Metabolic landscape of head and neck squamous cell carcinoma informs a novel kynurenine/Siglec-15 axis in immune escape.

BACKGROUND: Metabolic reprograming and immune escape are two hallmarks of cancer. However, how metabolic disorders drive immune escape in head and neck squamous cell carcinoma (HNSCC) remains unclear. Therefore, the aim of the present study was to investigate the metabolic landscape of HNSCC and its mechanism of driving immune escape. METHODS: Analysis of paired tumor tissues and adjacent normal tissues from 69 HNSCC patients was performed using liquid/gas chromatography-mass spectrometry and RNA-sequencing. The tumor-promoting function of kynurenine (Kyn) was explored in vitro and in vivo. The downstream target of Kyn was investigated in CD8+ T cells. The regulation of CD8+ T cells was investigated after Siglec-15 overexpression in vivo. An engineering nanoparticle was established to deliver Siglec-15 small interfering RNA (siS15), and its association with immunotherapy response were investigated. The association between Siglec-15 and CD8+ programmed cell death 1 (PD-1)+ T cells was analyzed in a HNSCC patient cohort. RESULTS: A total of 178 metabolites showed significant dysregulation in HNSCC, including carbohydrates, lipids and lipid-like molecules, and amino acids. Among these, amino acid metabolism was the most significantly altered, especially Kyn, which promoted tumor proliferation and metastasis. In addition, most immune checkpoint molecules were upregulated in Kyn-high patients based on RNA-sequencing. Furthermore, tumor-derived Kyn was transferred into CD8+ T cells and induced T cell functional exhaustion, and blocking Kyn transporters restored its killing activity. Accroding to the results, mechanistically, Kyn transcriptionally regulated the expression of Siglec-15 via aryl hydrocarbon receptor (AhR), and overexpression of Siglec-15 promoted immune escape by suppressing T cell infiltration and activation. Targeting AhR in vivo reduced Kyn-mediated Siglec-15 expression and promoted intratumoral CD8+ T cell infiltration and killing capacity. Finally, a NH2-modified mesoporous silica nanoparticle was designed to deliver siS15, which restored CD8+ T cell function status and enhanced anti-PD-1 efficacy in tumor-bearing immunocompetent mice. Clinically, Siglec-15 was positively correlated with AhR expression and CD8+PD-1+ T cell infiltration in HNSCC tissues. CONCLUSIONS: The findings describe the metabolic landscape of HNSCC comprehensively and reveal that the Kyn/Siglec-15 axis may be a novel potential immunometabolism mechanism, providing a promising therapeutic strategy for cancers.

Enrichment of Geogenic Organoiodine Compounds in Alluvial-Lacustrine Aquifers: Molecular Constraints by Organic Matter.

Organoiodine compounds (OICs) are the dominant iodine species in groundwater systems. However, molecular mechanisms underlying the geochemical formation of geogenic OICs-contaminated groundwater remain unclear. Based upon multitarget field monitoring in combination with ultrahigh-resolution molecular characterization of organic components for alluvial-lacustrine aquifers, we identified a total of 939 OICs in groundwater under reducing and circumneutral pH conditions. In comparison to those in water-soluble organic matter (WSOM) in sediments, the OICs in dissolved organic matter (DOM) in groundwater typically contain fewer polycyclic aromatics and polyphenol compounds but more highly unsaturated compounds. Consequently, there were two major sources of geogenic OICs in groundwater: the migration of the OICs from aquifer sediments and abiotic reduction of iodate coupled with DOM iodination under reducing conditions. DOM iodination occurs primarily through the incorporation of reactive iodine that is generated by iodate reduction into highly unsaturated compounds, preferably containing hydrophilic functional groups as binding sites. It leads to elevation of the concentration of the OICs up to 183 µg/L in groundwater. This research provides new insights into the constraints of DOM molecular composition on the mobilization and enrichment of OICs in alluvial-lacustrine aquifers and thus improves our understanding of the genesis of geogenic iodine-contaminated groundwater systems.

Epithelium-derived kallistatin promotes CD4+ T-cell chemotaxis to TH2-type inflammation in chronic rhinosinusitis.

BACKGROUND: The function of kallistatin in airway inflammation, particularly chronic rhinosinusitis with nasal polyps (CRSwNP), has not been elucidated. OBJECTIVE: We sought to investigate the role of kallistatin in airway inflammation. METHODS: Kallistatin and proinflammatory cytokine expression levels were detected in nasal polyps. For the in vivo studies, we constructed the kallistatin-overexpressing transgenic mice to elucidate the role of kallistatin in airway inflammation. Furthermore, the levels of plasma IgE and proinflammatory cytokines in the airways were evaluated in the kallistatin-/- rat in vivo model under a type 2 inflammatory background. Finally, the Notch signaling pathway was explored to understand the role of kallistatin in CRSwNP. RESULTS: We showed that the expression of kallistatin was significantly higher in nasal polyps than in the normal nasal mucosa and correlated with IL-4 expression. We also discovered that the nasal mucosa of kallistatin-overexpressing transgenic mice expressed higher levels of IL-4 expression, associating to TH2-type inflammation. Interestingly, we observed lower IL-4 levels in the nasal mucosa and lower total plasma IgE of the kallistatin-/- group treated with house dust mite allergen compared with the wild-type house dust mite group. Finally, we observed a significant increase in the expression of Jagged2 in the nasal epithelium cells transduced with adenovirus-kallistatin. This heightened expression correlated with increased secretion of IL-4, attributed to the augmented population of CD4+CD45+Notch1+ T cells. These findings collectively may contribute to the induction of TH2-type inflammation. CONCLUSIONS: Kallistatin was demonstrated to be involved in the CRSwNP pathogenesis by enhancing the TH2 inflammation, which was found to be associated with more expression of IL-4, potentially facilitated through Jagged2-Notch1 signaling in CD4+ T cells.

Outcomes of endoscopic sinus surgery in patients with central compartment atopic disease.

Background: Central compartment atopic disease (CCAD) is a subtype of chronic rhinosinusitis (CRS). Research focusing on the endoscopic sinus surgery (ESS) outcomes of CCAD is limited. This study aimed to evaluate the outcomes of ESS in CCAD and compared to 2 following subtypes: chronic rhinosinusitis with nasal polyps (CRSwNP) and concomitant polypoid disease in the central compartment (CRSwNP/CC) and CRSwNP not otherwise specified (CRSwNP NOS). Methods: This case-control study enrolled patients with bilateral CRSwNP who underwent ESS and had at least 1 year of follow-up. Patients were classified into CCAD, CRSwNP/CC, and CRSwNP NOS. The demographic data, preoperative disease severity, and surgery outcomes, including CRS control status, endoscopic score, and symptom scores at 1 year postoperatively, were collected. We defined well controlled and partly controlled as appropriate disease control. Results: This study screened 259 patients and enrolled 138 patients with complete medical records and 1-year follow-up (CCAD N = 51, CRSwNP/CC N = 55, CRSwNP NOS N = 32). Among them, appropriate disease control was achieved in 84.3% of patients (43/51) in the CCAD group, 69.1% (38/55) in the CRSwNP/CC group, and 93.7% (30/32) in the CRSwNP NOS group (P = 0.029). Then we performed post-hoc analysis using appropriate disease control and uncontrolled. There was a significant difference between CRSwNP/CC and CRSwNP NOS (P = 0.007), but no significant difference compared CCAD group to CRSwNP/CC group (P = 0.065) and CRSwNP NOS group (P = 0.199). There were significant differences in endoscopic E-score among groups (P < 0.001). In post-hoc analysis, we found that CRSwNP/CC (Median [IQR], 33.32 [42.14]) had a significantly worse E-score than CCAD (8.33 [16.67]) and CRSwNP NOS (4.17 [8.30]). Also, postoperative olfactory visual analog scale (VAS) scores significantly differed among groups (P = 0.043). However, post-hoc analysis showed no difference between any 2 groups. There were no differences in postoperative VAS scores of obstruction (P = 0.159), rhinorrhea (P = 0.398), and headache/facial pain (P = 0.092). Conclusion: Most CCAD patients had good surgical outcomes 1 year after surgery. Meanwhile, the CRSwNP/CC group had the fewest patients under appropriate disease control.

Arsenite S-Adenosylmethionine Methyltransferase Is Responsible for Antimony Biomethylation in Nostoc sp. PCC7120.

Antimony (Sb) biomethylation is an important but uninformed process in Sb biogeochemical cycling. Methylated Sb species have been widely detected in the environment, but the gene and enzyme for Sb methylation remain unknown. Here, we found that arsenite S-adenosylmethionine methyltransferase (ArsM) is able to catalyze Sb(III) methylation. The stepwise methylation by ArsM forms mono-, di-, and trimethylated Sb species. Sb(III) is readily coordinated with glutathione, forming the preferred ArsM substrate which is anchored on three conserved cysteines. Overexpressing arsM in Escherichia coli AW3110 conferred resistance to Sb(III) by converting intracellular Sb(III) into gaseous methylated species, serving as a detoxification process. Methylated Sb species were detected in paddy soil cultures, and phylogenetic analysis of ArsM showed its great diversity in ecosystems, suggesting a high metabolic potential for Sb(III) methylation in the environment. This study shows an undiscovered microbial process methylating aqueous Sb(III) into the gaseous phase, mobilizing Sb on a regional and even global scale as a re-emerging contaminant.

Surgical Outcomes of Standardized Endoscopical Deep Medial Orbital Decompression in Dysthyroid Optic Neuropathy.

INTRODUCTION: The aim of the study was to standardize the endoscopic deep medial orbital decompression surgery for better relief of optic nerve compression in dysthyroid optic neuropathy (DON). METHODS: A total of 128 eyes from patients received the standardized endoscopic deep medial orbital decompression surgery were recruited in this study. The efficacy of the procedure was assessed at a 1-month follow-up by the best-corrected visual acuity (VA), visual field (VF), and visual evoked potential (VEP). Clinical data were collected to explore the factors that affected visual recovery. Oxygen saturation of retinal blood vessels, retinal thickness, and vessel density were measured to demonstrate the potential recovery mechanisms. RESULTS: After surgery, the ratio of extraocular muscle volume in the orbital apex to orbital apex volume significantly decreased from 44.32 ± 22.31% to 36.82 ± 12.02% (p < 0.001). 96.87% of eyes' final VA improved; average VA improved from 0.93 ± 0.73 to 0.50 ± 0.60 at 1 week (p < 0.001) and 0.40 ± 0.53 at 1 month (p < 0.001). Postoperatively, VF and VEP also improved, the oxygen saturation of retinal arteries increased, and the retinal thickness was reduced. Preoperative VA, visual impairment duration, and clinical activity score evaluation were associated with visual recovery. CONCLUSION: In this study, we standardized the endoscopic deep medial orbital decompression, of which key point was to relieve pressure in the orbital apex and achieved satisfactory visual recovery in DON patients.

Antimony Isotope Fractionation during Adsorption on Iron (Oxyhydr)oxides.

The fate of antimony (Sb) is strongly affected by adsorption, yet Sb isotope fractionation and the associated mechanism have not been widely reported. Here we experimentally investigated the process of Sb(V) adsorption on iron (oxyhydr)oxides and the associated isotope effects. Sb isotope fractionation occurs during adsorption (Δ123Sbsolution-mineral = 1.20 ± 0.02‰ for ferrihydrite and 2.35 ± 0.04‰ for goethite). Extended X-ray absorption fine structure (EXAFS) analysis shows that Sb(V) adsorption on iron (oxyhydr)oxides occurs via inner-sphere surface complexation, including mononuclear bidentate edge-sharing (2E) and binuclear bidentate corner-sharing (2C) complexes. A longer atom distance of Sb-Fe in ferrihydrite leads to less Sb isotope fractionation during Sb adsorption than in goethite. The Gibbs free energy and Mayer bond order were calculated based on density functional theory (DFT) and suggested that the strength of the bonding environment can be summarized as Sb(OH)6- > 2E > 2C. In turn, the bonding environment indicates the mechanism of Sb isotope fractionation during the process. This study reveals that Sb isotope fractionation occurs during Sb(V) adsorption onto iron (oxyhydr)oxides, providing a basis for the future study of Sb isotopes and further understanding of the fractionation mechanism.

Developing the surgeon-machine interface: using a novel instance-segmentation framework for intraoperative landmark labelling.

Introduction: The utilisation of artificial intelligence (AI) augments intraoperative safety, surgical training, and patient outcomes. We introduce the term Surgeon-Machine Interface (SMI) to describe this innovative intersection between surgeons and machine inference. A custom deep computer vision (CV) architecture within a sparse labelling paradigm was developed, specifically tailored to conceptualise the SMI. This platform demonstrates the ability to perform instance segmentation on anatomical landmarks and tools from a single open spinal dural arteriovenous fistula (dAVF) surgery video dataset. Methods: Our custom deep convolutional neural network was based on SOLOv2 architecture for precise, instance-level segmentation of surgical video data. Test video consisted of 8520 frames, with sparse labelling of only 133 frames annotated for training. Accuracy and inference time, assessed using F1-score and mean Average Precision (mAP), were compared against current state-of-the-art architectures on a separate test set of 85 additionally annotated frames. Results: Our SMI demonstrated superior accuracy and computing speed compared to these frameworks. The F1-score and mAP achieved by our platform were 17% and 15.2% respectively, surpassing MaskRCNN (15.2%, 13.9%), YOLOv3 (5.4%, 11.9%), and SOLOv2 (3.1%, 10.4%). Considering detections that exceeded the Intersection over Union threshold of 50%, our platform achieved an impressive F1-score of 44.2% and mAP of 46.3%, outperforming MaskRCNN (41.3%, 43.5%), YOLOv3 (15%, 34.1%), and SOLOv2 (9%, 32.3%). Our platform demonstrated the fastest inference time (88ms), compared to MaskRCNN (90ms), SOLOV2 (100ms), and YOLOv3 (106ms). Finally, the minimal amount of training set demonstrated a good generalisation performance -our architecture successfully identified objects in a frame that were not included in the training or validation frames, indicating its ability to handle out-of-domain scenarios. Discussion: We present our development of an innovative intraoperative SMI to demonstrate the future promise of advanced CV in the surgical domain. Through successful implementation in a microscopic dAVF surgery, our framework demonstrates superior performance over current state-of-the-art segmentation architectures in intraoperative landmark guidance with high sample efficiency, representing the most advanced AI-enabled surgical inference platform to date. Our future goals include transfer learning paradigms for scaling to additional surgery types, addressing clinical and technical limitations for performing real-time decoding, and ultimate enablement of a real-time neurosurgical guidance platform.

Endotyping Difficult-to-Treat Chronic Rhinosinusitis with Nasal Polyps by Structured Histopathology.

INTRODUCTION: This study aimed to identify the histopathologic characteristics associated with difficult-to-treat chronic rhinosinusitis with nasal polyps (CRSwNPs), enabling physicians to predict the risk of poor outcome after endoscopic sinus surgery (ESS). METHODS: A prospective cohort study performed at the First Affiliated Hospital of Sun Yat-sen University between January 2015 and December 2018 with CRSwNP patients who underwent ESS. Polyp specimens were collected during surgery and were subjected to structured histopathological evaluation. Difficult-to-treat CRSwNPs were determined at 12-15 months post-operation according to the European Position Paper. Multiple logistic regression model was used to assess the association between histopathological parameters and the difficult-to-treat CRSwNP. RESULTS: Among 174 subjects included in the analysis, 49 (28.2%) were classified with difficult-to-treat CRSwNP, which had higher numbers of total inflammatory cells, tissue eosinophils, and percentages of eosinophil aggregates and Charcot-Leyden crystals (CLC) formation but a lower number of interstitial glands than the nondifficult-to-treat CRSwNP. Inflammatory cell infiltration (adjusted OR: 1.017), tissue eosinophilia (adjusted OR: 1.005), eosinophil aggregation (adjusted OR: 3.536), and CLC formation (adjusted OR: 6.972) were independently associated with the difficult-to-treat outcome. Furthermore, patients with tissue eosinophil aggregation and CLC formation had an increasingly higher likelihood of uncontrolled disease versus those with tissue eosinophilia. CONCLUSION: The difficult-to-treat CRSwNP appears to be characterized by increased total inflammatory infiltrates, tissue eosinophilia, eosinophil aggregation, and CLC formation in structured histopathology.

PM2.5 Increases Systemic Inflammatory Cells and Associated Disease Risks by Inducing NRF2-Dependent Myeloid-Biased Hematopoiesis in Adult Male Mice.

Although PM2.5 (fine particles with aerodynamic diameter <2.5 µm) exposure shows the potential to impact normal hematopoiesis, the detailed alterations in systemic hematopoiesis and the underlying mechanisms remain unclear. For hematopoiesis under steady-state or stress conditions, nuclear factor erythroid 2-related factor 2 (NRF2) is essential for regulating hematopoietic processes to maintain blood homeostasis. Herein, we characterized changes in the populations of hematopoietic stem progenitor cells and committed hematopoietic progenitors in the lungs and bone marrow (BM) of wild-type and Nrf2-/- C57BL/6J male mice. PM2.5-induced NRF2-dependent biased hematopoiesis toward myeloid lineage in the lungs and BM generates excessive numbers of various inflammatory immune cells, including neutrophils, monocytes, and platelets. The increased population of these immune cells in the lungs, BM, and peripheral blood has been associated with observed pulmonary fibrosis and high disease risks in an NRF2-dependent manner. Therefore, although NRF2 is a protective factor against stressors, upon PM2.5 exposure, NRF2 is involved in stress myelopoiesis and enhanced PM2.5 toxicity in pulmonary injury, even leading to systemic inflammation.

Mechanism and controlling factors on rapid methylmercury degradation by ligand-enhanced Fenton-like reaction at circumneutral pH.

Methylmercury (MeHg), derived from industrial processes and microbial methylation, is still a worldwide environmental concern. A rapid and efficient strategy is necessary for MeHg degradation in waste and environmental waters. Here, we provide a new method with ligand-enhanced Fenton-like reaction to rapidly degrade MeHg under neutral pH. Three common chelating ligands were selected (nitriloacetic acid (NTA), citrate, and ethylenediaminetetraacetic disodium (EDTA)) to promote the Fenton-like reaction and degradation of MeHg. Results showed that MeHg can be rapidly degraded, with the following efficiency sequence: EDTA > NTA > citrate. Scavenger addition demonstrated that hydroxyl radical (▪OH), superoxide radical (O2▪-), and ferryl (FeⅣO2+) were involved in MeHg degradation, and their relative contributions highly depended on ligand type. Degradation product and total Hg analysis suggested that Hg(Ⅱ) and Hg0 were generated with the demethylation of MeHg. Further, environmental factors, including initial pH, organic complexation (natural organic matter and cysteine), and inorganic ions (chloride and bicarbonate) on MeHg degradation, were investigated in NTA-enhanced system. Finally, rapid MeHg degradation was validated for MeHg-spiked waste and environmental waters. This study provided a simple and efficient strategy for MeHg remediation in contaminated waters, which is also helpful for understanding its degradation in the natural environment.

Colloidal iron species driven enhanced H2O2 decomposition into hydroxyl radicals for efficient removal of methylene blue from water.

Colloids are wide-spread in natural waters and colloid-facilitated transport via adsorption was established as the most important mechanism for the mobilization of aqueous contaminants. This study reports another possible, but reasonable, role of colloids for the contaminants driven by redox reactions. Under the same conditions (pH 6.0, 0.3 ml 30% H2O2, and 25 °C), the degradation efficiencies of methylene blue (MB) at 240 min over Fe colloid, Fe ion, Fe oxide and Fe(OH)3 were 95.38%, 42.66%, 4.42% and 9.40%. We suggested that, Fe colloid can promote the H2O2 based in-situ chemical oxidation process (ISCO) compared with other iron species such as Fe(Ⅲ) ion, Fe oxide and Fe(OH)3 in natural water. Furthermore, the MB removal via adsorption by Fe colloid was only 1.74% at 240 min. Hence, the occurrence, behavior and fate of MB in Fe colloid containing natural water system mainly depends on the reduction-oxidation rather than adsorption-desorption process. Based on the mass balance of colloidal iron species and characterization of iron configurations distribution, Fe oligomers were the active and dominant components for Fe colloid-driven enhanced H2O2 activation among three types of Fe species. The quick and steady conversion of Fe(III) to Fe(II) was proven to be reason why Fe colloid can efficiently react with H2O2 to produce hydroxyl radicals.

Efficient and selective removal of Hg(II) from water using recyclable hierarchical MoS2/Fe3O4 nanocomposites.

Developing practical and cost-effective adsorbents with satisfactory mercury (Hg) remediation capability is indispensable for aquatic environment safety and public health. Herein, a recyclable hierarchical MoS2/Fe3O4 nanocomposite (by in-situ growth of MoS2 nanosheets on the surface of Fe3O4 nanospheres) is presented for the selective removal of Hg(II) from aquatic samples. It exhibited high adsorption capacity (∼1923.5 mg g -1), fast kinetics (k2 ∼ 0.56 mg g -1 min-1), broad working pH range (2-11), excellent selectivity (Kd > 1.0 × 107 mL g -1), and great reusability (removal efficiency > 90% after 20 cycles). In particular, removal efficiencies of up to ∼97% for different Hg(II) concentrations (10-1000 µg L -1) in natural water and industrial effluents confirmed the practicability of MoS2/Fe3O4. The possible mechanism for effective Hg(II) removal was discussed by a series of characterization analyses, which was attributed to the alteration of the MoS2 structure and the surface coordination of Hg-S. The accessibility of surface sulfur sites and the diffusion of Hg(II) in the solid-liquid system were enhanced due to the advantage of the expanded interlayer spacing (0.96 nm) and the hierarchical structure. This study suggests that MoS2/Fe3O4 is a promising material for Hg(II) removal in actual scenarios and provides a feasible approach by rationally constructing hierarchical structures to promote the practical applications of MoS2 in sustainable water treatments.

Disposable Polypropylene Face Masks: A Potential Source of Micro/Nanoparticles and Organic Contaminates in Humans.

We have been effectively protected by disposable propylene face masks during the COVID-19 pandemic; however, they may pose health risks due to the release of fine particles and chemicals. We measured micro/nanoparticles and organic chemicals in disposable medical masks, surgical masks, and (K)N95 respirators. In the breathing-simulation experiment, no notable differences were found in the total number of particles among mask types or between breathing intensities. However, when considering subranges, <2.5 µm particles accounted for ∼90% of the total number of micro/nanoparticles. GC-HRMS-based suspect screening tentatively revealed 79 (semi)volatile organic compounds in masks, with 18 being detected in ≥80% of samples and 44 in ≤20% of samples. Three synthetic phenolic antioxidants were quantified, and AO168 reached a median concentration of 2968 ng/g. By screening particles collected from bulk mask fabrics, we detected 18 chemicals, including four commonly detected in masks, suggesting chemical partition between the particles and the fabric fibers and chemical exposure via particle inhalation. These particles and chemicals are believed to originate from raw materials, intentionally and nonintentionally added substances in mask production, and their transformation products. This study highlights the need to study the long-term health risks associated with mask wearing and raises concerns over mask quality control.

Relationship between Eosinophilic and Neutrophilic Inflammation in Chinese Chronic Rhinosinusitis with Nasal Polyps.

INTRODUCTION: Chronic rhinosinusitis with nasal polyps (CRSwNPs) in China is characterized by a mixed eosinophilic-neutrophilic inflammation, linking to a more heterogeneous clinical phenotype. However, the relationship between eosinophilic and neutrophilic inflammation in Chinese patients with CRSwNP remains largely unknown. We aimed to further characterize the correlation between neutrophils with eosinophils in relation to clinical characters and disease control status after endoscopic sinus surgery (ESS). METHODS: A total of 242 patients were recruited and stratified based on tissue (≥10%) eosinophilia and (≥20/per high-power field) neutrophilia. Clinical characteristics and disease control status were compared between subgroups. Associations between tissue eosinophils and neutrophils were analyzed. RESULTS: The uncontrolled patients accounted for 41.3%, 41.3%, 17.1%, and 22.2% in subjects with concomitant tissue eosinophilia and neutrophilia (EN-high), isolated eosinophilia (E-high), isolated neutrophilia (N-high), and no eosinophilia and neutrophilia (EN-low), respectively. Positive correlations between tissue eosinophils and neutrophils were observed in patients with CRSwNP as well as in EN-high and N-high subgroups but not in E-high and EN-low subgroups. The EN-high subgroup had higher tissue eosinophil numbers than the other three subgroups. Both EN-high and E-high subgroups had higher rates of uncontrolled subjects than the N-high and EN-low subgroups; however, there was no difference in the rate of uncontrolled subjects between EN-high and E-high subgroups and between N-high and EN-low subgroups. CONCLUSION: Tissue neutrophils might have a potential interaction and mutual promotion effect with eosinophils in CRSwNP. However, tissue neutrophilia would not pose significant risk for poor disease control after ESS. Further larger, prospective studies are needed to confirm our findings.

Cluster analysis of patients with chronic rhinosinusitis and asthma after endoscopic sinus surgery.

BACKGROUND: Patients with chronic rhinosinusitis with nasal polyps and asthma (CRSwAS) are highly heterogenous in severity and prognosis. The clinical phenotypes and inflammatory endotypes of CRSwAS and their association with outcomes of endoscopic sinus surgery (ESS) have not been fully studied yet. OBJECTIVE: We aimed to find out the clinical phenotypes of CRSwAS and explore their relationship with ESS outcomes using cluster analysis. METHODS: We recruited 103 consecutive adult patients with CRSwAS who had undergone ESS and been followed up for more than 1 year. For cluster analysis, we collected the data from 63 variables pertaining to demographic characteristics, preoperative disease status, surgical techniques, postoperative medical treatment, and outcomes. Eosinophilic CRS was defined as greater than or equal to 10 eosinophils/high-power field, and sinus computed tomography was evaluated by Lund-Mackay sinus computed tomography score (LM score). RESULTS: We screened 92 eligible patients and 13 preoperative variables for balanced iterative reducing and clustering using hierarchies cluster analysis. Patients with CRSwAS were divided into 4 clusters with distinct ESS outcomes: (1) cluster 1, characterized by aspirin-exacerbated respiratory disease, eosinophilic CRS, high preoperative LM score, moderate-to-severe asthma, and uncontrolled CRS after ESS; (2) cluster 2, characterized as having female dominance (66.67%), non-aspirin-exacerbated respiratory disease, eosinophilic CRS, high preoperative LM score, moderate-to-severe asthma, and uncontrolled CRS after ESS; (3) cluster 3, characterized as having female dominance (95.83%), noneosinophilic CRS, low preoperative LM score, moderate asthma, and controlled CRS after ESS; and (4) cluster 4, characterized as men-only, smoker, noneosinophilic CRS, low preoperative LM score, mild asthma, and controlled CRS after ESS. CONCLUSION: CRSwAS has distinct clusters, each corresponding to unique clinical and inflammatory characteristics and ESS outcomes.

Clinical characteristics of central compartment atopic disease in Southern China.

BACKGROUND: Central compartment atopic disease (CCAD) is a newly reported subset of chronic rhinosinusitis. It was considered associated with inhalant antigen. However, CCAD in Chinese population is not fully studied yet. DESIGN: Prospective cohort study. OBJECTIVE: This study aimed to describe the clinical manifestations of CCAD and compared the following two subtypes: sinonasal polyps and concomitant polypoid disease in the central compartment (CRSwNP/CC) and CRSwNP not otherwise specified (CRSwNP NOS). Also, we compared the clinical manifestations of atopy CCAD and non-atopy CCAD. METHODS: We consecutively enrolled CRSwNP patients without prior sinus surgery, and assessed the nasal endoscopy and computed tomography of the paranasal sinuses. Allergy was confirmed by skin or serum testing. Eosinophilic CRSwNP (ECRS) was considered as tissue eosinophils to total inflammatory cells >10%. RESULTS: We enrolled a total of 116 patients, including 39 with CCAD, 38 with CRSwNP/CC and 39 with CRSwNP NOS. Atopy was detected in 37.1% of the CCAD group, an incidence showing no significant difference from those in the other two groups (37.1% in the CRSwNP/CC group, 31.0% in the CRSwNP NOS group; p = 0.846). However, the incidence of ECRS in the CCAD group was the highest among the different groups (97.4% in the CCAD group vs. 67.6% in the CRSwNP/CC group vs. 35.1% in the CRSwNP NOS group; p = 0.000). In addition, the incidence of asthma in the CCAD group (33.3%) was significantly higher than that in the CRSwNP NOS group (10.3%), but quite similar to CRSwNP/CC (34.2%). In the subgroup analysis of CCAD, only total serum IgE and sIgE demonstrated significant differences between atopy CCAD and non-atopy CCAD. CONCLUSION: CCAD in Southern China may associate with asthma and significant eosinophilia, with a lower incidence of systemic allergy based on skin and serum testing.

Therapeutic potential of recombinant human basic fibroblast growth factor on postoperative patients with chronic rhinosinusitis with nasal polyps.

OBJECTIVES: To explore the effect of intranasal administration of recombinant human basic fibroblast growth factor (rh-bFGF) on postoperative chronic rhinosinusitis with nasal polyps (CRSwNP) patients. DESIGN: A prospective, randomised, controlled, single-blinded trial. SETTING AND PARTICIPANTS: Seventy-five hospitalised patients who met the criteria of primary bilateral CRSwNP were enrolled from March 2020 to January 2021. MAIN OUTCOME MEASURES: Visual analogue scale, 22-item Sino-Nasal Outcome Test, Lund-Kennedy (L-K) system and scanning electron microscopy and quantitative real-time polymerase chain reaction. RESULTS: Seventy-five patients with CRSwNP were randomly assigned to three groups, and 72 patients completed the 1-month medication regimen and 1-year follow-up. Rh-bFGF nasal-spray and drop application reduced general nasal VAS scores within 2 weeks after endoscopic sinus surgery (ESS) compared to the control group. In contrast, only rh-bFGF nasal-drops reduced SNOT-22 scores at 2 weeks and 1 year compared with the control group. A significant reduction in the endoscopic L-K score was observed in the rh-bFGF nasal-spray and drop group compared with the control group. This is primarily because rh-bFGF promotes cilia growth in the nasal mucosal epithelium after the operation, as illustrated by scanning electron microscopy and expression of CP110, Tap73 and Foxj1 mRNA. For eosinophilic CRSwNP, the general VAS score of rh-bFGF nasal-drops was more obviously reduced compared to the control group after ESS. A similar trend was observed for L-K score. CONCLUSIONS: Rh-bFGF nasal-drops and sprays can quickly and effectively relieve postoperative symptoms and improve long-term prognosis of patients with CRSwNP. Moreover, rh-bFGF nasal-drops is also an effective method for postoperative patients with eosinophilic CRSwNP.

Deep learning-based prediction of treatment prognosis from nasal polyp histology slides.

BACKGROUND: Histopathology of nasal polyps contains rich prognostic information, which is difficult to extract objectively. In the present study, we aimed to develop a prognostic indicator of patient outcomes by analyzing scanned conventional hematoxylin and eosin (H&E)-stained slides alone using deep learning. METHODS: An interpretable supervised deep learning model was developed using 185 H&E-stained whole-slide images (WSIs) of nasal polyps, each from a patient randomly selected from the pool of 232 patients who underwent endoscopic sinus surgery at the First Affiliated Hospital of Sun Yat-Sen University (internal cohort). We internally validated the model on a holdout dataset from the internal cohort (47 H&E-stained WSIs) and externally validated the model on 122 H&E-stained WSIs from the Seventh Affiliated Hospital of Sun Yat-Sen University and the University of Hong Kong-Shenzhen Hospital (external cohort). A poor prognosis score (PPS) was established to evaluate patient outcomes, and then risk activation mapping was applied to visualize the histopathological features underlying PPS. RESULTS: The model yielded a patient-level sensitivity of 79.5%, and specificity of 92.3%, with areas under the receiver operating characteristic curve of 0.943, on the multicenter external cohort. The predictive ability of PPS was superior to that of conventional tissue eosinophil number. Notably, eosinophil infiltration, goblet cell hyperplasia, glandular hyperplasia, squamous metaplasia, and fibrin deposition were identified as the main underlying features of PPS. CONCLUSIONS: Our deep learning model is an effective method for decoding pathological images of nasal polyps, providing a valuable solution for disease prognosis prediction and precise patient treatment.

Risk Factors and Characteristics of the Recurrence of Juvenile Nasopharyngeal Angiofibroma: A 22-Year Experience With 123 Cases at a Tertiary Center.

OBJECTIVES: Despite the efficacy of surgical treatments, the high rate of recurrence in juvenile nasopharyngeal angiofibroma (JNA) after surgery remains an unresolved problem. The present study comprehensively analyzed the risk factors and characteristics of JNA recurrence, providing clinical guidance for reducing recurrence. METHODS: A total of 123 patients who underwent surgery for JNA between 1997 and 2019 at a single hospital were analyzed retrospectively. Univariate and multivariate analyses were used to assess the clinical risk factors for the recurrence of JNA. The relapse-free survival and annual cumulative recurrence rates were analyzed for subgroups defined according to clinical parameters. RESULTS: After screening, 78 of the 123 patients were included in the present study. The main risk factors associated with JNA recurrence included the year of diagnosis, tumor size, sphenoid bone invasion, Radkowski stage, surgical approach, and intraoperative bleeding. Importantly, the surgical approach and sphenoid bone invasion were independent prognostic factors affecting recurrence. Patients who underwent endoscopic surgery without sphenoid bone invasion exhibited longer relapse-free survival. In the present study, the overall cumulative recurrence rate of JNA was 38.7%, and recurrence occurred mainly in the first year after the initial surgery. CONCLUSION: Endoscopic surgery achieved better relapse-free survival in JNA patients, and patients with sphenoid bone invasion should be carefully explored to avoid residual JNA. The recurrence rate of JNA differed among subgroups defined based on clinical parameters and was highest in the first year after surgery. Computed tomography or magnetic resonance imaging, along with close follow-up, should be performed strictly within 1 year after the primary operation.