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CNS Infections pp 273-297 | Cite as

Central Nervous System Infections in Patients Immunocompromised by Antineoplastic and Other Immune-Modulating Therapies

  • Amy A. PruittEmail author
Chapter

Abstract

Central nervous system (CNS) infections in patients receiving immunosuppressive therapy for cancer or other systemic conditions often present complex diagnostic challenges as signs of infection may be absent or atypical. This chapter outlines a systematic clinical approach based on the etiology of immunosuppression, general examination, and presence of concurrent systemic infections. Patients with impaired barrier function, neutropenia, B cell depletion, and T cell abnormalities are included. The laboratory and imaging diagnosis, management, and prognosis of infections such as PML, VZV, human herpesvirus 6, and fungal infections likely to be seen by practicing neurologists are discussed and contrasted with conditions that mimic infection. Infections associated with mycophenolate, cyclosporine, tacrolimus, rituximab, brentuximab, and alemtuzumab are described. Human immunodeficiency virus-associated infections are covered in Chap. 15.

Keywords

Aspergillus Corticosteroids Limbic encephalitis Listeria Natalizumab Progressive multifocal leukoencephalopathy Rituximab Tacrolimus Tumor necrosis Alpha inhibitors Varicella-zoster virus 

References

  1. 1.
    Tan IL, McArthur JC, Ventaesan A, Nath A. Atypical manifestations and poor outcome of herpes simplex encephalitis in the immunocompromised. Neurology. 2012;79:2125–32.PubMedCentralPubMedCrossRefGoogle Scholar
  2. 2.
    Safdieh JE, Mead PA, Sepkowitz KA, Kiehn TE, Abrey LE. Bacterial and fungal meningitis in patients with cancer. Neurology. 2008;70(12):943–7.PubMedCrossRefGoogle Scholar
  3. 3.
    Pruitt AA. CNS infections in patients with cancer. Continuum Lifelong Learning Neurol. 2012;18(2):384–405.CrossRefGoogle Scholar
  4. 4.
    Kranick SM, Vinnard C, Kolson DL. Propionibacterium acnes brain abscess appearing 10 years after neurosurgery. Arch Neurol. 2009;66(6):793–5.PubMedGoogle Scholar
  5. 5.
    Pruitt AA. Central nervous system infections in cancer patients. Semin Neurol. 2010;30(3):296–310.PubMedCrossRefGoogle Scholar
  6. 6.
    Clark AJ, Butowski NA, Chang SM, et al. Impact of bevacizumab chemotherapy on craniotomy wound healing. J Neurosurg. 2011;114(6):1609–16.PubMedCrossRefGoogle Scholar
  7. 7.
    Suzuki HI, Hangaishi A, Hosoya N, et al. Herpes simplex encephalitis and subsequent cytomegalovirus encephalitis after chemoradiotherapy for central nervous system lymphoma: a case report and literature review. Int J Hematol. 2008;87(5):538–41.PubMedCrossRefGoogle Scholar
  8. 8.
    Kocher M, Kunze S, Eich HT, et al. Efficacy and toxicity of postoperative temozolomide radiochemotherapy in malignant glioma. Strahlenter Onkol. 2005;181(3):157–63.CrossRefGoogle Scholar
  9. 9.
    Pruitt AA, Graus F, Rosenfeld MR. Neurological complications of transplantation. Part I: hematopoietic cell transplantation. Neurohospitalist. 2013;3:24–38. Part II: solid organ transplantation. Neurohospitalist. 2013;3:152–66.PubMedCentralPubMedCrossRefGoogle Scholar
  10. 10.
    Siegal D, Keller A, Xu W, et al. Central nervous system complications after allogeneic hematopoietic stem cell transplantation: incidence, manifestations and clinical significance. Biol Blood Marrow Transplant. 2007;13(11):1369–79.PubMedCrossRefGoogle Scholar
  11. 11.
    Bhanushali MJ, Kranick SM, Freeman AF, Cuellar-Rodriguez JM, Battiwalla M, Gea-Banacloche JC, et al. Human herpes 6 virus encephalitis complicating allogeneic hematopoietic stem cell transplantation. Neurology. 2013;80:1494–500.PubMedCentralPubMedCrossRefGoogle Scholar
  12. 12.
    Nath A, Berger JR. Complications of immunomodulatory therapy in neurological diseases. Curr Treat Options Neurol. 2012;14:241–55.PubMedCrossRefGoogle Scholar
  13. 13.
    Nagel MA, Gilden DH. The protean neurologic manifestations of varicella-zoster virus infection. Cleve Clin J Med. 2007;74(7):489–94.PubMedCrossRefGoogle Scholar
  14. 14.
    Salazar R, Russman AN, Nagel MA, et al. VZV temporal arteritis and subclinical temporal artery involvement. Arch Neurol. 2011;68:517–20.PubMedCentralPubMedCrossRefGoogle Scholar
  15. 15.
    Nagel MA, Russman AN, Feit DO, Schmid DS, Gilden D. VZV ischemic optic neuropathy and subclinical temporal artery infection without rash. Neurology. 2013;80:220–2.PubMedCentralPubMedCrossRefGoogle Scholar
  16. 16.
    Gilden D, Cohrs RJ, Mahalingam R, et al. Varicella zoster vasculopathies: diverse clinical manifestations, laboratory features, pathogenesis and treatment. Lancet Neurol. 2009;8(8):731–40.PubMedCentralPubMedCrossRefGoogle Scholar
  17. 17.
    Styczynski J, Reusser P, Einsele H, et al. Management of HSV, VZV and EBV infections in patients with hematological malignancies and after stem cell transplantation: guidelines from the Second European Conference on Infections in Leukemia. Bone Marrow Transplant. 2009;43(10):757–70.PubMedCrossRefGoogle Scholar
  18. 18.
    Day JN, Chau TTH, Wolbers M, Mai PP, Dung NT, Mai NH, et al. Combination antifungal therapy for cryptococcal meningitis. N Engl J Med. 2013;268(14):1291–302.CrossRefGoogle Scholar
  19. 19.
    Labbe AC, Su SH, Laverdiere M, et al. High incidence of invasive aspergillosis associated with intestinal graft-versus-host disease following nonmyeloablative transplantation. Biol Blood Marrow Transplant. 2007;13(10):1192–200.PubMedCrossRefGoogle Scholar
  20. 20.
    Evens AM, Roy R, Sterrenberg D, et al. Post-transplantation lymphoproliferative disorders: diagnosis, prognosis and current approaches to therapy. Curr Oncol Rep. 2010;12(6):383–94.PubMedCrossRefGoogle Scholar
  21. 21.
    Tan CS, Ellis LC, Wuthrich C, et al. JC virus latency in the brain and extraneural organs of patients with and without progressive multifocal leukoencephalopathy. J Virol. 2010;84:9200–9.PubMedCentralPubMedCrossRefGoogle Scholar
  22. 22.
    Tan CS, Koralnik IJ. Progressive multifocal leukoencephalopathy and other disorders caused by JC virus: clinical features and pathogenesis. Lancet Neurol. 2010;9:425–37.PubMedCentralPubMedCrossRefGoogle Scholar
  23. 23.
    Schmedt N, Andersohn F, Garbe E. Signals of progressive multifocal leukoencephalopathy for immunosuppressants: a disproportionality analysis of spontaneous reports within the US Adverse Event Reporting System (AERS). Pharmacoepidemiol Drug Saf. 2012;21:1216–20.PubMedCrossRefGoogle Scholar
  24. 24.
    Bosch X, Saiz A, Ramos-Casals M, and the BIOGEAS Study Group. Monoclonal antibody therapy-associated neurological disorders. Nat Rev Neurol. 2011;7:165–72.PubMedCrossRefGoogle Scholar
  25. 25.
    Gheuens S, Pierone G, Peeters P, et al. Progressive multifocal leukoencephalopathy in individuals with minimal or occult immunosuppression. J Neurol Neurosurg Psychiatry. 2010;81:247–54.PubMedCentralPubMedCrossRefGoogle Scholar
  26. 26.
    McGuire JL, Fridman V, Wuthrich C, Koralnik IJ, Jacobs D. Progressive multifocal leukoencephalopathy associated with isolated CD8+ T-lymphocyte deficiency mimicking tumefactive MS. J Neurovirol. 2011;17(5):500–3.PubMedCentralPubMedCrossRefGoogle Scholar
  27. 27.
    Koralnik IM, Wuthrich C, Dang X, et al. JC virus granule cell neuronopathy: a novel clinical syndrome distinct from progressive multifocal leukoencephalopathy. Ann Neurol. 2005;57:576–80.PubMedCrossRefGoogle Scholar
  28. 28.
    Wuthrich C, Dang X, Westmoreland S, et al. Fulminant JC virus encephalopathy with productive infection of cortical pyramidal neurons. Ann Neurol. 2009;65:742–8.PubMedCentralPubMedCrossRefGoogle Scholar
  29. 29.
    Berger JR, Aksamit AJ, Clifford DB, Davis L, Koralnik IJ, Sejvar JJ, et al. PML diagnostic criteria: consensus statement from the AAN Neuroinfectious Disease Section. Neurology. 2013;80:1430–8.PubMedCentralPubMedCrossRefGoogle Scholar
  30. 30.
    Horger M, Beschorner R, Beck R, Nagele T, Schulze M, Ernemann U, Heckl S. Common and uncommon imaging findings in progressive multifocal leukoencephalopathy (PML) with differential diagnostic considerations. Clin Neurol Neruosurg. 2012;114:1123–30.CrossRefGoogle Scholar
  31. 31.
    Mateen FJ, Muralidharan RN, Carone M, van de Beek D, Harrison DM, Aksamit AJ, et al. Progressive multifocal leukoencephalopathy in transplant recipients. Ann Neurol. 2011;70:305–22.PubMedCrossRefGoogle Scholar
  32. 32.
    Clifford DB, Nath A, Cinque P, Brew BJ, Zivadinov R, Gorelik L, et al. A study of mefloquine treatment for progressive multifocal leukoencephalopathy: results and exploration of predictors of PML outcomes. J Neurovirol. 2013;19(4):351–8.Google Scholar
  33. 33.
    Brew BJ, Davies NWS, Cinque P, Cliffor DB, Nath A. Progressive multifocal leukoencephalopathy and other forms of JC virus disease. Nat Rev Neurol. 2010;6:667–79.PubMedCrossRefGoogle Scholar
  34. 34.
    Kleinschmidt-DeMasters BK, Tyler KL. Progressive multifocal leukoencephalopathy complicating treatment with natalizumab and interferon beta-1a for multiple sclerosis. N Engl J Med. 2005;353:369–74.PubMedCrossRefGoogle Scholar
  35. 35.
    Langer-Gould A, Atlas SW, Green AJ, et al. Progressive multifocal leukoencephalopathy in a patient treated with natalizumab. N Engl J Med. 2005;353:375–81.PubMedCrossRefGoogle Scholar
  36. 36.
    Van Assche G, Van Ranst M, Sciot R, et al. Progressive multifocal leukoencephalopathy after natalizumab therapy for Crohn’s disease. N Engl J Med. 2005;353:362–8.PubMedCrossRefGoogle Scholar
  37. 37.
    Clifford DB, DeLuca A, Simpson DM, Arendt G, Giovannoni G, Nath A. Natalizumab-associated progressive multifocal leukoencephalopathy in patients with multiple sclerosis: lessons from 28 cases. Lancet Neurol. 2010;9:438–46.PubMedCrossRefGoogle Scholar
  38. 38.
    Tan IL, McArthur JC, Clifford DB, Major E, Nath A. Immune reconstitution inflammatory syndrome in natalizumab – associated PML. Neurology. 2011;77:1061–7.PubMedCentralPubMedCrossRefGoogle Scholar
  39. 39.
    Linda H, von Heijne A, Major EO, et al. Progressive multifocal leukoencephalopathy after natalizumab monotherapy. N Engl J Med. 2009;361:1081–7.PubMedCrossRefGoogle Scholar
  40. 40.
    Gorelik L, Lerner M, Bixler S, et al. Anti-JCV antibodies: implications for PML risk stratification. Ann Neurol. 2010;68:392–5.CrossRefGoogle Scholar
  41. 41.
    Aksamit AJ. Progressive multifocal leukoencephalopathy. Continuum Lifelong Learning Neurol. 2012;18(6):1374–91.CrossRefGoogle Scholar
  42. 42.
    Chen Y. Asymptomatic reactivation of JC virus in patients treated with natalizumab. N Engl J Med. 2009;361:1067–74.PubMedCentralPubMedCrossRefGoogle Scholar
  43. 43.
    Major EO, Frohman E, Douek D. JC viremia in natalizumab-treated patients with multiple sclerosis. N Engl J Med. 2013;368(23):2240–1.PubMedCentralPubMedCrossRefGoogle Scholar
  44. 44.
    Rudick RA, O’Connor PW, Goelz SE, et al. Assessment of JC virus DNA in blood and urine from natalizumab-treated patients. Ann Neurol. 2010;68:304–10.PubMedCrossRefGoogle Scholar
  45. 45.
    West T, Cree B. Natalizumab dosage suspension: are we helping or hurting? Ann Neurol. 2010;68:395–9.PubMedCrossRefGoogle Scholar
  46. 46.
    Killestein J, Vennegoor A, Striijbis EM, et al. Natalizumab drug holiday in multiple sclerosis: poorly tolerated. Ann Neurol. 2010;68:392–3935.PubMedCrossRefGoogle Scholar
  47. 47.
    Lenhard T, Biller A, Mueller W, et al. Immune reconstitution inflammatory syndrome after withdrawal of natalizumab? Neurology. 2010;75:831–3.PubMedCrossRefGoogle Scholar
  48. 48.
    Miravalle A, Jense R, Kinkel RP. Immune reconstitution inflammatory syndrome in patients with multiple sclerosis following cessation of natalizumab therapy. Arch Neurol. 2011;68:186–91.PubMedGoogle Scholar
  49. 49.
    Ryschkewitsch CF, Jensen PN, Major EO, et al. JC virus persistence following PML in MS patients treated with natalizumab. Ann Neurol. 2010;68:384–91.PubMedCentralPubMedCrossRefGoogle Scholar
  50. 50.
    Antoniol C, Jilek S, Schluep M, Mercier N, Canales M, Le Goff G, et al. Impairment of JCV-specific T-cell response by corticotherapy. Effect on PML-IRIS management. Neurology. 2012;79:2258–64.PubMedCrossRefGoogle Scholar
  51. 51.
    Aktos O, Kury P, Kieseier B, et al. Fingolimod is a potential novel therapy for multiple sclerosis. Nat Rev Neurol. 2010;6:373–82.CrossRefGoogle Scholar
  52. 52.
    Gross CM, Baumgartner A, Rauer S, Stich O. Multiple sclerosis rebound following herpes zoster infection and suspension of fingolimod. Neurology. 2012;79:2006–7.PubMedCrossRefGoogle Scholar
  53. 53.
    Ratchford JN, Costell K, Riech DS, Calabresisi PA. Varicella zoster virus encephalitis and vasculopathy in a patient treated with fingolimod. Neurology. 2012;79:20020–2004.CrossRefGoogle Scholar
  54. 54.
    Van Oosten BW, Killestien J, Barkhof F, Polman CH, Wattjes MP. PML in a patient treated with dimethyl fumarate from a compounding pharmacy. N Engl J Med. 2013;368(17):1658–9.PubMedCrossRefGoogle Scholar
  55. 55.
    Ermis U, Weis J, Schulz JB. PML in a patient treated with fumaric acid. N Engl J Med. 2013;268(17):1657–8.CrossRefGoogle Scholar
  56. 56.
    Sweetser MT, Dawson KT, Bozic C. Manufacturer’s response to case reports of PML. N Engl J Med. 2013;368(17):1659–60.PubMedCrossRefGoogle Scholar
  57. 57.
    Perez-Alvarez R, Perez-de-Lis M, Ramos-Casals M, on behalf of the BIOGEAS Study Group. Curr Opin Rheumatol. 2013;25(1):56–64.PubMedCrossRefGoogle Scholar
  58. 58.
    Molloy ES, Calabrese LH. Progressive multifocal leukoencephalopathy associated with immunosuppressive therapy in rheumatoid diseases. Arthritis Rheum. 2012;64(9):3043–51.PubMedCrossRefGoogle Scholar
  59. 59.
    Keene DL, Legare C, Taylor E, Gallivan J, Cawthorn GM, Vu D. Monoclonal antibodies and progressive multifocal leukoencephalopathy. Can J Neurol Sci. 2011;38:565–71.PubMedGoogle Scholar
  60. 60.
    Piccinni C, Sacripanti C, Poluzzi E, Motola D, Magro L, Moretti U, et al. Stronger association of drug-induced progressive multifocal leukoencephalopathy (PML) with biological immunomodulating agents. Eur J Clin Pharmacol. 2010;66:199–206.PubMedCrossRefGoogle Scholar
  61. 61.
    Molloy ES, Calabrese LH. Progressive multifocal leukoencephalopathy: a national estimate of frequency in SLE and other rheumatic diseases. Arthritis Rheum. 2009;60:3761–5.PubMedCrossRefGoogle Scholar
  62. 62.
    Carson KR, Focosi D, Major EO, Petrini M, Richey EA, West DP, Bennett CI. Monoclonal antibody-associated progressive multifocal leukoencephalopathy in patients treated with rituximab, natalizumab and efalizumab: a review from the Research on Adverse Drug Events and Reports (RADAR) project. Lancet Oncol. 2009;10:816–24.PubMedCrossRefGoogle Scholar
  63. 63.
    Major EO. Progressive multifocal leukoencephalopathy in patients on immunomodulatory therapies. Annu Rev Med. 2010;61:35–47.PubMedCrossRefGoogle Scholar
  64. 64.
    Gea-Banacloche JC. Rituximab-associated infections. Semin Hematol. 2010;47(2):187–98.PubMedCrossRefGoogle Scholar
  65. 65.
    Ganjoo KN, Raman R, Sobel RA, et al. Opportunistic enteroviral meningoencephalitis: an unusual treatable complication of rituximab therapy. Leuk Lymphoma. 2009;50(4):673–5.PubMedCrossRefGoogle Scholar
  66. 66.
    Levi ME, Quan D, Ho JT, et al. Impact of rituximab-associated B-cell defects on West Nile virus meningoencephalitis in solid organ transplant recipients. Clin Transplant. 2009;24(2):223–8.PubMedCentralPubMedCrossRefGoogle Scholar
  67. 67.
    Lee MY, Chiou TJ, Hsaiao LT, et al. Rituximab therapy increased post-transplant cytomegalovirus complications in non-Hodgkin lymphoma patients receiving autologous hematopoietic stem cell transplantation. Ann Hematol. 2008;87(4):285–9.PubMedCrossRefGoogle Scholar
  68. 68.
    Tuccori M, Focosi D, Blandizzi C, Pelosini M, Montangni S, Maggi F, et al. Inclusion of rituximab in treatment protocols for non-Hodgkin’s lymphomas and risk for progressive multifocal leukoencephalopathy. Oncologist. 2010;15:1214–9.PubMedCentralPubMedCrossRefGoogle Scholar
  69. 69.
    D’Souza A, Wilson J, Mukherjee S, Jaiyesimi I. Progressive multifocal leukoencephalopathy in chronic lymphocytic leukemia. A report of 3 cases and review of the literature. Clin Lymphoma Myeloma Leuk. 2010;10(1):E1–9.PubMedCrossRefGoogle Scholar
  70. 70.
    Tyler KL. Progressive multifocal leukoencephalopathy: can we reduce risk in patients receiving biological immunomodulatory therapies? Ann Neurol. 2010;68(3):271–4.PubMedCrossRefGoogle Scholar
  71. 71.
    Korman BD, Tyler KL, Korman NJ. Progressive multifocal leukoencephalopathy, efalizumab, and immunosuppression. A cautionary tale for dermatologists. Arch Dermatol. 2009;145(8):937–40.PubMedCrossRefGoogle Scholar
  72. 72.
    Clifford DB, Ances B, Costello C, Rosen-Schmidt S, Andersson M, Parks D, et al. Rituximab-associated progressive multifocal leukoencephalopathy in rheumatoid arthritis. Arch Neurol. 2011;68(9):1156–64.PubMedCentralPubMedCrossRefGoogle Scholar
  73. 73.
    Salliot C, Dougados M, Gossec L. Risk of serious infections during rituximab, abatacept and anakinra treatments for rheumatoid arthritis: meta-analyses of randomised placebo-controlled trials. Ann Rheum Dis. 2009;68:25–32.PubMedCentralPubMedCrossRefGoogle Scholar
  74. 74.
    Schwab N, Ulzheimer JC, Fox RJ, et al. Fatal progressive multifocal leukoencephalopathy associated with efalizumab therapy: insights into the role of leukointegrin aLb2in JC virus control. Mult Scler. 2009;15:S271–7.CrossRefGoogle Scholar
  75. 75.
    Von Geldern G, Pardo CA, Calabresi PA, Newsome SD. PML-IRIS in a patient treated with brentuximab. Neurology. 2012;79:2075–7.CrossRefGoogle Scholar
  76. 76.
    Jalan P, Mahajan A, Pandav V, Bekker S, Koirala J. Brentuximab associated progressive multifocal leukoencephalopathy. Clin Neurol Neurosurg. 2012;114:1335–7.PubMedCrossRefGoogle Scholar
  77. 77.
    Tsang HH, Trendell-Smith NJ, Wu AK, et al. Diffuse large B-cell lymphoma of the CNS in mycophenolate mofetil-treated patients with systemic lupus erythematosus. Lupus. 2010;19:330–3.PubMedCrossRefGoogle Scholar
  78. 78.
    Berger JR. Progressive multifocal leukoencephalopathy and newer biological agents. Drug Saf. 2010;33(11):969–83.PubMedCrossRefGoogle Scholar
  79. 79.
    Neff RT, Hurst GP, Falta EM, Bohen EM, Lentine KL, Dharnidharka VR, et al. Progressive multifocal leukoencephalopathy and use of mycophenolate mofetil after kidney transplantation. Transplantation. 2008;86:1474–8.PubMedCrossRefGoogle Scholar
  80. 80.
    Strangfeld A, Lising J, Herzer P, et al. Risk of herpes zoster in patients with rheumatoid arthritis treated with anti-TNF-alpha agents. JAMA. 2009;301:737–44.PubMedCrossRefGoogle Scholar
  81. 81.
    Whitfield RJ, Gnann JW. Herpes zoster in the age of focused immunosuppressive therapy. JAMA. 2009;301:774–5.CrossRefGoogle Scholar
  82. 82.
    Wolfe F, Michaud K, Chakravarty EF. Rates and predictors of herpes zoster in patients with rheumatoid arthritis and non-inflammatory musculoskeletal disorders. Rheumatology. 2006;45:1370–5.PubMedCrossRefGoogle Scholar
  83. 83.
    Harpaz R, Ortega-Sanchez IR, Seward JF. Advisory Committee on Immunization Practices (ACIP), Centers for Disease Control and Prevention. Prevention of herpes zoster: recommendations of the ACIP (published correction appears in MMWR Recomm Rep 2008;57:779). MMWR Recomm Rep. 2008;57(RR-5):1–30.Google Scholar
  84. 84.
    Lysandropoulos AP, Du Pasquier RA. Demyelination as a complication of new immunomodulatory treatments. Curr Opin Neurol. 2010;23:226–33.PubMedCrossRefGoogle Scholar
  85. 85.
    Li S, Birnbaum AD, Goldstein DA. Optic neuritis associated with adalimumab in the treatment of uveitis. Ocul Immunol Inflamm. 2010;18:L475–81.CrossRefGoogle Scholar
  86. 86.
    Armstrong RJE, Elston JS, Hatton CS, et al. De novo relapsing-remitting multiple sclerosis following autologous stem cell transplantation. Neurology. 2010;75:89–90.PubMedCrossRefGoogle Scholar
  87. 87.
    Fugate JE, Claassen DO, Cloft HJ. Posterior reversible encephalopathy syndrome: associated clinical and radiologic findings. Mayo Clin Proc. 2010;85:427–32.PubMedCentralPubMedCrossRefGoogle Scholar
  88. 88.
    Nozaki K, Silver RM, Stickler DE, Abou-Fayssal NG, Giglio P, Kamen DL, et al. Neurological deficits during treatment with tumor necrosis factor-alpha antagonists. Am J Med Sci. 2011;342(5):352–5.PubMedCrossRefGoogle Scholar
  89. 89.
    National Multiple Sclerosis Society (NMSS). 2013. Available from http://www.nationalmssociety.org.

Copyright information

© Springer-Verlag London 2014

Authors and Affiliations

  1. 1.Department of NeurologyUniversity of Pennsylvania, Perelman School of MedicinePhiladelphiaUSA

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