ISSN 0253-2778

CN 34-1054/N

Open AccessOpen Access JUSTC Life Sciences 01 April 2024

Association between active and passive smoking and the clinical course of multiple sclerosis and neuromyelitis optica spectrum disorder

Cite this:
https://doi.org/10.52396/JUSTC-2023-0004
More Information
  • Author Bio:

    Fengling Qu is currently a master’s student in the Department of Life Sciences and Medicine, University of Science and Technology of China, under the supervision of Prof. Xinfeng Liu. Her research mainly focuses on relapse and progression of demyelinating diseases

    Chunrong Tao is currently an Attending Physician in the Department of Neurology, the First Affiliated Hospital of USTC. He received his Ph.D. degree in Neurology from the University of Science and Technology of China in 2019. His research mainly focuses on epidemiology

    Wei Hu is currently a Chief Physician in the Department of Neurology, the First Affiliated Hospital of USTC. He received his Ph.D. degree in Neurology from Anhui Medical University in 2017. His research mainly focuses on the pathogenesis of cerebral collateral circulation and ischemic stroke

    Xinfeng Liu is currently a Professor in the Department of Life Sciences and Medicine, University of Science and Technology of China. He received his Ph.D. degree in Neurology from the University of Lausanne, Switzerland, in 2001. His research mainly focuses on interventional diagnosis and treatment of cerebrovascular diseases

  • Corresponding author: E-mail: 601893613@qq.com; E-mail: andinghu@ustc.edu.cn; E-mail: xfliu2@ustc.edu.cn
  • Received Date: 12 January 2023
  • Accepted Date: 10 May 2023
  • Available Online: 01 April 2024
  • Objective: Active and passive smoking are common environmental risk factors, but there is no definite conclusion about their effects on relapse and disability progression in multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD). Methods: This was a retrospective cohort study. Patients were included from four centers. Demographic and clinical data were extracted from the clinical database, while data involving environmental exposures during daily life, relapse, and disability progression were obtained through telephone follow-up interviews. Determinants of relapse were assessed by Cox proportional models, and disability progression was assessed by linear regression. Kaplan‒Meier survival was used to estimate relapse within five years after the first attack. Results: A total of 130 MS patients and 318 NMOSD patients were included in this study, and females accounted for 60% and 79.6%, respectively. MS patients with an active smoking history had a higher risk of relapse, for which the association became borderline significant after accounting for covariates (aHR=1.52, 95% CI=1.00, 2.31; p=0.052). The relapse risk between ever-smokers who smoked more than 10 cigarettes per day and smokers who smoked less than 10 cigarettes per day was not significantly different (aHR=0.96, 95% CI=0.63, 1.47; p=0.859). However, exposure to passive smoking was associated with a reduced risk of MS relapse (aHR=0.75, 95% CI=0.56, 1.00; p=0.044) compared with never-exposed patients. No associations were observed between active smoking/passive smoking and the risk of NMOSD relapse, but patients with a history of smoking were associated with a lower annual progression rate by Expanded Disability Status Scale (EDSS) (aβ=−0.20, 95% CI=−0.38, −0.01; p=0.036) and Multiple Sclerosis Severity Score (MSSS) (aβ=−0.23, 95% CI=−0.44, −0.03; p=0.028). Conclusion: Our research shows that active smoking increases the relapse risk of MS and has a negative impact on disability progression; thus, smoking cessation should be encouraged.
    The mechanism of cigarette smoke affecting demyelinating diseases.
    Objective: Active and passive smoking are common environmental risk factors, but there is no definite conclusion about their effects on relapse and disability progression in multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD). Methods: This was a retrospective cohort study. Patients were included from four centers. Demographic and clinical data were extracted from the clinical database, while data involving environmental exposures during daily life, relapse, and disability progression were obtained through telephone follow-up interviews. Determinants of relapse were assessed by Cox proportional models, and disability progression was assessed by linear regression. Kaplan‒Meier survival was used to estimate relapse within five years after the first attack. Results: A total of 130 MS patients and 318 NMOSD patients were included in this study, and females accounted for 60% and 79.6%, respectively. MS patients with an active smoking history had a higher risk of relapse, for which the association became borderline significant after accounting for covariates (aHR=1.52, 95% CI=1.00, 2.31; p=0.052). The relapse risk between ever-smokers who smoked more than 10 cigarettes per day and smokers who smoked less than 10 cigarettes per day was not significantly different (aHR=0.96, 95% CI=0.63, 1.47; p=0.859). However, exposure to passive smoking was associated with a reduced risk of MS relapse (aHR=0.75, 95% CI=0.56, 1.00; p=0.044) compared with never-exposed patients. No associations were observed between active smoking/passive smoking and the risk of NMOSD relapse, but patients with a history of smoking were associated with a lower annual progression rate by Expanded Disability Status Scale (EDSS) (aβ=−0.20, 95% CI=−0.38, −0.01; p=0.036) and Multiple Sclerosis Severity Score (MSSS) (aβ=−0.23, 95% CI=−0.44, −0.03; p=0.028). Conclusion: Our research shows that active smoking increases the relapse risk of MS and has a negative impact on disability progression; thus, smoking cessation should be encouraged.
    • We evaluated the impact of passive smoking on multiple sclerosis (MS) relapse and disability progression.
    • Compared to never-smokers, patients with MS who actively smoke have a significantly increased risk of relapse.
    • In MS, compared to never-smokers, active smokers experience accelerated disability progression.

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    Höftberger R, Lassmann H. Inflammatory demyelinating diseases of the central nervous system. Handb. Clin. Neurol., 2017, 145: 263–283. doi: 10.1016/B978-0-12-802395-2.00019-5
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    Lennon V A, Wingerchuk D M, Kryzer T J, et al. A serum autoantibody marker of neuromyelitis optica: distinction from multiple sclerosis. Lancet, 2004, 364 (9451): 2106–2112. doi: 10.1016/S0140-6736(04)17551-X
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    [4]
    Rosso M, Chitnis T. Association between cigarette smoking and multiple sclerosis: A review. JAMA Neurol., 2020, 77 (2): 245–253. doi: 10.1001/jamaneurol.2019.4271
    [5]
    Messina S, Mariano R, Geraldes R, et al. The influence of smoking on the pattern of disability and relapse risk in AQP4-positive Neuromyelitis Optica Spectrum Disorder, MOG-Ab Disease and Multiple Sclerosis. Mult. Scler. Relat. Disord., 2021, 49: 102773. doi: 10.1016/j.msard.2021.102773
    [6]
    Lavery A M, Collins B N, Waldman A T, et al. The contribution of secondhand tobacco smoke exposure to pediatric multiple sclerosis risk. Mult. Scler., 2019, 25 (4): 515–522. doi: 10.1177/1352458518757089
    [7]
    Pittas F, Ponsonby A L, van der Mei I A F, et al. Smoking is associated with progressive disease course and increased progression in clinical disability in a prospective cohort of people with multiple sclerosis. J. Neurol., 2009, 256 (4): 577–585. doi: 10.1007/s00415-009-0120-2
    [8]
    Petersen E R, Oturai A B, Koch-Henriksen N, et al. Smoking affects the interferon beta treatment response in multiple sclerosis. Neurology, 2018, 90 (7): e593–e600. doi: 10.1212/WNL.0000000000004949
    [9]
    Munger K L, Fitzgerald K C, Freedman M S, et al. No association of multiple sclerosis activity and progression with EBV or tobacco use in BENEFIT. Neurology, 2015, 85 (19): 1694–1701. doi: 10.1212/WNL.0000000000002099
    [10]
    Weiland T J, Hadgkiss E J, Jelinek G A, et al. The association of alcohol consumption and smoking with quality of life, disability and disease activity in an international sample of people with multiple sclerosis. J. Neurol. Sci., 2014, 336: 211–219. doi: 10.1016/j.jns.2013.10.046
    [11]
    Kvistad S, Myhr K M, Holmøy T, et al. No association of tobacco use and disease activity in multiple sclerosis. Neurol. Neuroimmunol. Neuroinflamm., 2016, 3 (4): e260. doi: 10.1212/NXI.0000000000000260
    [12]
    Briggs F B S, Yu J C, Davis M F, et al. Multiple sclerosis risk factors contribute to onset heterogeneity. Mult. Scler. Relat. Disord., 2019, 28: 11–16. doi: 10.1016/j.msard.2018.12.007
    [13]
    Petersen E R, Søndergaard H B, Laursen J H, et al. Smoking is associated with increased disease activity during natalizumab treatment in multiple sclerosis. Mult. Scler., 2019, 25 (9): 1298–1305. doi: 10.1177/1352458518791753
    [14]
    Polman C H, Reingold S C, Banwell B, et al. Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald criteria. Ann. Neurol., 2011, 69 (2): 292–302. doi: 10.1002/ana.22366
    [15]
    Thompson A J, Banwell B L, Barkhof F, et al. Diagnosis of multiple sclerosis: 2017 revisions of the McDonald criteria. Lancet Neurol., 2018, 17 (2): 162–173. doi: 10.1016/S1474-4422(17)30470-2
    [16]
    Wingerchuk D M, Banwell B, Bennett J L, et al. International consensus diagnostic criteria for neuromyelitis optica spectrum disorders. Neurology, 2015, 85 (2): 177–189. doi: 10.1212/WNL.0000000000001729
    [17]
    Hedström A K, Olsson T, Alfredsson L. Smoking is a major preventable risk factor for multiple sclerosis. Mult. Scler., 2016, 22 (8): 1021–1026. doi: 10.1177/1352458515609794
    [18]
    Kurtzke J F. Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS). Neurology, 1983, 33 (11): 1444–1452. doi: 10.1212/WNL.33.11.1444
    [19]
    Roxburgh R H S R, Seaman S R, Masterman T, et al. Multiple Sclerosis Severity Score: Using disability and disease duration to rate disease severity. Neurology, 2005, 64 (7): 1144–1151. doi: 10.1212/01.WNL.0000156155.19270.F8
    [20]
    Kalincik T. Multiple sclerosis relapses: epidemiology, outcomes and management. A systematic review. Neuroepidemiology, 2015, 44 (4): 199–214. doi: 10.1159/000382130
    [21]
    Tettey P, Simpson S Jr, Taylor B, et al. An adverse lipid profile is associated with disability and progression in disability, in people with MS. Mult. Scler., 2014, 20 (13): 1737–1744. doi: 10.1177/1352458514533162
    [22]
    Manouchehrinia A, Tench C R, Maxted J, et al. Tobacco smoking and disability progression in multiple sclerosis: United Kingdom cohort study. Brain, 2013, 136: 2298–2304. doi: 10.1093/brain/awt139
    [23]
    Ivashynka A, Copetti M, Naldi P, et al. The impact of lifetime alcohol and cigarette smoking loads on multiple sclerosis severity. Front. Neurol., 2019, 10: 866. doi: 10.3389/fneur.2019.00866
    [24]
    Paz-Ballesteros W C, Monterrubio-Flores E A, de Jesús Flores-Rivera J, et al. Cigarette smoking, alcohol consumption and overweight in multiple sclerosis: disability progression. Arch. Med. Res., 2017, 48 (1): 113–120. doi: 10.1016/j.arcmed.2017.03.002
    [25]
    D'hooghe M B, Haentjens P, Nagels G, et al. Alcohol, coffee, fish, smoking and disease progression in multiple sclerosis. Eur. J. Neurol., 2012, 19 (4): 616–624. doi: 10.1111/j.1468-1331.2011.03596.x
    [26]
    Kinga M, Balasa R. Effect of serum 25(OH) D level, cigarette smoking and oral contraceptive use on clinical course of relapsing-remitting multiple sclerosis in a group of female patients. Romanian Journal of Neurology, 2015, 14 (4): 214–218. doi: 10.37897/RJN.2015.4.5
    [27]
    Al Wutayd O, Mohamed A G, Saeedi J, et al. Environmental exposures and the risk of multiple sclerosis in Saudi Arabia. BMC Neurol., 2018, 18 (1): 86. doi: 10.1186/s12883-018-1090-8
    [28]
    Tao C, Simpson S Jr, Taylor B V, et al. Onset symptoms, tobacco smoking, and progressive-onset phenotype are associated with a delayed onset of multiple sclerosis, and marijuana use with an earlier onset. Front. Neurol., 2018, 9: 418. doi: 10.3389/fneur.2018.00418
    [29]
    McDowell T Y, Amr S, Culpepper W J, et al. Sun exposure, vitamin D and age at disease onset in relapsing multiple sclerosis. Neuroepidemiology, 2011, 36 (1): 39–45. doi: 10.1159/000322512
    [30]
    Hedström A K, Hillert J, Olsson T, et al. Smoking and multiple sclerosis susceptibility. Eur. J. Epidemiol., 2013, 28 (11): 867–874. doi: 10.1007/s10654-013-9853-4
    [31]
    Hedstrom A K, Baarnhielm M, Olsson T, et al. Tobacco smoking, but not Swedish snuff use, increases the risk of multiple sclerosis. Neurology, 2009, 73 (9): 696–701. doi: 10.1212/WNL.0b013e3181b59c40
    [32]
    Alrouji M, Manouchehrinia A, Gran B, et al. Effects of cigarette smoke on immunity, neuroinflammation and multiple sclerosis. J. Neuroimmunol., 2019, 329: 24–34. doi: 10.1016/j.jneuroim.2018.10.004
    [33]
    Jin H J, Li H T, Sui H X, et al. Nicotine stimulated bone marrow-derived dendritic cells could augment HBV specific CTL priming by activating PI3K-Akt pathway. Immunol. Lett., 2012, 146: 40–49. doi: 10.1016/j.imlet.2012.02.015
    [34]
    Gao Z, Nissen J C, Ji K, et al. The experimental autoimmune encephalomyelitis disease course is modulated by nicotine and other cigarette smoke components. PLoS One, 2014, 9 (9): e107979. doi: 10.1371/journal.pone.0107979
    [35]
    de Jonge W J, Ulloa L. The alpha7 nicotinic acetylcholine receptor as a pharmacological target for inflammation. Br. J. Pharmacol., 2007, 151 (7): 915–929. doi: 10.1038/sj.bjp.0707264
    [36]
    Tracey K J. Physiology and immunology of the cholinergic antiinflammatory pathway. J. Clin. Invest., 2007, 117 (2): 289–296. doi: 10.1172/JCI30555
    [37]
    Filippini P, Cesario A, Fini M, et al. The Yin and Yang of non-neuronal α7-nicotinic receptors in inflammation and autoimmunity. Curr. Drug Targets, 2012, 13 (5): 644–655. doi: 10.2174/138945012800399008
  • 加载中

Catalog

    Figure  1.  Kaplan‒Meier analysis of (a, b) time to relapse in the MS cohort and (c, d) time to relapse in the NMOSD cohort.

    [1]
    Höftberger R, Lassmann H. Inflammatory demyelinating diseases of the central nervous system. Handb. Clin. Neurol., 2017, 145: 263–283. doi: 10.1016/B978-0-12-802395-2.00019-5
    [2]
    Lennon V A, Wingerchuk D M, Kryzer T J, et al. A serum autoantibody marker of neuromyelitis optica: distinction from multiple sclerosis. Lancet, 2004, 364 (9451): 2106–2112. doi: 10.1016/S0140-6736(04)17551-X
    [3]
    Tian D C, Zhang C Y, Yuan M, et al. Incidence of multiple sclerosis in China: A nationwide hospital-based study. Lancet Reg. Health West. Pac., 2020, 1: 100010. doi: 10.1016/j.lanwpc.2020.100010
    [4]
    Rosso M, Chitnis T. Association between cigarette smoking and multiple sclerosis: A review. JAMA Neurol., 2020, 77 (2): 245–253. doi: 10.1001/jamaneurol.2019.4271
    [5]
    Messina S, Mariano R, Geraldes R, et al. The influence of smoking on the pattern of disability and relapse risk in AQP4-positive Neuromyelitis Optica Spectrum Disorder, MOG-Ab Disease and Multiple Sclerosis. Mult. Scler. Relat. Disord., 2021, 49: 102773. doi: 10.1016/j.msard.2021.102773
    [6]
    Lavery A M, Collins B N, Waldman A T, et al. The contribution of secondhand tobacco smoke exposure to pediatric multiple sclerosis risk. Mult. Scler., 2019, 25 (4): 515–522. doi: 10.1177/1352458518757089
    [7]
    Pittas F, Ponsonby A L, van der Mei I A F, et al. Smoking is associated with progressive disease course and increased progression in clinical disability in a prospective cohort of people with multiple sclerosis. J. Neurol., 2009, 256 (4): 577–585. doi: 10.1007/s00415-009-0120-2
    [8]
    Petersen E R, Oturai A B, Koch-Henriksen N, et al. Smoking affects the interferon beta treatment response in multiple sclerosis. Neurology, 2018, 90 (7): e593–e600. doi: 10.1212/WNL.0000000000004949
    [9]
    Munger K L, Fitzgerald K C, Freedman M S, et al. No association of multiple sclerosis activity and progression with EBV or tobacco use in BENEFIT. Neurology, 2015, 85 (19): 1694–1701. doi: 10.1212/WNL.0000000000002099
    [10]
    Weiland T J, Hadgkiss E J, Jelinek G A, et al. The association of alcohol consumption and smoking with quality of life, disability and disease activity in an international sample of people with multiple sclerosis. J. Neurol. Sci., 2014, 336: 211–219. doi: 10.1016/j.jns.2013.10.046
    [11]
    Kvistad S, Myhr K M, Holmøy T, et al. No association of tobacco use and disease activity in multiple sclerosis. Neurol. Neuroimmunol. Neuroinflamm., 2016, 3 (4): e260. doi: 10.1212/NXI.0000000000000260
    [12]
    Briggs F B S, Yu J C, Davis M F, et al. Multiple sclerosis risk factors contribute to onset heterogeneity. Mult. Scler. Relat. Disord., 2019, 28: 11–16. doi: 10.1016/j.msard.2018.12.007
    [13]
    Petersen E R, Søndergaard H B, Laursen J H, et al. Smoking is associated with increased disease activity during natalizumab treatment in multiple sclerosis. Mult. Scler., 2019, 25 (9): 1298–1305. doi: 10.1177/1352458518791753
    [14]
    Polman C H, Reingold S C, Banwell B, et al. Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald criteria. Ann. Neurol., 2011, 69 (2): 292–302. doi: 10.1002/ana.22366
    [15]
    Thompson A J, Banwell B L, Barkhof F, et al. Diagnosis of multiple sclerosis: 2017 revisions of the McDonald criteria. Lancet Neurol., 2018, 17 (2): 162–173. doi: 10.1016/S1474-4422(17)30470-2
    [16]
    Wingerchuk D M, Banwell B, Bennett J L, et al. International consensus diagnostic criteria for neuromyelitis optica spectrum disorders. Neurology, 2015, 85 (2): 177–189. doi: 10.1212/WNL.0000000000001729
    [17]
    Hedström A K, Olsson T, Alfredsson L. Smoking is a major preventable risk factor for multiple sclerosis. Mult. Scler., 2016, 22 (8): 1021–1026. doi: 10.1177/1352458515609794
    [18]
    Kurtzke J F. Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS). Neurology, 1983, 33 (11): 1444–1452. doi: 10.1212/WNL.33.11.1444
    [19]
    Roxburgh R H S R, Seaman S R, Masterman T, et al. Multiple Sclerosis Severity Score: Using disability and disease duration to rate disease severity. Neurology, 2005, 64 (7): 1144–1151. doi: 10.1212/01.WNL.0000156155.19270.F8
    [20]
    Kalincik T. Multiple sclerosis relapses: epidemiology, outcomes and management. A systematic review. Neuroepidemiology, 2015, 44 (4): 199–214. doi: 10.1159/000382130
    [21]
    Tettey P, Simpson S Jr, Taylor B, et al. An adverse lipid profile is associated with disability and progression in disability, in people with MS. Mult. Scler., 2014, 20 (13): 1737–1744. doi: 10.1177/1352458514533162
    [22]
    Manouchehrinia A, Tench C R, Maxted J, et al. Tobacco smoking and disability progression in multiple sclerosis: United Kingdom cohort study. Brain, 2013, 136: 2298–2304. doi: 10.1093/brain/awt139
    [23]
    Ivashynka A, Copetti M, Naldi P, et al. The impact of lifetime alcohol and cigarette smoking loads on multiple sclerosis severity. Front. Neurol., 2019, 10: 866. doi: 10.3389/fneur.2019.00866
    [24]
    Paz-Ballesteros W C, Monterrubio-Flores E A, de Jesús Flores-Rivera J, et al. Cigarette smoking, alcohol consumption and overweight in multiple sclerosis: disability progression. Arch. Med. Res., 2017, 48 (1): 113–120. doi: 10.1016/j.arcmed.2017.03.002
    [25]
    D'hooghe M B, Haentjens P, Nagels G, et al. Alcohol, coffee, fish, smoking and disease progression in multiple sclerosis. Eur. J. Neurol., 2012, 19 (4): 616–624. doi: 10.1111/j.1468-1331.2011.03596.x
    [26]
    Kinga M, Balasa R. Effect of serum 25(OH) D level, cigarette smoking and oral contraceptive use on clinical course of relapsing-remitting multiple sclerosis in a group of female patients. Romanian Journal of Neurology, 2015, 14 (4): 214–218. doi: 10.37897/RJN.2015.4.5
    [27]
    Al Wutayd O, Mohamed A G, Saeedi J, et al. Environmental exposures and the risk of multiple sclerosis in Saudi Arabia. BMC Neurol., 2018, 18 (1): 86. doi: 10.1186/s12883-018-1090-8
    [28]
    Tao C, Simpson S Jr, Taylor B V, et al. Onset symptoms, tobacco smoking, and progressive-onset phenotype are associated with a delayed onset of multiple sclerosis, and marijuana use with an earlier onset. Front. Neurol., 2018, 9: 418. doi: 10.3389/fneur.2018.00418
    [29]
    McDowell T Y, Amr S, Culpepper W J, et al. Sun exposure, vitamin D and age at disease onset in relapsing multiple sclerosis. Neuroepidemiology, 2011, 36 (1): 39–45. doi: 10.1159/000322512
    [30]
    Hedström A K, Hillert J, Olsson T, et al. Smoking and multiple sclerosis susceptibility. Eur. J. Epidemiol., 2013, 28 (11): 867–874. doi: 10.1007/s10654-013-9853-4
    [31]
    Hedstrom A K, Baarnhielm M, Olsson T, et al. Tobacco smoking, but not Swedish snuff use, increases the risk of multiple sclerosis. Neurology, 2009, 73 (9): 696–701. doi: 10.1212/WNL.0b013e3181b59c40
    [32]
    Alrouji M, Manouchehrinia A, Gran B, et al. Effects of cigarette smoke on immunity, neuroinflammation and multiple sclerosis. J. Neuroimmunol., 2019, 329: 24–34. doi: 10.1016/j.jneuroim.2018.10.004
    [33]
    Jin H J, Li H T, Sui H X, et al. Nicotine stimulated bone marrow-derived dendritic cells could augment HBV specific CTL priming by activating PI3K-Akt pathway. Immunol. Lett., 2012, 146: 40–49. doi: 10.1016/j.imlet.2012.02.015
    [34]
    Gao Z, Nissen J C, Ji K, et al. The experimental autoimmune encephalomyelitis disease course is modulated by nicotine and other cigarette smoke components. PLoS One, 2014, 9 (9): e107979. doi: 10.1371/journal.pone.0107979
    [35]
    de Jonge W J, Ulloa L. The alpha7 nicotinic acetylcholine receptor as a pharmacological target for inflammation. Br. J. Pharmacol., 2007, 151 (7): 915–929. doi: 10.1038/sj.bjp.0707264
    [36]
    Tracey K J. Physiology and immunology of the cholinergic antiinflammatory pathway. J. Clin. Invest., 2007, 117 (2): 289–296. doi: 10.1172/JCI30555
    [37]
    Filippini P, Cesario A, Fini M, et al. The Yin and Yang of non-neuronal α7-nicotinic receptors in inflammation and autoimmunity. Curr. Drug Targets, 2012, 13 (5): 644–655. doi: 10.2174/138945012800399008

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