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Background: Mucin over‐secretion is a significant characteristic of chronic rhinosinusitis with nasal polyps (CRSwNP). This study aimed to investigate the relationship between Th2 cytokines and MUC5AC or MUC5B, and the mechanism of mucin over‐secretion in the type‐2 inflammatory endotype of CRSwNP. Methods: Main Th‐cell cytokines, associated mediators, and mucins were determined in the homogenates of nasal polyp samples from 21 CRSwNP patients and inferior turbinate samples from 8 controls, by ELISA or UniCAP system. Secretion of MUC5AC and MUC5B was measured in the supernatants of IL‐5, IL‐4, or IL‐13 primed nasal polyp fragments. Co‐localization of MUC5AC, MUC5B, and IL‐4 receptor α (IL‐4Rα) in CRSwNP and controls was evaluated by immunohistochemistry. Gene expression of IL‐4Rα in the samples was measured by real‐time reverse transcription‐polymerase chain reaction. Results: Baseline protein levels of the Th2‐cytokines IL‐4, IL‐5, and IL‐13, and mucins MUC5AC and MUC5B were significantly higher in the IL‐5(+) CRSwNP group, compared to control and IL‐5(−) CRSwNP groups. MUC5AC and MUC5B secretions were significantly increased in IL‐4‐ or IL‐13‐primed, but not IL‐5‐primed fragments of nasal polyps. Immuno‐stained serial sections demonstrated that IL‐4Rα was widely expressed in the epithelium and submucosal glands in control and nasal polyp tissues. Gene expression of IL‐4Rα was elevated in nasal polyp tissues, specifically in the IL‐5(+) CRSwNP group. Conclusions: In type‐2 inflammatory nasal polyps, characterized by the tissue expression of IL‐5, MUC5AC and MUC5B are overexpressed. Both IL‐4 and IL‐13 may upregulate mucin expression via IL‐4Rα, which is also overexpressed in IL‐5(+) CRSwNP. The highlight of this study lies in the finding that Th2 inflammatory patterns are strongly related to mucin hypersecretion in endotypes of CRSwNP defined by IL‐5. In the present study, we found that IL‐4, IL‐13, MUC5AC and MUC5B were overexpressed in IL‐5(+) CRSwNP. Th2 associated mediators IgE and ECP were significantly increased in IL‐5(+) CRSwNP as well and intimately corelated to mucin hypersecretion. Both IL‐4 and IL‐13 may upregulate mucin expression via their common receptor, IL‐4Rα, which is also overexpressed in IL‐5(+) CRSwNP. [ABSTRACT FROM AUTHOR]

Extensively based on evidence gained from experimental animal models, the transient receptor potential vanilloid receptor type 1 (TRPV1)-activator capsaicin is regarded as a valuable tool in the research on neurogenic inflammation. Although capsaicin-related drugs gained renewed interest as a therapeutic tool, there is also controversy as whether neurogenic inflammation actually takes place in humans. In this study, we verified the involvement of capsaicin in vascular responses that are regarded to be implicated in the cascade of neurogenic inflammatory mechanisms. By means of ex vivo functional experiments on human nasal mucosal vascular beds, the effect and mechanism of action of capsaicin was assessed in the absence and presence of various agents that interfere with potentially related transduction pathways. Ten micromolars of capsaicin induced vasodilatations that were reduced by the selective EP prostanoid receptor antagonist SC19220 (10 μM) and almost abolished by the selective COX-2 inhibitor NS398 (1 μM) and the EP receptor agonist sulprostone (0.1-10 nM), but not affected by the TRPV1-antagonists capsazepine (5 μM), the neurokinin NK receptor antagonist GR20517A (1 μM), and the calcitonin-gene-related peptide (CGRP) receptor antagonist CGRP8-37 (100 nM). Spontaneously released PGE and PGD levels were significantly reduced in the presence of capsaicin. In conclusion, capsaicin-at concentrations clinically applied or under investigation for diverse disease backgrounds-induces a vasodilatory response in human nasal mucosa via a mechanism involving TRPV1-independent reduction of PGE production by modulation of COX-2 enzymatic activity. These vasodilatations can be suppressed by the EP receptor agonist sulprostone at subnanomolar concentrations. [ABSTRACT FROM AUTHOR]

Background: Cigarette smoke (CS) is known to initiate a cascade of mediator release and accumulation of immune and inflammatory cells in the lower airways. We investigated and compared the effects of CS on upper and lower airways, in a mouse model of subacute and chronic CS exposure.Methods: C57BL/6 mice were whole-body exposed to mainstream CS or air, for 2, 4 and 24 weeks. Bronchoalveolar lavage fluid (BAL) was obtained and tissue cryosections from nasal turbinates were stained for neutrophils and T cells. Furthermore, we evaluated GCP-2, KC, MCP-1, MIP-3alpha, RORc, IL-17, FoxP3, and TGF-beta1 in nasal turbinates and lungs by RT-PCR.Results: In both upper and lower airways, subacute CS-exposure induced the expression of GCP-2, MCP-1, MIP-3alpha and resulted in a neutrophilic influx. However, after chronic CS-exposure, there was a significant downregulation of inflammation in the upper airways, while on the contrary, lower airway inflammation remained present. Whereas nasal FoxP3 mRNA levels already increased after 2 weeks, lung FoxP3 mRNA increased only after 4 weeks, suggesting that mechanisms to suppress inflammation occur earlier and are more efficient in nose than in lungs.Conclusions: Altogether, these data demonstrate that CS induced inflammation may be differently regulated in the upper versus lower airways in mice. Furthermore, these data may help to identify new therapeutic targets in this disease model. [ABSTRACT FROM AUTHOR]

Context: Recent insights into type 2 inflammation have led to the development of monoclonal antibody therapies for severe asthma and chronic rhinosinusitis with nasal polyps (CRSwNP). Despite add-on therapy with a monoclonal antibody, some individuals remain uncontrolled in terms of upper and/or lower airway symptoms, prompting an exploration of the efficacy of combining biological therapies and their impact on inflammatory pathways., Objectives: In this article, we present a distinctive case of a patient with CRSwNP, severe eosinophilic asthma, and uncontrolled upper airway symptoms, who experienced substantial clinical and local inflammatory improvements through dual monoclonal antibody therapy., Methods: We provide a detailed case description and analysis of the patient's nasal tissue and secretions to gain insights into the local nasal inflammation under this unique therapeutic approach., Results: The addition of an anti-IL-4Rα antibody led to an improvement in upper airway symptoms and a reduction in both eosinophilic and neutrophilic inflammation, despite prior anti-IL-5 therapy. These effects were consistently observed in both polyp tissue and nasal secretions., Conclusion: Our patient, with CRSwNP, severe eosinophilic asthma, and uncontrolled upper airway symptoms, experienced substantial improvement with dual monoclonal antibody therapy, without major complications or side effects., Competing Interests: GB has received fees for advisory boards and/or speaker fees from Amgen, AstraZeneca, Boehringer Ingelheim, Chiesi, GSK, Novartis, Sanofi, and Teva Pharmaceuticals. BNL received research support from GSK and Sanofi. PG has served as an advisor or speaker and received grant/research support from ALK, GSK, Lilly, Novartis, Regeneron, Roche, Sanofi, and Stallergenes-Greer. The remaining 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 Blauwblomme, Gevaert, Van Nevel, Riemann, Vandewalle, Holtappels, De Ruyck, Derycke, Eeckels, Vanhee, Lambrecht, Brusselle and Van Zele.)

Objective: The aim of this study was to evaluate the outcomes of cold stored saphenous vein allografts (CSVAs) for haemodialysis vascular access., Methods: A retrospective, two centre study was conducted between January 2016 and December 2020 of all patients who had CSVA placement for haemodialysis vascular access. Primary, primary assisted, and secondary patency were analysed, as well as procedural complications and re-interventions., Results: One hundred and nine patients (n = 55 women) with a mean age of 67.2 ± 13.6 years, with no options for creating an autogenous arteriovenous fistula, were included in the study. At one year, primary, primary assisted, and secondary patency were 37.6%, 59.0%, and 73.3%, respectively; and at two years 19.9%, 42.5%, and 54.9%, respectively. During a mean follow up period of 26 ± 18 months, five patients (4.6%) had an access infection, with no related death. During the follow up period, 32 patients (29.4%) died and 13 patients (11.9%) underwent a kidney transplant. None of these patients showed immunoconversion before transplantation. The cumulative incidence of adverse events by the Fine-Gray method was calculated. Considering competing risks (death and renal transplantation), 9.2% of patients lost their vascular access at one year and 18% at two years. Moreover, 57.8% patients had stenosis, mainly on the outflow (45.9%), and 49.5% had thrombosis., Conclusion: With a comparable patency rate associated with a low infection rate, CSVA offers a potential alternative to expanded polytetrafluoroethylene grafts. This creates haemodialysis vascular access when the venous capital is exhausted in patients with reported risk factors for vascular access infection, i.e., insertion in the thigh, advanced age, diabetes mellitus, immunocompromised state, obesity, or revision of an infected prosthetic graft., (Copyright © 2024 European Society for Vascular Surgery. Published by Elsevier B.V. All rights reserved.)

Current planning of aortic and peripheral endovascular procedures is based largely on manual measurements performed from the 3-dimensional reconstruction of preoperative computed tomography scans. Assessment of device behavior inside patient anatomy is often difficult, and available tools, such as 3-dimensional-printed models, have several limitations. Digital twin (DT) technology has been used successfully in automotive and aerospace industries and applied recently to endovascular aortic aneurysm repair. Artificial intelligence allows the treatment of large amounts of data, and its use in medicine is increasing rapidly. The aim of this review was to present the current status of DTs combined with artificial intelligence for planning endovascular procedures. Patient-specific DTs of the aorta are generated from preoperative computed tomography and integrate aorta mechanical properties using finite element analysis. The same methodology is used to generate 3-dimensional models of aortic stent-grafts and simulate their deployment. Post processing of DT models is then performed to generate multiple parameters related to stent-graft oversizing and apposition. Machine learning algorithms allow parameters to be computed into a synthetic index to predict Type 1A endoleak risk. Other planning and sizing applications include custom-made fenestrated and branched stent-grafts for complex aneurysms. DT technology is also being investigated for planning peripheral endovascular procedures, such as carotid artery stenting. DT provides detailed information on endovascular device behavior. Analysis of DT-derived parameters with machine learning algorithms may improve accuracy in predicting complications, such as Type 1A endoleaks., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: JN Albertini is co-founder of PrediSurge SAS., (Copyright © 2024 Elsevier Inc. All rights reserved.)

(1) Background: Endovascular abdominal aneurysm repair (EVAR) is associated with a reduction in early morbidity and mortality compared with open repair. Procedures performed under hypnosis might represent an alternative to further reduce the risks related to general anesthesia (GA). This study aimed to assess the feasibility and safety of hypnosis and local anesthesia during EVAR. (2) Methods: All consecutive patients who underwent EVAR or fenestrated/branched EVAR (f/bEVAR) under hypnosis and local anesthesia (n = 28) between 2017 and 2019 were retrospectively studied and matched to control patients who underwent the same interventions under GA. (3) Results: There was neither a significant difference in the length of ICU stay ( p = 0.06), nor in the occurrence of endoleaks, reintervention, and 30-day mortality rate ( p = 1.00, 0.73, and 0.24, respectively). The hypnosis group had lower use of norepinephrine (maximum dose 0.04 ± 0.1 vs. 1.2 ± 4.0 mg·h -1 , p < 0.001), shorter procedure duration (181.2 ± 71.4 vs. 214.3 ± 79.6 h, p = 0.04), and shorter length of stay (5.4 ± 3.2 vs. 8.4 ± 5.9 days, p = 0.002). (4) Conclusions: In this pioneering study, hypnosis during EVAR appears feasible and safe. It is associated with lower intraoperative use of norepinephrine, as well as procedure duration and length of in-hospital stay.

Objective: A proximal scallop design allows aortic arch repair without complex endovascular manipulation in the aortic arch. The aim was to assess the safety and efficacy at one year of the Relay proximal scallop stent graft., Methods: A prospective multicentre study evaluated consecutive patients treated with the Relay proximal scallop stent graft in 10 French aortic centres. All consecutive patients eligible for elective thoracic endovascular repair with proximal scallop in the 10 participating centres between January 2015 and July 2018 were included. Primary endpoints were 30 day mortality, stroke, and spinal cord ischaemia (SCI) rates. Outcomes including safety and efficacy, technical and clinical success, all cause death, neurological events, vessel patency, and device specific complications were analysed. Survival and survival without severe complications were estimated using Kaplan-Meier estimates., Results: Ten aortic centres treated 40 patients for thoracic aortic aneurysm (45%), penetrating atherosclerotic aneurysm (30%), and dissection (25%). Half of the procedures (50%) targeted zone 0 of the aortic arch (zone 0 in 17.5% and zones 0/1 in 32.5%), 37.5% targeted zone 2 (35% zone 2 alone; 2.5% zones 1/2), and 15% targeted zone 1 (12.5% zone 1 alone). Median follow up was one year. Thirty day mortality, stroke, and SCI rates were 10%, 5%, and 0% respectively. Primary technical success was 95%. Type Ia, Ib, and III endoleaks rates were 5.4%, 0%, and 0% respectively at one month. The overall mortality rate at one year was 17.5%. Aneurysm expansion was > 5 mm in one case at one year associated with type Ia endoleak (3%). There was no supra-aortic trunk thrombosis, one (2%) graft kink, and no migration., Conclusion: One year outcomes showed that the Relay proximal scallop stent graft is an acceptable answer to thoracic aortic disease to deal with short proximal landing zones., (Copyright © 2023 European Society for Vascular Surgery. Published by Elsevier B.V. All rights reserved.)

Purpose: To report biomarkers present in the olfactory mucosa in chronic rhinosinusitis with nasal polyps (CRSwNP) in comparison with nasal polyps and to nasal mucosal tissues from control patients. To evaluate the kinetics of smell over 6 months in patients who underwent Reboot surgery., Methods: Cohort study from May 2021 to May 2022. We collected samples of olfactory mucosa and nasal polyps from 16 CRSwNP patients and inferior turbinate samples from 20 control subjects. The study was not randomized for surgical and/or medical treatment. Samples were analyzed by Luminex and Unicap 100 to measure biomarkers of inflammation (IL1-β, IL4, IL5, IL6, IL17, CCL3, CCL4, G-CSF, SE-IgE, total IgE and ECP). 12 of the CRSwNP patients underwent Extended Sniffin'tests at timepoints 1-4 days pre-surgery, and 1, 3 and 6 months after Reboot surgery., Results: Type-2 markers were significantly elevated in OM and polyp tissue in CRSwNP (n = 16) vs. controls (n = 20), P < 0.05. TDI scores improved already 1 month (P < 0.05) after surgery and remained stable for 6 months. Type-2 inflammation in nasal polyps was associated with decreased sense of smell and taste before surgery, but improved after surgery (P = 0.048). Type-3 inflammation was present in the olfactory mucosa and was associated with a better sense of smell before surgery, but a smaller improvement of smell afterward., Conclusions: Type-2 inflammation is present in the olfactory mucosa in CRSwNP patients and is associated with smell loss. Reboot surgery, aiming to completely remove inflamed sinus mucosa, significantly improves the smell in this group of patients., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)