess the developmental attributes of sphenoid sinuses affected by fungal balls and describe a surgical approach which reestablishes gravity-dependent drainage to compensate for any mucociliary dysfunction., Methods: A within-patient case-control analysis was performed on sphenoid sinus dimensions from patients with sphenoid sinus fungal ball (SSFB). Radiological dimensions were assessed to determine the dominant or larger sinus by volume and width. Pneumatization in the sagittal and lateral extent was assessed. The influence of sinus size and pneumatization variants within a patient was analyzed. Patency and the presence of mucostasis from radical reshaping of the sinus cavity were documented at least 3 months after surgery. Complications (bleeding, cerebrospinal fluid leak, and cranial nerve palsy) were recorded., Results: Twenty-three patients (59 ± 19 years, 86% female, 46 sphenoid sinuses) were assessed. Fungal ball was more common in the smaller (non-dominant) sinus, by width (78% vs. 22%, p < 0.01) and by proportion of total sphenoid volume (0.39 ± 0.16 vs. 0.61 ± 0.16, p < 0.01). Pneumatization variants did not influence the development of SSFB within a patient. All patients had patency and the absence of mucostasis or persistent inflammation at last follow-up. No complications were reported., Conclusion: The smaller or nondominant sphenoid sinus is more affected by SSFB. Surgical reshaping of the sphenoid to prevent mucostasis is favorable in managing the smaller affected sinus cavity., Level of Evidence: 4 Laryngoscope, 134:4888-4892, 2024., (© 2024 The American Laryngological, Rhinological and Otological Society, Inc.)

The lateral recess of a well-pneumatized sphenoid sinus is challenging to access surgically. Traditional methods require the use of multiple angled endoscopes and curved instruments which may limit visualization. We describe a prelacrimal-transpterygoid/maxillary approach which offers direct access to this region with a 0° endoscope. Laryngoscope, 134:4918-4922, 2024., (© 2024 The American Laryngological, Rhinological and Otological Society, Inc.)

Background: With the recent proliferation of novel therapeutics for chronic rhinosinusitis with nasal polyps (CRSwNP), there is an immediate need for comprehensive means to assess CRSwNP disease status as well as to determine treatment efficacy. Outcome measures exist in different forms. Patient-reported outcome measures (PROMs) allow patients to provide direct input about their condition that is not possible to obtain in any other way. Common constructs that are measured using PROMs include quality of life or the burden of disease manifestations (e.g., symptom severity). Outcomes may also include the results of objective diagnostic testing/measurement of clinical signs or measured using psychophysical tests. Biomarkers represent an emerging class of outcome measures for CRSwNP and are chosen to directly reflect the active pathophysiologic processes of CRSwNP in the peripheral blood, sinus/polyp tissues, and sinonasal mucus., Methods: Narrative review of the literature, identifying and describing outcome measures that may be used in the evaluation of CRSwNP and for assessment of treatment responses., Results: In this review, we identify many different outcome measures for CRSwNP that fall under the categories of PROM, objective test, psychophysical test or biomarker. We describe the history of each - including seminal studies - and demonstrate the formal validation, psychometric performance, and limitations of each., Conclusions: PROMs, objective tests, psychophysical tests and biomarkers represent different classes of outcome measures that are complementary means of assessing CRSwNP disease status and treatment efficacy. The choice or interpretation of a CRSwNP outcome measure should be undertaken with full knowledge of its formal validation, psychometric performance, and limitations.

Objective: Endoscopic sinus and skull base surgery has led to significant improvements in patient outcomes, yet may have come at a cost to surgeons' musculoskeletal (MSK) health. We aimed to determine the prevalence and characteristics of work-related MSK disorders (WRMDs) in endoscopic sinus and skull base surgeons; to investigate contributing factors for WRMD in this population; and to evaluate the effectiveness of ergonomic interventions on the severity or prevalence of WRMD in this population., Data Sources: Medline, Embase, CINAHL, Web of Science, and Scopus from inception to April 2, 2024. A bibliographic examination was performed for further papers., Review Methods: Inclusion criteria included original peer-reviewed papers with work-related MSK outcomes (prevalence, contributing factors, and interventions) relating to endoscopic sinus and/or skull base surgeons in any language., Results: Of 25,772 unique citations, 37 studies met the inclusion criteria. The pooled lifetime, point, and 12-month prevalences of WRMD were 75.9% (95% confidence interval; I 2 , 67.2%-83.6%, I 2 95.6%), 80.8% (77.0%-84.3%, I 2 98.0%), and 82.0% (71.8%-90.3%, I 2 60.96%) respectively. The neck, lumbar spine, and thoracic spine were the most commonly involved areas. One of 9 studies on contributing factors investigated discomfort as an outcome. The remainder focussed on surrogate outcomes (eg, posture, hand dysfunction). Two of the 13 intervention studies investigated pain or fatigue as an outcome. The remainder targeted posture, muscle activity, or workload., Conclusion: WRMDs are highly prevalent in endoscopic sinus and skull base surgeons. Further studies focusing on the direct outcomes of WRMD such as pain are needed., (© 2024 The Author(s). Otolaryngology–Head and Neck Surgery published by Wiley Periodicals LLC on behalf of American Academy of Otolaryngology–Head and Neck Surgery Foundation.)

2-Arylethynyl (N)-methanocarba adenosine 5'-methylamides are selective A 3 adenosine receptor (AR) agonists containing a preestablished receptor-preferred pseudoribose conformation. Here, we compare analogues having bulky 2-substitution, either containing or lacking an ethynyl spacer between adenine and a cyclic group. 2-Aryl compounds 9 - 11 , 13 , 14 , 19 , 22 , 23 , 27 , 29 , 31 , and 34 , lacking a spacer, had human (h) A 3 AR K i values of 2-30 nM, and others displayed lower affinity. Mouse (m) A 3 AR affinity varied, with 2-arylethynyl having a higher affinity than 2-aryl analogues ( 7 , 8 > 3c , 3d > 3b ). However, 2-aryl-4'-truncated derivatives had greatly reduced hA 3 AR affinity, even containing affinity-enhancing N 6 -dopamine-derived substituents. Molecular modeling, including molecular dynamics simulation, predicted stable poses in the canonical A 3 AR agonist binding site, but 2-aryl (ECL2 interactions) and 2-arylethynyl (TM2 interactions) substituents have different conformations and environments. In a hA 3 AR miniGα i recruitment assay, 31 (MRS8062) was (slightly) more potent compared to a β-arrestin2 recruitment assay, both in engineered HEK293T cells, and its maximal efficacy ( E max ) was much higher (165%) than reference agonist NECA's. Thus, in the 2-aryl series, A 3 AR affinity and selectivity were variable and generally reduced compared to the 2-arylethynyl series, with a greater dependence on the specific aryl group present. Selected compounds were studied in vivo in an ischemic model of peripheral artery disease (PAD). Rigidified 2-arylethynyl analogues 3a - 3c were protective in this model of skeletal muscle ischemia-reperfusion injury/claudication, as previously shown only for moderately A 3 AR-selective ribosides or (N)-methanocarba derivatives. Thus, we have expanded the A 3 AR agonist SAR for (N)-methanocarba adenosines., Competing Interests: The authors declare no competing financial interest., (© 2024 American Chemical Society.)

Background: Nasal obstruction, triggered by allergic rhinitis, often does not resolve with allergen-specific immunotherapy (AIT) alone, thus inferior turbinate reduction surgery (ITR) may be required. This study aims to investigate the impact of combined treatment on nasal obstruction, as evidence is currently limited., Methodology/principal: A retrospective cohort study of perennial allergic rhinitis patients experiencing nasal obstruction and undergoing ≥12 months AIT was conducted. Two groups were derived, those undergoing AIT-with or without an ITR. Patient reported nasal obstruction (evaluated with questionnaires) and nasal airway function (Nasal Peak Inspiratory Flow [NPIF] and Nasal Airflow Resistance [NAR]) were monitored. The change from baseline to 12 months post-treatment in each group were compared., Results: A total of 118 patients (33.71 ± 14.43 years, 41.5% female) were recruited, 72% had AIT and 28% AIT&ITR. At baseline, the AIT&ITR group had a higher level of nasal obstruction (>moderate%; 63.6% vs 52.9%, P  = .048). Post treatment, AIT&ITR group reported greater reduction in nasal obstruction (>1 category change: 75.8% vs 48.2%, P  = .002). Similarly, the AIT&ITR group had greater improvement in nasal function by NPIF (-13.9 ± 110.3 L/minute vs -3.4 ± 78.1 L/minute, P  = .049) and NAR (-0.120 ± 0.342 Pa/cm³/second vs -0.093 ± 0.224 Pa/cm³/second, P  = .050)., Conclusions: Allergic rhinitis patients, with moderate to severe nasal obstruction, who undergo combined AIT&ITR have greater relief of nasal obstruction and improved airflow analysis compared to AIT alone., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Richard J Harvey is a consultant/advisory board with Medtronic, Novartis, GSK and Meda pharmaceuticals and received research grant funding from Glaxo-Smith-Kline. He has been on the speakers’ bureau for Glaxo-Smith-Kline, Astra-zeneca, Meda Pharmaceuticals, and Seqirus. Both Richard J Harvey and Raquel Alvarado have affiliations to the School of Clinical Medicine, St Vincent’s Healthcare Clinical Campus, Faculty of Medicine and Health, UNSW Sydney, Australia. Janet Rimmer has honoraria with Sanofi Aventis, Novartis, Mundipharma, BioCSL, Stallergenes. Raewyn Campbell has honoraria with Medtronic, Seqirus, Viatris, and Novartis steering committee. Larry Kalish is on the speakers’ bureau for Care Pharmaceuticals, Mylan, and Seqirus Pharmaceuticals.

Background: Biologic therapy targeting type 2 chronic rhinosinusitis with nasal polyps (CRSwNP) has greatly improved disease control but nonresponders exist in a proportion of patients in phase 3 trials and clinical practice. This study explores the serum and histologic changes in biologic treated CRSwNP that predict disease control., Methods: A cross-sectional study was performed of patients with CRSwNP on biologics for their asthma, who underwent endoscopic sinus surgery while on biologic therapy. At the 6-month postoperative assessment, patients with poorly controlled CRSwNP while on biologic therapy were compared to patients who were controlled. Blood and mucosal samples taken at the time of surgery 6 months prior were assessed to predict disease control., Results: A total of 37 patients were included (age 47.8 ± 12.4 years, 43.2% female). Those with poorly controlled disease had reduced tissue eosinophils (% >100 cells/high-powered field: 8.3% vs. 50.0%, p < 0.001) and increased serum neutrophils (5.2 ± 2.7 vs. 3.7 ± 1.1 × 10 9 cells/L, p = 0.02). Logistic regression analysis demonstrated that reduced tissue eosinophil was predictive for poorly controlled disease (OR = 0.21, 95% CI [0.05, 0.83], p = 0.03). Receiver-operating characteristic analysis showed that need for rescue systemic corticosteroid was predicted at a serum neutrophil cut-off level of 5.75 × 10 9 cells/L (sensitivity = 80.0%, specificity = 96.9%, AUC = 0.938, p = 0.002)., Conclusion: Low tissue eosinophils and increased serum neutrophils while on biologics predict for poor response in the biological treatment of with CRSwNP. A serum neutrophil level of ≥5.75 × 10 9 cells/L predicts for poor response to current biologic therapy., (© 2023 The Authors. International Forum of Allergy & Rhinology published by Wiley Periodicals LLC on behalf of American Academy of Otolaryngic Allergy and American Rhinologic Society.)

Surgeons have a high rate of work-related musculoskeletal injuries; an area that has received little attention. These injuries result in surgeons performing less efficiently, needing to take time off work, suffering higher rates of burnout, and may ultimately lead surgeons to retire earlier than planned. Otorhinolaryngologists are at particular risk for work-related musculoskeletal injuries. Beyond the clinician, sustaining such injuries can negatively impact patient safety. Ergonomic interventions have been used effectively to reduce work-related musculoskeletal injuries in other professions, yet not in surgery. With traditional teachings of ideal body postures to avoid injury and manual handling training being re-evaluated, it is important to explore evidence based interventions for reducing work-related musculoskeletal injuries in otorhinolaryngologists. New research encourages us to shift the focus away from the traditional one-size-fits-all approach to ergonomics and toward postural recommendations and education that promote a dynamic, individualized approach to avoiding sustained, static and awkward postures., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Purpose of Review: The upper and lower airways are inter-related despite serving different functions and can no longer be considered separately. Rhinologists are becoming increasingly aware of the role the lower airway plays in optimizing outcomes for their patients. This review highlights recent developments in pulmonology that impact rhinologic conditions., Recent Findings: The unified airway concept now supports the multidisciplinary management of respiratory and rhinologic pathologies. Biomarkers, biologics and the concept of treatable traits have permitted the development of personalized and precise treatment of the entire respiratory tract. The concept of corticosteroid stewardship, the introduction of steroid sparing agents for the treatment of respiratory diseases and the development of biomarkers, now forces us to be more considerate and precise with oral corticosteroid (OCS) prescribing and to consider reduction regimens. Finally, current research on climate change and vaping will allow us to better educate and prepare our patients to improve adherence and avoid exacerbations to maintain optimal global respiratory health., Summary: The inter-relatedness of the upper and lower airway has encouraged a multidisciplinary focus in respiratory medicine. More research is required to improve the precision respiratory medicine model, particularly in the realm of biomarkers and endotyping. These developments must also consider the impact of climate change, pollution and toxins for us to provide optimum care for our patients., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Microalgae are the main source of the omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), essential for the healthy development of most marine and terrestrial fauna including humans. Inverse correlations of algal EPA and DHA proportions (% of total fatty acids) with temperature have led to suggestions of a warming-induced decline in the global production of these biomolecules and an enhanced importance of high latitude organisms for their provision. The cold Arctic Ocean is a potential hotspot of EPA and DHA production, but consequences of global warming are unknown. Here, we combine a full-seasonal EPA and DHA dataset from the Central Arctic Ocean (CAO), with results from 13 previous field studies and 32 cultured algal strains to examine five potential climate change effects; ice algae loss, community shifts, increase in light, nutrients, and temperature. The algal EPA and DHA proportions were lower in the ice-covered CAO than in warmer peripheral shelf seas, which indicates that the paradigm of an inverse correlation of EPA and DHA proportions with temperature may not hold in the Arctic. We found no systematic differences in the summed EPA and DHA proportions of sea ice versus pelagic algae, and in diatoms versus non-diatoms. Overall, the algal EPA and DHA proportions varied up to four-fold seasonally and 10-fold regionally, pointing to strong light and nutrient limitations in the CAO. Where these limitations ease in a warming Arctic, EPA and DHA proportions are likely to increase alongside increasing primary production, with nutritional benefits for a non-ice-associated food web., (© 2023 The Authors. Global Change Biology published by John Wiley & Sons Ltd.)

Purpose: Microscopic Draf 2a frontal sinusotomy relied on direct access. However, the modern-day endoscopic approach is hindered by the anterior-posterior dimensions of the frontal recess. The nasofrontal beak, angled endoscopes, and variable frontal recess anatomy make the surgery challenging. Carolyn's window frontal sinusotomy removes the limitation of anterior-posterior dimensions and is an endoscopic version of the microscopic Draf 2a. This study aims to compare the perioperative outcomes and morbidity from endoscopic direct access Draf 2a compared to angled access Draf 2a., Methods: Consecutive adult patients (> 18 years) seen at a tertiary referral clinic who underwent Draf 2a frontal sinus surgery using either endoscopic direct access (Carolyn's window) or endoscopic angled instrumentation were included. Patients who underwent Carolyn's window were compared to those with angled Draf 2a frontal sinusotomy., Results: One hundred patients (age 51.96 ± 15.85 years, 48.0% female, follow-up 60.75 ± 17.34 months) were included. 44% of patients used Carolyn's window approach. 100% [95% CI 98.2-100%] of patients achieved successful frontal sinus patency. Both groups were comparable for early morbidities (bleeding, pain, crusting, and adhesions) and late morbidities (retained frontal recess partitions). There were no other morbidities in the early and late postoperative periods., Conclusion: The endoscopic direct access Draf 2a, or Carolyn's window, removes the anteroposterior diameter limitation. The frontal sinus patency and early and late surgical morbidities of direct access Draf 2a were comparable with the angled Draf 2a frontal sinusotomy. Surgical modifications, often with drills and bone removal, can be successfully made to enhance access in endoscopic sinus surgery without concern for additional morbidity., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Competing Interests: The authors report no conflicts of interest.

(N)-Methanocarba adenosine derivatives were structurally modified to target 5-HT 2B serotonin receptors as antagonists, predominantly containing branched N 6 -alkyl groups. N 6 -Dicycloalkyl-methyl groups, including their asymmetric variations, as well as 2-iodo, were found to generally favor 5-HT 2 Rs, while only N 6 -dicyclohexyl-methyl derivative 35 showed weak 5-HT 2A R affinity (K i 3.6 μM). The highest 5-HT 2B R affinities were K i 11-23 nM (N 6 -dicyclopropyl-methyl-2-iodo 11, 2-chloro-5'-deoxy-5'-methylthio 15 and N 6 -((R)-cyclobuty-cyclopropyl-methyl)-2-iodo 43), and K i 73 nM at 5-HT 2C R for 36. Direct comparison of adenine ribosides and their corresponding rigid (N)-methanocarba derivatives (cf. 51 and MRS8099 45) indicated a multifold affinity enhancement with the bicyclic ring system. Compounds 43, 45 and 48 were functional 5-HT 2B R (K B 2-3 nM) and 5-HT 2C R (K B 79-328 nM) antagonists in a G q -mediated calcium flux assay, with 5-HT 2B R functional selectivity ranging from 45- (48) to 113-fold (43). Substantial adenosine receptor (AR) affinity (K i , A 1 AR < K i , A 3 AR < K i , A 2A AR) was still present in this series, suggestive of dual acting compounds: 5-HT 2B antagonist and A 1 AR agonist, potentially useful for treating chronic conditions (fibrosis; pain). Given its affinity (17 nM) and moderate 5-HT 2B R binding selectivity (32-fold vs. 5-HT 2C R, 4-fold vs. A 1 AR), 43 (MRS7925) could potentially be useful for anti-fibrotic therapy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier Masson SAS.)

Background: The Cavernous Hemangioma Exclusively Endonasal Resection (CHEER) staging system has become the gold standard for outcomes reporting in endoscopic orbital surgery for orbital cavernous hemangiomas (OCHs). A recent systematic review demonstrated similar outcomes between OCHs and other primary benign orbital tumors (PBOTs). Therefore, we hypothesized that a simplified and more comprehensive classification system could be developed to predict surgical outcomes of other PBOTs., Methods: Patient and tumor characteristics as well as surgical outcomes from 11 international centers were recorded. All tumors were retrospectively assigned an Orbital Resection by Intranasal Technique (ORBIT) class and stratified based on surgical approach as either exclusively endoscopic or combined (endoscopic and open). Outcomes based on approach were compared using chi-squared or Fisher's exact tests. The Cochrane-Armitage test for trend was used to analyze outcomes by class., Results: Findings from 110 PBOTs from 110 patients (age 49.0 ± 15.0 years, 51.9% female) were included in the analysis. Higher ORBIT class was associated with a lower likelihood of gross total resection (GTR). GTR was more likely to be achieved when an exclusively endoscopic approach was utilized (p < 0.05). Tumors resected using a combined approach tended to be larger, to present with diplopia, and to have an immediate postoperative cranial nerve palsy (p < 0.05)., Conclusion: Endoscopic treatment of PBOTs is an effective approach, with favorable short-term and long-term postoperative outcomes as well as low rate of adverse events. The ORBIT classification system is an anatomic-based framework that effectively facilitates high-quality outcomes reporting for all PBOTs., (© 2023 ARS-AAOA, LLC.)

Background: Middle meatal antrostomy (MMA) is the traditional intervention for chronic maxillary sinusitis but often fails to correct a nonfunctioning maxillary sinus that has lost its capability for mucociliary clearance. Endoscopic-modified medial maxillectomy (EMMM) can reshape the maxillary sinus and avoid a "sumping" effect, preventing secondary bacterial colonization, encouraging dependent drainage, and promoting effective nasal irrigation., Objectives: We describe a modification of the EMMM surgical technique in patients with recalcitrant maxillary sinusitis and perioperative outcomes., Methods: Consecutive adult patients with nonfunctioning maxillary sinuses managed with EMMM were assessed. Primary outcomes were the resolution of the presenting symptom and the absence of mucostasis. Secondary outcomes were early (<90 days) and late (>90 days) morbidity., Results: Fifty-seven patients (51.7  ±  17.5 years, 56.1% female) were assessed. Fifty-two patients had complete resolution of their presenting symptom (91.2% [95% CI: 80.7-97.1]) and 52 patients had an absence of mucostasis (91.2% [95% CI: 80.7-97.1]). Those with persistent crusting were also those with symptoms. Early morbidities included temporary dysesthesia (3.2%), bleeding (1.1%), and pain (3.2%), with no late morbidities., Conclusion: EMMM is a robust approach for salvaging a nonfunctioning maxillary sinus. The procedure enhances nasal irrigation, supplants mucociliary clearance, and discourages dependent mucus retention.

Adenosine receptor (AR) ligands are being developed for metabolic, cardiovascular, neurological, and inflammatory diseases and cancer. The ease of drug discovery is contingent on the availability of pharmacological tools. Fluorescent antagonist ligands for the human A 2A and A 3 ARs were synthesized using two validated pharmacophores, 1,3-dipropyl-8-phenylxanthine and triazolo[1,5-c]quinazolin-5-yl)amine, which were coupled to eight reporter fluorophores: AlexaFluor, JaneliaFluor (JF), cyanine, and near infrared (NIR) dyes. The conjugates were first screened using radioligand binding in HEK293 cells expressing one of the three AR subtypes. The highest affinities at A 2A AR were K i 144-316 nM for 10, 12, and 19, and at A 3 AR affinity of K i 21.6 nM for 19. Specific binding of JF646 conjugate MRS7774 12 to the HEK293 cell surface A 2A AR was imaged using confocal microscopy. Compound 19 MRS7535, a triazolo[1,5-c]quinazolin-5-yl)amine containing a Sulfo-Cy7 NIR dye, was suitable for A 3 AR characterization in whole cells by flow cytometry (K d 11.8 nM), and its bitopic interaction mode with an A 3 AR homology model was predicted. Given its affinity and selectivity (11-fold vs. A 2A AR, ~ 50-fold vs. A 1 AR and A 2B AR) and a good specific-to-nonspecific binding ratio, 19 could be useful for live cell or potentially a diagnostic in vivo NIR imaging tool and/or therapy targeting the A 3 AR., (© 2022. This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.)

( N )-Methanocarba adenosine derivatives (A 3 adenosine receptor (AR) agonists containing bicyclo[3.1.0]hexane replacing furanose) were chain-extended at N 6 and C2 positions with terminal alkenes for ring closure. The resulting macrocycles of 17-20 atoms retained affinity, indicating a spatially proximal orientation of these receptor-bound chains, consistent with molecular modeling of 12 . C2-Arylethynyl-linked macrocycle 19 was more A 3 AR-selective than 2-ether-linked macrocycle 12 (both 5'-methylamides, human (h) A 3 AR affinities ( K i ): 22.1 and 25.8 nM, respectively), with lower mouse A 3 AR affinities. Functional hA 3 AR comparison of two sets of open/closed analogues in β-arrestin2 and G i/o protein assays showed certain signaling preferences divergent from reference agonist Cl-IB-MECA 1 . The potencies of 1 at all three Gα i isoforms were slightly less than its hA 3 AR binding affinity ( K i : 1.4 nM), while the Gα i1 and Gα i2 potencies of macrocycle 12 were roughly an order of magnitude higher than its radioligand binding affinity. Gα i2 -coupling was enhanced in macrocycle 12 (EC 50 2.56 nM, ∼40% greater maximal efficacy than 1 ). Di-O-allyl precursor 18 cyclized to form 19 , increasing the Gα i1 potency by 7.5-fold. The macrocycles 12 and 19 and their open precursors 11 and 18 potently stimulated β-arrestin2 recruitment, with EC 50 values (nM) of 5.17, 4.36, 1.30, and 4.35, respectively, and with nearly 50% greater efficacy compared to 1 . This example of macrocyclization altering the coupling pathways of small-molecule (nonpeptide) GPCR agonists is the first for potent and selective macrocyclic AR agonists. These initial macrocyclic derivatives can serve as a guide for the future design of macrocyclic AR agonists displaying unanticipated pharmacology., Competing Interests: The authors declare no competing financial interest., (© 2023 American Chemical Society.)

Objectives: The aims were to (1) prospectively observe the incidence of bone marrow oedema in asymptomatic adult male domestic professional cricketers during a season and evaluate its relationship to the development of lumbar bone stress injury and (2) further understand the practicalities of implementing a Magnetic Resonance Imaging-based screening program to prevent lumbar bone stress injury in New Zealand cricket., Design: Prospective observational cohort., Methods: Adult male pace bowlers received 6-weekly pre-planned Magnetic Resonance Imaging scans over a single season to determine the presence and intensity of bone marrow oedema in the posterior vertebral arches of the lumbar spine. The participants bowling volume and back pain levels were monitored prospectively., Results: 22 participants (mean age 25.3 years (range 20-32 years)) completed all 4 scans. Ten participants had a prior history of lumbar bone stress injury. Ten participants (45 %, 95 % confidence interval 24-68 %) had bone marrow oedema evident on at least one scan, with 9 (41 %) participants recording a bone marrow oedema intensity ≥ 2 and 5 (23 %) participants demonstrated an intensity ≥ 3. During the study one participant was diagnosed with a lumbar bone stress reaction. No participants developed a lumbar bone stress fracture., Conclusions: Due to the lower incidence of lumbar bone stress injuries in adult bowlers coupled with uncertainty over appropriate threshold values for bone marrow oedema intensity, implementation of a resource intense screening program aimed at identifying adult domestic cricketers at risk of developing a lumbar bone stress injury is not currently supported., Competing Interests: Declaration of interest statement The authors have no conflict of interest to declare. The authors declare that the manuscript submitted to the Journal has not been published elsewhere nor is being considered for publication elsewhere and that the research reported will not be submitted for publication elsewhere until a final decision has been made as to its acceptability by the Journal., (Copyright © 2023 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.)

Background: A considerable volume of possible applications of artificial intelligence (AI) in the field of rhinology exists, and research in the area is rapidly evolving., Objective: This scoping review aims to provide a brief overview of all current literature on AI in the field of rhinology. Further, it aims to highlight gaps in the literature for future rhinology researchers., Methods: OVID MEDLINE (1946-2022) and EMBASE (1974-2022) were searched from January 1, 2017 until May 14, 2022 to identify all relevant articles. The Preferred Reporting Items for Systematic Reviews and Meta-analyses Extension for Scoping Reviews checklist was used to guide the review., Results: A total of 2420 results were identified of which 62 met the eligibility criteria. A further 17 articles were included through bibliography searching, for a total of 79 articles on AI in rhinology. Each year resulted in an increase in the number of publications, from 3 articles published in 2017 to 31 articles published in 2021. Articles were produced by authors from 22 countries with a relative majority coming from the USA (19%), China (19%), and South Korea (13%). Articles were placed into 1 of 5 categories: phenotyping/endotyping (n = 12), radiological diagnostics (n = 42), prognostication (n = 10), non-radiological diagnostics (n = 7), surgical assessment/planning (n = 8). Diagnostic or prognostic utility of the AI algorithms were rated as excellent (n = 29), very good (n = 25), good (n = 7), sufficient (n = 1), bad (n = 2), or was not reported/not applicable (n = 15)., Conclusions: AI is experiencing an increasingly significant role in rhinology research. Articles are showing high rates of diagnostic accuracy and are being published at an almost exponential rate around the world. Utilizing AI in radiological diagnosis was the most published topic of research, however, AI in rhinology is still in its infancy and there are several topics yet to be thoroughly explored.