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Abstract Background Elderly asthmatics represent an important group that is often excluded from clinical studies. In this study we wanted to present characteristics of asthmatics older than 70 years old as compared to younger patients. Methods We conducted a retrospective analysis on a series of 758 asthmatics subdivided in three groups: lower than 40, between 40 and 70 and older than 70. All the patients who had a successful sputum induction were included in the study. Results Older patients had a higher Body Mass Index, had less active smokers and were more often treated with Long Acting anti-Muscarinic Agents. We found a significant increase in sputum neutrophil counts with ageing. There was no significant difference in blood inflammatory cell counts whatever the age group. Forced expiratory volume in one second (FEV1) and FEV1/FVC values were significantly lower in elderly who had lower bronchial hyperresponsiveness and signs of air trapping. We found a lower occurrence of the allergic component in advanced ages. Asthmatics older than 70 years old had later onset of the disease and a significant longer disease duration. Conclusion Our study highlights that asthmatics older than 70 years old have higher bronchial neutrophilic inflammation, a poorer lung function, signs of air trapping and lower airway variability. The role of immunosenescence inducing chronic low-grade inflammation in this asthma subtype remains to be elucidated.

Background: The study was designed to evaluate the clinical results of a composite material beta-tricalcium phosphate in combination with calcium sulphate in the treatment of periodontal intrabony defects. The combination of these materials is believed to aid in guieded tissue regeneration owing to their properties. Material and methods: A total of 47 teeth with intrabony defectsin in 26 periodontitis patiens were treated with Forthoss® Vital (Biocomposites, Staffordshiere, UK). Clinical parameters were evaluated included changes in probing depth, clinical attachement levels loss and gingival recession at the baseline and two years postoperatively. Results and conslusion: The mean in differences in mesurements between the baseline and two years postoperatively were a reduction of 2.07 ± 0.14 mm (p = 0.000) in case of probing depth and gain of 1.93 ± 1.36 mm (p = 0.000) in clinical attachement level; but an increase of 0.14 ± 0.73 mm (p = 0.571) in gingival recession. The study results showing that the treatment with the combination of beta-tricalcium phosphate and calcium phosphate and calcium sulphate led to a significantly favorable clinical improvement in periodontal intrabony defects two years after the surgery.

Aim of study: The study was focused on the decrease of the depth of periodontal pockets and to obtain the information about depth of pockets after this type of treatment. Another result was to have information if there are recessions of soft tissues and the grade of recessions. Also the attachement level was evaluated before and one year after treatment. Method: 21 patients were includuded to the study, all of them passed through inicial phase, collaboration was on very good level. Age between 21-53 yers. Set of patients was composed by eight men and 13 women. For further treatment of 39 teeth with pocket depth ≥ 5 mm after inicial therapy was recomended GTR. Recessions were measured before and after treatment. Also were registered values of BOP. X-ray pictures confirmed bone resorption. All patients were generaly healthy, last three months no medication by antibiotics or anticoagulation drugs. No women were pregnant. Teeth were vital or correctly endodontic treated. Results: The study confirmed decrease of the number of teeth with pockets in all measurements. Conspicious decrease of pocket depth was registered on aproximal sides it means mesialy and distaly. We registered more noteceable recession on vestibular sides.

Introduction: A review of newer drugs for topical or systemic administration useful in contemporary dentistry in the therapy of diseases of periodontal tissue, oral mucous membrane, and salivary glands available in Czech Republic was given in this article. Objectives: There were discussed mouthrinses containing chlorhexidine in lower concentrations and/or oxidation agents associated with reduced dark discoloration of teeth and lingual mucosa. FotoSan 630 represents a system for photodynamic antimicrobial therapy using monochromatic light produced by light-emitting diods for the photoinitiation of the toluidine blue O as a photosensitizer. It is declared for the supportive topical treatment of plaque-induced periodontopathies, periimplant defects, dry socket, infected root canals and caries lesions. Hyaluronic acid contained in commercial gel products Aloclair and Gengigel, lubricative product Aequasyal, and gel product SineHerp are recommended in topical treatment of various less serious diseases of the oral mucosa and salivary glands. Drugs for systemic administration discussed here are antileukotriene immunomodulator montelucast, immunosuppressive and antiinflammatory drugs thalidomide and leflunomid. They are usable in the therapy of more serious mucosal diseases, mostly of autoimmune or uncertain origin. Caspofungin, micafungin and anidulafungin are modern echinocandin antimycotics for parenteral use indicated for treatment of severe mycotic infections, mostly candidiasis in altered individuals. Drugs for biological therapy declared as antitumorous and antiinflammatory agents already seldom used in dentistry are monoclonal antibodies rituximab, cetuximab, and erlotinib, potentially useful are also etanercept, infliximab and adalimumab. Botulotoxin is a neurotoxin of bacterial origin used at present in the therapy of various neurological disturbances in the head and neck area.

Introduction: There are many of drugs useful for topical or systemic treatment of diseases of periodontal tissue and oral mucous membrane. Their correct administration and efficacy depend strictly on adeqnate of information regarding their properties. Aim: The review deals with some drugs newly available in Czech Republic and related therapeutic procedures used in the treatment of periodontal and mucosal diseases. Therapeutic agents: For topical chemical inhibition of the dental plaque are dedicated octenidine, kationic antiseptic pyridine derivate, and combination of classic bis-biguanide derivate chlorhexidine with aromatic agent eugenol. As adjuvant chemotherapeutics in the treatment of periodontitis serve systems for targeted antimicrobial photodynamic therapy based on the use of photosensitizers as producers of the singlet oxygen, namely toluidine blue O and methylen blue. The source of monochromatic light for their pohotoactivation is laser device. Saturated alcohol docosanol with antiviral acitivity serves in topical therapy of labial herpes. Vanillinamide alkaloid capsaicine is selective agonist of vanilloid receptore TRPV 1 of sensitive nerves. Patch product Qutenza has been recently used for higly effective topical treatment of neuropatic pain. It could be potentially very useful agent in the treatment of some forms of atypical facial pain. Irradiation of salivary glands results in association with its dosis in the damage of various grade of the glandular parenchyma associated with postirradiative hyposialia. Cytoprotective prodrug amifostine releases active thiol after its dephosphorylation. It is recommended for the protection of the glandular parenchyma against adverse effects of antitumorous drugs and therapeutic irradiation in the region of the head and neck. Conclusion: Spectrum of therapeutic agents useful in the treatment of periodontal and mucosal diseases raises permanently. Efficacy of their application is connected with sufficient information of professionals and correct and early diagnosis of the disease, as well.

Oral lichen planus (OLP) and recurrent aphtous stomatitis are the most frequent diseases of oral mucosa. Epidemiologic studies are demonstrating the frequency of 1-2 % in adult population. OLP is very frequently discussed in scientific literature. However, the etiology remains still unclear. Pathogenetic processes of OLP are partly elucidated. Changes involving the region of basal membrane are suggested to be the result of the apoptosis of keratinocytes. Apoptosis of keratinocytes is caused by CD8+Tlymphocytes. These cells are activated by TNFα. After the death of keratinocytes the stability of the basal membrane is changed, the basal membrane is splitted (teared). MMP 9 is involved in enhacing the process. Actually it is impossible to explore this knowledge in the treatment of OLP because the initial factor of the pathogenetic process is unknown.

Background: Asthma is associated with accelerated rate of FEV 1 decline., Objective: To determine predictive factors associated with accelerated FEV 1 decline in adult asthma and evaluate sputum cytokines as potential biomarkers for airflow decline., Methods: We recruited 125 asthmatics evaluated at the asthma clinic of Liège and reevaluated them at least 5 years later. Clinical, functional and inflammatory characteristics were compared between patients with accelerated decline (FEV 1 decline > 0.85% pred.y -1 ) and others. Predictive factors were highlighted with linear regression analysis. Sputum EGF, VEGF, FGF, IL5, IL8, TGF-β, and IgE levels were measured in 58 of these patients at both visits by Human XL cytokine Luminex Performance assay and Elisa., Results: Post-BD FEV 1 decline was 0.06 ± 2.44% pred.y -1 in the overall population. Median (IQR) time between visits was 66 (62 - 86) months. The multivariable analysis showed that an increase in blood eosinophils over time (Δ BEC) (Reg. Coef. (95%CI): 0.002 (0.001 to 0.004), p = 0.005)) and onset of asthma (0.04 (0.003 to 0.07), p = 0.036) were independently associated with FEV 1 decline. IL8 levels measured at baseline were higher (499 (408-603) pg/ml, p = 0.0040) in patients with accelerated decline compared to others (143 (88-308) pg/ml)., Conclusion: In this study, we have confirmed that an increase in blood eosinophil counts over a follow-up of at least 5 years and later onset of asthma are associated with accelerated annual FEV 1 decline. Moreover, high sputum IL8 levels could be a risk factor for accelerated decline in asthma patients., Competing Interests: Declarations. Conflict of interests: Graff S, Moermans C, Gerday S, Henket M, Paulus P, and Guissard F have nothing to disclose. Prof. LOUIS reports grants and personal fees from GSK, grants and personal fees from AZ, grants and personal fees from Novartis, grants from Chiesi, outside the submitted work. Prof. Schleich reports grants and personal fees from GSK, grants from AZ, grants and personal fees from Chiesi, outside the submitted work. Ethical Approval: CHU Liège: 2008/181. Informed Consent: Informed consent was obtained from all individual participants included in the study. Consent for Publication: Not applicable., (© 2024. The Author(s).)

Decarbonization of energy production is key in today's societies and nuclear energy holds an essential place in this prospect. Besides heavy-duty electricity production, other industrial and communal needs could be served by integrating novel nuclear energy production systems, among which are low-power nuclear devices, like small modular reactors (SMRs). The ELSMOR (towards European Licensing of Small Modular Reactors) European project addresses this topic as an answer to the Horizon 2020 Euratom NFRP-2018-3 call. The consortium includes 15 partners from eight European countries, involving research institutes, major European nuclear companies and technical support organizations. The 3.5-year project, launched in September 2019, investigates selected safety features of light-water (LW) SMRs with focus on licensing aspects. Providing a comprehensive compliance framework that regulators can adopt and operate, the licensing process of such SMRs could be optimized, helping their deployment. In this prospect, as a result of ELSMOR's work, this article gives an overview of the specific issues that LW-SMRs may bring about in the different domains of nuclear safety, in terms of: •Methodological standpoints: safety goals, safety requirements, safety principles (defence-in-depth implementation);•Main safety functions of reactivity control, decay heat removal and confinement management;•Severe accident management;•Other safety issues particular to SMRs: use of shared systems; performing of multi-unit probabilistic safety assessment (PSA); spent fuel management, transport and disposal management. In this article, adequate methodologies are developed to deal with these issues and to help assess the safety of LW-SMRs. This work gives a precious synthesis of the safety assessment issues of LW-SMRs and of the associated methodologies developed in the context of the ELSMOR European project., Competing Interests: No competing interests were disclosed., (Copyright: © 2024 Lansou S et al.)

Background: Although asthma is often seen as an eosinophilic disease associated with atopy, patients with noneosinophilic asthma represent a substantial part of the population with asthma., Objective: To apply an unsupervised clustering method in a cohort of 588 patients with noneosinophilic asthma (sputum eosinophils < 3%) recruited from an asthma clinic of a secondary care center., Methods: Our cluster analysis of the whole cohort identified 2 subgroups as cluster 1 (n = 417) and cluster 2 (n = 171)., Results: Cluster 1 comprised a predominantly female group with late disease onset, a low proportion of atopy (24%), and a substantial smoking history (53%). In this cluster, treatment burden was low (<50% of inhaled corticosteroid users); asthma control and quality of life were poor, with median Asthma Control Test, Asthma Control Questionnaire, and Asthma Quality of Life scores of 16, 1.7, and 4.5, respectively, whereas lung function was preserved with a median postbronchodilation forced expiratory volume in 1 second of 93% predicted. Cluster 2 was a predominantly male group, almost exclusively comprising patients with atopy (99%) with early disease onset and a moderate treatment burden (median inhaled corticosteroids dose 800 µg/d equivalent beclomethasone). In cluster 2, asthma was partially controlled, with median Asthma Control Test and Asthma Control Questionnaire scores reaching 18 and 1.3, respectively, and lung function well preserved with a median postbronchodilation of 95% predicted. Although systemic and airway neutrophilic inflammation was the dominant pattern in cluster 1, cluster 2 essentially comprised paucigranulocytic asthma with moderately elevated fraction exhaled nitric oxide., Conclusion: Noneosinophilic asthma splits into 2 clusters distinguishing by disease onset, atopic status, smoking history, systemic and airway inflammation, and disease control and quality of life., Competing Interests: Disclosures Dr Louis reports an educational grant and lecture fees from GlaxoSmithKline, a research grant and advisory board fees from AZ, a research grant from Chiesi, and a research grant and advisory board fees from Novartis, outside the submitted work. Dr Schleich reports lecture and advisory board fees from GlaxoSmithKline, AZ, Chiesi, and Novartis outside of the submitted work., (Copyright © 2024 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Randomised controlled trials have shown that benralizumab, an anti-interleukin-5 receptor monoclonal antibody, reduces exacerbations and oral corticosteroid dose and improves asthma control and lung function in severe eosinophilic asthma. The aim of this study was to confirm results of randomised controlled trials in real life in a population of 73 patients with severe eosinophilic asthma treated with benralizumab for at least 12 months., Methods: Patients underwent careful monitoring of asthma exacerbations, exhaled nitric oxide fraction, lung function, asthma control and quality of life questionnaire responses and sputum induction, and gave a blood sample at baseline, after 6 months and then every year., Results: We found significant reductions in exacerbations (by 92%, p<0.0001) and oral corticosteroid dose (by 83%, p<0.001) after 6 months that were maintained over time, with 78% of patients able to stop oral corticosteroid therapy. Patients improved their Asthma Control Test (ACT) score (from 11.7±5.1 to 16.9±5.35, p<0.0001), Asthma Control Questionnaire (ACQ) score (from 2.88±1.26 to 1.77±1.32, p<0.0001) and Asthma Quality of Life Questionnaire score (+1.04, p<0.0001) at 6 months and this was maintained during follow-up. Only 35% and 43% of patients reached asthma control according to an ACT score ≥20 and ACQ score <1.5, respectively. We observed stable post-bronchodilation lung function over time and a significant reduction in sputum eosinophil count, with 85% of patients exhibiting sputum eosinophil counts <3% after 6 months (p<0.01) with no effect on exhaled nitric oxide fraction., Conclusion: In our real-life study, we confirm the results published in randomised controlled trials showing a sharp reduction in exacerbations and oral corticosteroid therapy, an improvement in asthma control and quality of life, and a dramatic reduction in sputum eosinophil count., Competing Interests: Conflict of interest: F. Schleich reports grants or contracts from GSK, AstraZeneca, Chiesi and Novartis, outside the submitted work; consulting fees from GSK, AstraZeneca, Chiesi and Novartis, outside the submitted work; and lectures for GSK, AstraZeneca, Chiesi and Novartis, outside the submitted work. Conflict of interest: A-L. Poirrier reports a speaker honorarium from GlaxoSmithKline Pharmaceuticals SA outside the submitted work; and advisory board honoraria from GlaxoSmithKline Pharmaceuticals SA and Sanofi Aventis Belgium SA, outside the submitted work. Conflict of interest: R. Louis reports grants or contracts from GSK, AstraZeneca and Chiesi, outside the submitted work; payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing or educational events from GSK, AstraZeneca, Chiesi and TEVA, outside the submitted work; and participation on a data safety monitoring or advisory board for GSK and AstraZeneca, outside the submitted work. Conflict of interest: The remaining authors have nothing to disclose., (Copyright ©The authors 2023.)

Several clinical trials have demonstrated that anti-IL-5(R) biologics were able to improve lung function, asthma control and chronic oral corticosteroid exposure and reduce exacerbations among eosinophilic asthmatic patients. However, a certain variability in clinical responses to anti-IL-5(R) biologics was brought to light. Our study aimed at evaluating the role of baseline sputum eosinophils in identifying super-responders to mepolizumab and benralizumab. Our study reinforces the importance to examine sputum eosinophils in patients suffering from severe asthma before starting a biologic as it is associated with the intensity of response to mepolizumab and benralizumab., Competing Interests: Competing interests: GERDAY Sara, GRAFF Sophie, MOERMANS Catherine, GUISSARD Françoise, PAULUS Virginie and HENKET Monique declare no competing interests. LOUIS Renaud reports grants from GSK, Astrazeneca, Chiesi; royalties from patent AU2016328384, CA2997506, EP 3337393, US2020345266; consulting fees from Astrazeneca; lecture payments from GSK, Chiesi; participation on a data safety monitoring board or advisory board for Astrazeneca ANDHI in practice study and leadership or fiduciary role in other board, society, committee or advocacy group for ERS task force on guidelines on asthma diagnosis, outside the submitted work. SCHLEICH Florence reports grants from GSK, Astrazeneca, Chiesi; consulting fees from GSK, Astrazeneca, Sanofi; lecture payments from GSK, Astrazeneca, Teva, Chiesi and Amgen and support for attending meetings/travel from Chiesi, outside the submitted work., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Staphylococcus aureus enterotoxins (SE) may act as superantigens and induce an intense T-cell activation, causing local production of polyclonal IgE and resultant eosinophil activation., Objective: To assess whether asthma with sensitization to SE but not to common aeroallergens (AAs) displays different inflammatory characteristics., Methods: We conducted a prospective study on a series of 110 consecutive patients with asthma recruited from the University Asthma Clinic of Liège. We compared clinical, functional, and inflammatory characteristics of this general population of patients with asthma categorized into 4 groups according to sensitization to AAs and/or SE. We also compared sputum supernatant cytokines in patients sensitized to SE or not., Results: Patients with asthma sensitized only to AAs represented 30%, while 29% were sensitized to both AAs and SE. One-fifth of the population had no specific IgE. Sensitization to SE but not to AA (21%) was associated with later onset of disease, higher rate of exacerbations, nasal polyps, and more severe airway obstruction. As for airway type 2 biomarkers, patients presenting with specific IgE against SE displayed higher fractional exhaled nitric oxide, sputum IgE, and sputum IL-5 levels but not IL-4. We confirm that the presence of specific IgE against SE is associated with elevated serum IgE to levels well above those observed in patients sensitized only to AAs., Conclusions: Our study suggests that asthma specialists should measure specific IgE against SE during the phenotyping process because it may allow the identification of a subgroup of patients with more asthma exacerbations, more nasal polyposis and chronic sinusitis, lower lung function, and more intense type 2 inflammation., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: Asthma negatively impacts health-related quality of life (HRQL). The objective is to investigate the longitudinal relationship between HRQL in asthma and disease control, demographic and clinical objective parameters in an adult population in real-life settings., Methods: We conducted a longitudinal study on adult asthmatics recruited from Liege University Hospital Asthma Clinic (Belgium) between 2011 and 2019. We selected those who had two visits and completed two patient-reported outcome measures (PROMs), the asthma control test (ACT) and the mini asthma quality of life questionnaire (AQLQ) (n = 290). AQLQ was the dependent variable. Demographic, functional and inflammatory characteristics, asthma control, and exacerbations were the independent variables. We applied generalized linear mixed models to identify the factors associated with change in AQLQ and its dimensions., Results: Median (IQR) time interval between the two visits was 7 (5-19) months. Overall, median (IQR) global AQLQ increased from 4.1 (3-5.1) to 4.6 (3.4-5.9) (p < 0.0001). All AQLQ dimensions significantly improved, apart the environmental one. AQLQ improved in patients who had both step-up and step-down pharmacological treatment as well as in patients reporting no change between the two visits. The fitted models indicated that change in ACT was the main predictor of change in AQLQ (p < 0.0001). A rise in 3 units in ACT predicted an improvement of 0.5 AQLQ (AUC-ROC = 0.85; p < 0.0001). Change in BMI inversely impacted global AQLQ (p < 0.01) and its activity dimension (p < 0.0001)., Conclusion: Asthma control and BMI are key predictors of asthma quality of life acting in an opposite direction. AQLQ may improve without step-up in the pharmacological treatment., (© 2023. The Author(s).)

Introduction: Although asthma is a common disease, its diagnosis remains a challenge in clinical practice with both over- and underdiagnosis. Here, we performed a prospective observational study investigating the value of symptom intensity scales alone or combined with spirometry and exhaled nitric oxide fraction ( F ENO ) to aid in asthma diagnosis., Methods: Over a 38-month period we recruited 303 untreated patients complaining of symptoms suggestive of asthma (wheezing, dyspnoea, cough, sputum production and chest tightness). The whole cohort was split into a training cohort (n=166) for patients recruited during odd months and a validation cohort (n=137) for patients recruited during even months. Asthma was diagnosed either by a positive reversibility test (≥12% and ≥200 mL in forced expiratory volume in 1 s (FEV 1 )) and/or a positive bronchial challenge test (provocative concentration of methacholine causing a 20% fall in FEV 1 ≤8 mg·mL -1 ). In order to assess the diagnostic performance of symptoms, spirometric indices and F ENO , we performed receiver operating characteristic curve analysis and multivariable logistic regression to identify the independent factors associated with asthma in the training cohort. Then, the derived predictive models were applied to the validation cohort., Results: 63% of patients in the derivation cohort and 58% of patients in the validation cohort were diagnosed as being asthmatic. After logistic regression, wheezing was the only symptom to be significantly associated with asthma. Similarly, FEV 1 (% pred), FEV 1 /forced vital capacity (%) and F ENO were significantly associated with asthma. A predictive model combining these four parameters yielded an area under the curve of 0.76 (95% CI 0.66-0.84) in the training cohort and 0.73 (95% CI 0.65-0.82) when applied to the validation cohort., Conclusion: Combining a wheezing intensity scale with spirometry and F ENO may help in improving asthma diagnosis accuracy in clinical practice., Competing Interests: Conflict of interest: Outside of this submitted work, R. Louis received unrestricted research grants from GSK, AstraZeneca and Chiesi, and lecture or advisory board fees from GSK, AstraZeneca, Novartis and Sanofi. Outside of this submitted work, F. Schleich received lecture or advisory board fees from Chiesi, AstraZeneca, GSK and Novartis. The rest of the authors declare that they have no relevant conflicts of interest., (Copyright ©The authors 2023.)

Introduction: The coronavirus Severe Acute Respiratory Syndrome Coronavirus Type 1 induces a severe respiratory disease, coronavirus disease 2019 (COVID-19). After Severe Acute Respiratory Syndrome Coronavirus Type 1 and Middle East Respiratory Syndrome infection, increased post-traumatic stress disorder (PTSD) rates were described., Methods: This single-centred, prospective study aimed to evaluate the rates of PTSD in patients who were hospitalized for COVID-19. Inclusion criteria were COVID-19 patients hospitalized in the intensive care unit (ICU) or in a standard unit with at least 2 L/min oxygen. Six months post-hospitalization, subjects were assessed for PTSD using a validated screening tool, the Post-Traumatic Stress Checklist-5 (PCL-5)., Results: A total of 40 patients were included. No demographic differences between the ICU and non-ICU groups were found. The mean PCL-5 score for the population was 8.85±10. The mean PCL-5 score was 6.7±8 in the ICU group and 10.5±11 in the non-ICU group (P=0.27). We screened one patient with a positive PCL-5 score and one with a possible PCL-5 cluster score. Nine patients had a PCL-5 score of up to 15. Seven patients reported no symptoms. Seven patients accepted a psychological follow-up: one for PTSD, three for possible PTSD and three for other psychological problems., Discussion: The PCL-5 tool can be used by lung physicians during consultations to identify patients for whom follow-up mental health assessment and treatment for PTSD are warranted., Conclusion: Lung physicians should be aware of the risk of PTSD in patients hospitalized for COVID-19 and ensure appropriate screening and follow-up care., Competing Interests: The authors have no conflicts of interest to declare.

Introduction: Cannabidiol (CBD) is a phytocannabinoid found in the Cannabis plant. CBD has received significant medical attention in relation to its anticonvulsant, anxiolytic, and antipsychotic characteristics. An increasing number of studies focusing on the anti-addictive properties of CBD have recently been published. In this systematic review, we aim to offer a comprehensive overview of animal and human studies regarding the impact of CBD on substance use disorders (SUDs)., Methods: A systematic search was performed on the PubMed database in February 2021. We included all articles assessing the effects of CBD on substance use disorders., Results: The current systematic review suggests that CBD might offer promising therapeutic potential for the treatment of SUD, based on available animal and human studies. Animal studies showed a positive impact of CBD in the context of alcohol, opioids, and methamphetamine use (e.g., diminishing of drug-seeking behaviors). The results for cocaine use were mixed among reviewed studies, and CBD was not found to have an effect in animal studies on cannabis use. No animal study was identified that focused on the impact of CBD on nicotine use. Human studies showed a positive impact of CBD in the context of nicotine, cannabis, and opioid use (e.g., frequency and quantity of consumption). In contrast, CBD was not found to have an effect in human studies on cocaine or alcohol use. No human study was identified that investigated the impact of CBD on methamphetamine use., Conclusions: CBD might offer promising therapeutic potential for the treatment of SUD, especially for nicotine, cannabis, and opioid use disorders, based on available human studies. The available research evidence is, however, sparse and more research on humans is needed., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Macroautophagy promotes cellular homeostasis by delivering cytoplasmic constituents to lysosomes for degradation [Mizushima, Nat. Cell Biol. 20, 521-527 (2018)]. However, while most studies have focused on the mechanisms of protein degradation during this process, we report here that macroautophagy also depends on glycan degradation via the glycosidase, α-l-fucosidase 1 (FUCA1), which removes fucose from glycans. We show that cells lacking FUCA1 accumulate lysosomal glycans, which is associated with impaired autophagic flux. Moreover, in a mouse model of fucosidosis-a disease characterized by inactivating mutations in FUCA1 [Stepien et al. , Genes (Basel) 11, E1383 (2020)]-glycan and autophagosome/autolysosome accumulation accompanies tissue destruction. Mechanistically, using lectin capture and mass spectrometry, we identified several lysosomal enzymes with altered fucosylation in FUCA1-null cells. Moreover, we show that the activity of some of these enzymes in the absence of FUCA1 can no longer be induced upon autophagy stimulation, causing retardation of autophagic flux, which involves impaired autophagosome-lysosome fusion. These findings therefore show that dysregulated glycan degradation leads to defective autophagy, which is likely a contributing factor in the etiology of fucosidosis.

Background: Atopic asthma is one of the most common asthma phenotypes and is generally opposed to the non-atopic counterpart. There have been very few large-scale studies comparing atopic and non-atopic asthmatics in terms of systemic and airway inflammation across the age spectrum., Methods: Here, we have undertaken a retrospective study investigating 1626 patients (924 atopic and 702 non-atopic asthmatics) recruited from our university asthma clinic who underwent extensive clinical investigations including induced sputum. Atopy was defined by any positive specific IgE to common aeroallergens (>0,35 kU/L). We performed direct comparisons between the groups and sought to appreciate the influence of age on the airway and systemic inflammatory components. The study was approved by the ethics committee of the University Hospital of Liege (Ref. 2016/276). Informed consents were obtained from healthy subjects., Results: Atopic asthmatics were younger (P  < .001), had a higher male/female ratio (P  < .001), an earlier disease onset (P  < .001) and a greater proportion of treated rhinitis (P  < .001) while non-atopic asthmatics had greater smoke exposure (P  < .001), lower FEV 1 /FVC ratio ( P  = .01) and diffusing capacity ( P  < .001). There was no difference between the 2 groups regarding FEV 1 (% predicted), asthma control, asthma quality of life and exacerbations in the previous 12 months. Regarding inflammation, atopic patients had higher FeNO levels (median = 28 ppb, P  < .001), were more eosinophilic both in blood (median = 2.8%, P  < .001) and in sputum (median = 2.2%, P  < .001) while non-atopic patients displayed greater blood (median = 57%, P  = .01) and sputum (median = 58.8%, P  = .01) neutrophilic inflammation. However, stratifying patients by age showed that non-atopic asthmatics above 50 years old became equally eosinophilic in the sputum (P  = .07), but not in the blood, as compared to atopic patients. Likewise, FeNO rose in non-atopic patients after 50 years old but remained, however, lower than in atopic patients., Conclusions: We conclude that, while sharing many features, atopic group still differentiates from non-atopic asthmatics by demographics, functional and inflammatory profiles. When atopic asthmatics showed a constant eosinophilic pattern across the age spectrum, non-atopic asthmatics were found to be neutrophilic before the age of 50 but eosinophilic above 50 years old., Competing Interests: SG, FG, VP, MH: no competing interests. FS reports grants from GSK, Astrazeneca, Teva, Chiesi and Novartis; consulting fees from GSK, Astrazeneca, Amgen, Chiesi and Novartis; lecture payments from GSK, Astrazeneca, Teva, Chiesi and Novartis, outside the submitted work. RL reports grants from GSK, AZ, Novartis, Chiesi and Teva; royalties from patent AU2016328384, CA2997506, EP 3337393, US2020345266; consulting fees and lecture payments from GSK, AZ, Novartis, Sanofi and Chiesi, outside the submitted work., (© 2022 The Authors.)

Asthma is a chronic inflammatory disease of the airways. Classification of asthma in different phenotypes has therapeutic implications and may lead to personalized medicine. Induced sputum is the gold standard for asthma phenotyping but is complex, time-consuming and not widely available. The combination of different biomarkers such as exhaled nitric oxide, blood eosinophils and total serum IgE levels allows the prediction of inflammatory phenotype in 58% of asthmatic patients when sputum is not available. We recently demonstrated the interest of measuring volatile organic compounds in exhaled breath to phenotype asthma. These compounds could play an important role in the future to predict the response to expensive biologicals available in severe asthma to reduce exacerbations and the use of systemic corticosteroids.

Background: Vascularized lymph node transfer (VLNT) has become an increasingly popular technique for treating lymphedema. However, although many studies have been performed, its efficacy in increasing patients' quality of life (QoL) and reducing lymphedema in the affected body part has remained controversial. In the present systematic review, we summarized the evidence for VLNT for treating breast cancer-related lymphedema., Methods: The MEDLINE, Embase, and Cochrane Central databases were searched for studies of patients with breast cancer-related lymphedema who had received VLNT. The study methods were assessed using the MINORS (methodologic index for nonrandomized studies) tool. The primary outcomes were the change in volume difference between the arms and QoL. The secondary outcomes were skin infection, complications, and discontinuation of compression garment use., Results: A total of 17 studies were included for qualitative synthesis and 8 for meta-analysis. The average reduction rate between the healthy and affected arms in the studies included in the meta-analysis was 40.31%. Five studies had evaluated QoL, and all five studies had reported that QoL was significantly increased. Eight studies had evaluated skin infections, of which three had reported the annual infection rates before and after surgery. In these studies, infection rate had decreased significantly. Three studies had described usage of compression garments. When the patients were pooled, 27 of 60 were able to discontinue use of the compression garment. The donor and recipient complication rates were 12.1% and 7.3%, respectively., Conclusions: The current evidence indicates that VLNT can improve the volume differences between the arms in patients with unilateral lymphedema by ∼40%. In addition, although determined from a few studies, it is likely that VLNT has a positive effect on patients' QoL, the number of skin infections, and compression garment usage and coincided with a low complication rate., (Copyright © 2021 The Author. Published by Elsevier Inc. All rights reserved.)

Fibroblasts display extensive transcriptional heterogeneity, yet functional annotation and characterization of their heterocellular relationships remains incomplete. Using mass cytometry, we chart the stromal composition of 18 murine tissues and 5 spontaneous tumor models, with an emphasis on mesenchymal phenotypes. This analysis reveals extensive stromal heterogeneity across tissues and tumors, and identifies coordinated relationships between mesenchymal and immune cell subsets in pancreatic ductal adenocarcinoma. Expression of CD105 demarks two stable and functionally distinct pancreatic fibroblast lineages, which are also identified in murine and human healthy tissues and tumors. Whereas CD105-positive pancreatic fibroblasts are permissive for tumor growth in vivo, CD105-negative fibroblasts are highly tumor suppressive. This restrictive effect is entirely dependent on functional adaptive immunity. Collectively, these results reveal two functionally distinct pancreatic fibroblast lineages and highlight the importance of mesenchymal and immune cell interactions in restricting tumor growth., Competing Interests: Declaration of interests O.S. receives funding from Novartis, AstraZeneca, RedEx and Cancer Research Technology. C.J. receives funding from AstraZeneca. R.M. is an expert witness for Pfizer and, as a former employee of the Institute of Cancer Research (ICR) in London, may benefit financially from commercialized programs. C.S. and F.L. are former employees of the ICR in London and may benefit financially from commercialized programs. The other authors declare no competing interests., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)