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Aging and Disease    2014, Vol. 5 Issue (2) : 126-136     DOI: 10.14336/AD.2014.0500126
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Sepsis in Old Age: Review of Human and Animal Studies
Marlene E Starr1, 3, Hiroshi Saito1, 2, 3, *
1Department of Surgery, Lexington, KY 40536, USA
2Department of Physiology, Lexington, KY 40536, USA
3Markey Cancer Center University of Kentucky, Lexington, KY 40536, USA
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Abstract  

Sepsis is a serious problem among the geriatric population as its incidence and mortality rates dramatically increase with advanced age. Despite a large number of ongoing clinical and basic research studies, there is currently no effective therapeutic strategy that rescues elderly patients with severe sepsis. Recognition of this problem is relatively low as compared to other age-associated diseases. The disparity between clinical and basic studies is a problem, and this is likely due, in part, to the fact that most laboratory animals used for sepsis research are not old while the majority of sepsis cases occur in the geriatric population. The objective of this article is to review recent epidemiological studies and clinical observations, and compare these with findings from basic laboratory studies which have used aged animals in experimental sepsis.

Keywords aging      animal models      coagulation      elderly      inflammation      sepsis     
Corresponding Authors: Hiroshi Saito   
Issue Date: 10 March 2014
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Marlene E Starr,Hiroshi Saito. Sepsis in Old Age: Review of Human and Animal Studies[J]. Aging and Disease, 2014, 5(2): 126-136.
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http://www.aginganddisease.org/EN/10.14336/AD.2014.0500126     OR     http://www.aginganddisease.org/EN/Y2014/V5/I2/126
[1] Podnos YD, Jimenez JC, Wilson SE(2002). Intra-abdominal Sepsis in Elderly Persons. Clin Infect Dis, 35:62-68
[2] Kale SS, Yende S(2011). Effects of Aging on Inflammation and Hemostasis through the Continuum of Critical Illness. Aging Dis, 2:501-511
[3] Opal SM, Girard TD, Ely EW(2005). The immunopathogenesis of sepsis in elderly patients. Clin Infect Dis, 41(Suppl 7):S504-512
[4] Pisani MA(2009). Considerations in caring for the critically ill older patient. J Intensive Care Med, 24:83-95
[5] Wier M, Andrews RM(2011). The National Hospital Bill: The Most Expensive Conditions by Payer, 2008HCUPVol. Statistical Brief #107
[6] Andrews R, Elixhauser A(2007). The National Hospital Bill: Growth Trends and 2005 Update on the Most Expensive Conditions by Payer. Healthcare Costs and Utilization ProjectVol. Statistical Brief #42
[7] Angus DC, van der Poll T(2013). Severe sepsis and septic shock. N Engl J Med, 369:2063
[8] Torpy JM, Lynm C, Glass RM(2009). JAMA patient page. Intensive care units. JAMA, 301:1304
[9] Angus DC, Linde-Zwirble WT, Lidicker J, Clermont G, Carcillo J, Pinsky MR(2001). Epidemiology of severe sepsis in the United States: analysis of incidence, outcome, and associated costs of care. Crit Care Med, 29:1303-1310
[10] Vincent JL, Sakr Y, Sprung CL, Ranieri VM, Reinhart K, Gerlach H(2006). Sepsis in European intensive care units: results of the SOAP study. Crit Care Med, 34:344-353
[11] Esper AM, Moss M, Lewis CA, Nisbet R, Mannino DM, Martin GS(2006). The role of infection and comorbidity: Factors that influence disparities in sepsis. Crit Care Med, 34:2576-2582
[12] Alberti C, Brun-Buisson C, Burchardi H, Martin C, Goodman S, Artigas A(2002). Epidemiology of sepsis and infection in ICU patients from an international multicentre cohort study. Intensive Care Med, 28:108-121
[13] Cavaillon JM, Adib-Conquy M, Fitting C, Adrie C, Payen D(2003). Cytokine cascade in sepsis. Scand J Infect Dis, 35:535-544
[14] Philippart F, Cavaillon J, Dinarello C(2009). Inflammatory Mediators. Sepsis and Non-infectious Systemic Inflammation, Cavaillon J, Adrie C 177-204Wiley-VCHWeinheim
[15] Iskander KN, Osuchowski MF, Stearns-Kurosawa DJ, Kurosawa S, Stepien D, Valentine C(2013). Sepsis: multiple abnormalities, heterogeneous responses, and evolving understanding. Physiol Rev, 93:1247-1288
[16] Esmon CT, Fukudome K, Mather T, Bode W, Regan LM, Stearns-Kurosawa DJ(1999). Inflammation, sepsis, and coagulation. Haematologica, 84:254-259
[17] Opal SM, Esmon CT(2003). Bench-to-bedside review: functional relationships between coagulation and the innate immune response and their respective roles in the pathogenesis of sepsis. Crit Care, 7:23-38
[18] Dellinger RP, Levy MM, Rhodes A, Annane D, Gerlach H, Opal SM(2013). Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: 2012. Crit Care Med, 41:580-637
[19] Lagu T, Rothberg MB, Shieh MS, Pekow PS, Steingrub JS, Lindenauer PK(2012). Hospitalizations, costs, and outcomes of severe sepsis in the United States 2003 to 2007. Crit Care Med, 40:754-761
[20] Dombrovskiy VY, Martin AA, Sunderram J, Paz HL(2007). Rapid increase in hospitalization and mortality rates for severe sepsis in the United States: a trend analysis from 1993 to 2003. Crit Care Med, 35:1244-1250
[21] Wester AL, Dunlop O, Melby KK, Dahle UR, Wyller TB(2013). Age-related differences in symptoms, diagnosis and prognosis of bacteremia. BMC Infect Dis, 13:346
[22] Girard TD, Opal SM, Ely EW(2005). Insights into severe sepsis in older patients: from epidemiology to evidence-based management. Clin Infect Dis, 40:719-727
[23] Girard TD, Ely EW(2007). Bacteremia and sepsis in older adults. Clin Geriatr Med, 23:633-647 viii
[24] Martin GS, Mannino DM, Eaton S, Moss M(2003). The epidemiology of sepsis in the United States from 1979 through 2000. N Engl J Med, 348:1546-1554
[25] Gaieski DF, Edwards JM, Kallan MJ, Carr BG(2013). Benchmarking the incidence and mortality of severe sepsis in the United States. Crit Care Med, 41:1167-1174
[26] Heron M(2012). Deaths: Leading causes for 2009, Statistics NCfH 61Hyattsville, MD
[27] Martin GS, Mannino DM, Moss M(2006). The effect of age on the development and outcome of adult sepsis. Crit Care Med, 34:15-21
[28] Reade M, Angus D(2009). Epidemiology of Sepsis and Non-infectious SIRS. Sepsis and Non-infectious Systemic Inflammation, Cavaillon J, Adrie C 13-39Wiley-VCHWeinheim
[29] Ely EW, Angus DC, Williams MD, Bates B, Qualy R, Bernard GR(2003). Drotrecogin alfa (activated) treatment of older patients with severe sepsis. Clin Infect Dis, 37:187-195
[30] Carbajal-Guerrero J, Cayuela-Dominguez A, Fernandez-Garcia E, Aldabo-Pallas T, Marquez-Vacaro JA, Ortiz-Leyba C(2013). Epidemiology and long-term outcome of sepsis in elderly patients[published online ahead of print Feb 22, 2013]. Med Intensiva,doi 10.1016/j.medin.2012.12.006
[31] Lemay AC, Anzueto A, Restrepo MI, Mortensen EM(2013). Predictors of Long-term Mortality After Severe Sepsis in the Elderly[published online ahead of print May 17, 2013].Am J Med Scidoi 10.1097/MAJ.0b013e318295a147
[32] De Gaudio AR, Rinaldi S, Chelazzi C, Borracci T(2009). Pathophysiology of sepsis in the elderly: clinical impact and therapeutic considerations. Curr Drug Targets, 10:60-70
[33] Miller RA(1996). The aging immune system: primer and prospectus. Science, 273:70-74
[34] Grubeck-Loebenstein B, Berger P, Saurwein-Teissl M, Zisterer K, Wick G(1998). No immunity for the elderly. Nat Med, 4:870
[35] Chou JP, Effros RB(2013). T cell replicative senescence in human aging. Curr Pharm Des, 19:1680-1698
[36] McElhaney JE, Effros RB(2009). Immunosenescence: what does it mean to health outcomes in older adults?. Curr Opin Immunol, 21:418-424
[37] Dewan SK, Zheng SB, Xia SJ, Bill K(2012). Senescent remodeling of the immune system and its contribution to the predisposition of the elderly to infections. Chin Med J (Engl)125:3325-3331
[38] Weksler ME, Goodhardt M, Szabo P(2002). The effect of age on B cell development and humoral immunity. Springer Semin Immunopathol, 24:35-52
[39] Gomez CR, Nomellini V, Faunce DE, Kovacs EJ(2008). Innate immunity and aging. Exp Gerontol, 43:718-728
[40] Cohen HJ, Harris T, Pieper CF(2003). Coagulation and activation of inflammatory pathways in the development of functional decline and mortality in the elderly. Am J Med, 114:180-187
[41] Krabbe KS, Pedersen M, Bruunsgaard H(2004). Inflammatory mediators in the elderly. Exp Gerontol, 39:687-699
[42] Walston J, McBurnie MA, Newman A, Tracy RP, Kop WJ, Hirsch CH(2002). Frailty and activation of the inflammation and coagulation systems with and without clinical comorbidities: results from the Cardiovascular Health Study. Arch Intern Med, 162:2333-2341
[43] Kale S, Yende S, Kong L, Perkins A, Kellum JA, Newman AB(2010). The effects of age on inflammatory and coagulation-fibrinolysis response in patients hospitalized for pneumonia. PLoS One, 5:e13852
[44] Naffaa M, Makhoul BF, Tobia A, Kaplan M, Aronson D, Saliba W(2013). Interleukin-6 at discharge predicts all-cause mortality in patients with sepsis. Am J Emerg Med, 31:1361-1364
[45] Marik PE, Zaloga GP(2001). The effect of aging on circulating levels of proinflammatory cytokines during septic shock. Norasept II Study Investigators. J Am Geriatr Soc, 49:5-9
[46] Bruunsgaard H, Skinhoj P, Qvist J, Pedersen BK(1999). Elderly humans show prolonged in vivo inflammatory activity during pneumococcal infections. J Infect Dis, 180:551-554
[47] Boldt J, Muller M, Heesen M, Papsdorf M, Hempelmann G(1997). Does age influence circulating adhesion molecules in the critically ill?. Crit Care Med, 25:95-100
[48] Levi M(2010). The coagulant response in sepsis and inflammation. Hamostaseologie, 30:10-12 14-16
[49] Levi M, de Jonge E, van der Poll T(2003). Sepsis and disseminated intravascular coagulation. J Thromb Thrombolysis, 16:43-47
[50] Mari D, Mannucci PM, Coppola R, Bottasso B, Bauer KA, Rosenberg RD(1995). Hypercoagulability in centenarians: the paradox of successful aging. Blood, 85:3144-3149
[51] Alexander SL, Ernst FR(2006). Use of drotrecogin alfa (activated) in older patients with severe sepsis. Pharmacotherapy, 26:533-538
[52] Seok J, Warren HS, Cuenca AG, Mindrinos MN, Baker HV, Xu W(2013). Genomic responses in mouse models poorly mimic human inflammatory diseases. Proc Natl Acad Sci U S A, 110:3507-3512
[53] Zanotti-Cavazzoni SL, Goldfarb RD(2009). Animal models of sepsis. Crit Care Clin, 25:703-719
[54] Flurkey K, Currer J, Harrison D(2007). Mouse Models in Aging Research. The Mouse in Biomedical Research, Fox JG 637-372
[55] Rittirsch D, Hoesel LM, Ward PA(2007). The disconnect between animal models of sepsis and human sepsis. J Leukoc Biol, 81:137-143
[56] Esmon CT(2004). Why do animal models (sometimes) fail to mimic human sepsis?. Crit Care Med, 32:S219-222
[57] Nomellini V, Gomez CR, Kovacs EJ(2008). Aging and impairment of innate immunity. Contrib Microbiol, 15:188-205
[58] Kovacs EJ, Palmer JL, Fortin CF, Fulop TJr, Goldstein DR, Linton PJ(2009). Aging and innate immunity in the mouse: impact of intrinsic and extrinsic factors. Trends Immunol, 30:319-324
[59] Finch C(1990). Longevity, senescence, and the genomeUniversity of Chicago PressChicago
[60] Okamura D, Starr ME, Lee EY, Stromberg AJ, Evers BM, Saito H(2012). Age-dependent vulnerability to experimental acute pancreatitis is associated with increased systemic inflammation and thrombosis. Aging Cell, 11:760-769
[61] Saito H, Papaconstantinou J(2001). Age-associated differences in cardiovascular inflammatory gene induction during endotoxic stress. J Biol Chem, 276:29307-29312
[62] Saito H, Sherwood ER, Varma TK, Evers BM(2003). Effects of aging on mortality, hypothermia, and cytokine induction in mice with endotoxemia or sepsis. Mech Ageing Dev, 124:1047-1058
[63] Starr ME, Evers BM, Saito H(2009). Age-associated increase in cytokine production during systemic inflammation: adipose tissue as a major source of IL-6. J Gerontol A Biol Sci Med Sci, 64:723-730
[64] Starr ME, Hu Y, Stromberg AJ, Carmical JR, Wood TG, Evers BM(2013). Gene expression profile of mouse white adipose tissue during inflammatory stress: age-dependent upregulation of major procoagulant factors. Aging Cell, 12:194-206
[65] Starr ME, Saito H(2012). Age-related increase in food spilling by laboratory mice may lead to significant overestimation of actual food consumption: implications for studies on dietary restriction, metabolism, and dose calculations. J Gerontol A Biol Sci Med Sci, 67:1043-1048
[66] Starr ME, Ueda J, Takahashi H, Weiler H, Esmon CT, Evers BM(2010). Age-dependent vulnerability to endotoxemia is associated with reduction of anticoagulant factors activated protein C and thrombomodulin. Blood, 115:4886-4893
[67] Starr ME, Ueda J, Yamamoto S, Evers BM, Saito H(2011). The effects of aging on pulmonary oxidative damage, protein nitration and extracellular superoxide dismutase down-regulation during systemic inflammation. Free Radic Biol Med, 50:371-380
[68] Hubbard WJ, Choudhry M, Schwacha MG, Kerby JD, Rue LW3rd, Bland KI(2005). Cecal ligation and puncture. Shock, 24(Suppl 1):52-57
[69] Rittirsch D, Huber-Lang MS, Flierl MA, Ward PA(2009). Immunodesign of experimental sepsis by cecal ligation and puncture. Nat Protoc, 4:31-36
[70] Ebong S, Call D, Nemzek J, Bolgos G, Newcomb D, Remick D(1999). Immunopathologic alterations in murine models of sepsis of increasing severity. Infect Immun, 67:6603-6610
[71] Turnbull IR, Wlzorek JJ, Osborne D, Hotchkiss RS, Coopersmith CM, Buchman TG(2003). Effects of age on mortality and antibiotic efficacy in cecal ligation and puncture. Shock, 19:310-313
[72] Turnbull IR, Clark AT, Stromberg PE, Dixon DJ, Woolsey CA, Davis CG(2009). Effects of aging on the immunopathologic response to sepsis. Crit Care Med, 37:1018-1023
[73] Drechsler S, Weixelbaumer K, Raeven P, Jafarmadar M, Khadem A, van Griensven M(2012). Relationship between age/gender-induced survival changes and the magnitude of inflammatory activation and organ dysfunction in post-traumatic sepsis. PLoS One, 7:e51457
[74] Gomez CR, Goral J, Ramirez L, Kopf M, Kovacs EJ(2006). Aberrant acute-phase response in aged interleukin-6 knockout mice. Shock, 25:581-585
[75] Habicht GS(1981). Body temperature in normal and endotoxin-treated mice of different ages. Mech Ageing Dev, 16:97-104
[76] Chorinchath BB, Kong LY, Mao L, McCallum RE(1996). Age-associated differences in TNF-alpha and nitric oxide production in endotoxic mice. J Immunol, 156:1525-1530
[77] Tateda K, Matsumoto T, Miyazaki S, Yamaguchi K(1996). Lipopolysaccharide-induced lethality and cytokine production in aged mice. Infect Immun, 64:769-774
[78] Horan MA, Brouwer A, Barelds RJ, Wientjens R, Durham SK, Knook DL(1991). Changes in endotoxin sensitivity in ageing. Absorption, elimination and mortality. Mech Ageing Dev, 57:145-162
[79] Emmerling P, Hof H, Finger H(1979). Age-related defense against infection with intracellular pathogens. Gerontology, 25:327-336
[80] Patel PJ(1981). Aging and cellular defense mechanisms: age-related changes in resistance of mice to Listeria monocytogenes. Infect Immun, 32:557-562
[81] Tocco-Bradley R, Kluger MJ, Kauffman CA(1985). Effect of age on fever and acute-phase response of rats to endotoxin and Salmonella typhimurium. Infect Immun, 47:106-111
[82] Louria DB, Lavenhar MA, Kaminski T, Buse M, Kaplan M(1986). Staphylococcal infections in aging mice. J Gerontol, 41:718-722
[83] Orme IM(1987). Aging and immunity to tuberculosis: increased susceptibility of old mice reflects a decreased capacity to generate mediator T lymphocytes. J Immunol, 138:4414-4418
[84] Maddens B, Vandendriessche B, Demon D, Vanholder R, Chiers K, Cauwels A(2012). Severity of sepsis-induced acute kidney injury in a novel mouse model is age dependent. Crit Care Med, 40:2638-2646
[85] Antonini JM, Roberts JR, Clarke RW, Yang HM, Barger MW, Ma JY(2001). Effect of age on respiratory defense mechanisms: pulmonary bacterial clearance in Fischer 344 rats after intratracheal instillation of Listeria monocytogenes. Chest, 120:240-249
[86] Mares CA, Sharma J, Ojeda SS, Li Q, Campos JA, Morris EG(2010). Attenuated response of aged mice to respiratory Francisella novicida is characterized by reduced cell death and absence of subsequent hypercytokinemia. PLoS One, 5:e14088
[87] Esposito AL, Pennington JE(1983). Effects of aging on antibacterial mechanisms in experimental pneumonia. Am Rev Respir Dis, 128:662-667
[88] Little CS, Bowe A, Lin R, Litsky J, Fogel RM, Balin BJ(2005). Age alterations in extent and severity of experimental intranasal infection with Chlamydophila pneumoniae in BALB/c mice. Infect Immun, 73:1723-1734
[89] Shivshankar P, Boyd AR, Le Saux CJ, Yeh IT, Orihuela CJ(2011). Cellular senescence increases expression of bacterial ligands in the lungs and is positively correlated with increased susceptibility to pneumococcal pneumonia. Aging Cell, 10:798-806
[90] Southam DS, Dolovich M, O’Byrne PM, Inman MD(2002). Distribution of intranasal instillations in mice: effects of volume, time, body position, and anesthesia. Am J Physiol Lung Cell Mol Physiol, 282:L833-839
[91] Hyde SR, McCallum RE(1992). Lipopolysaccharide-tumor necrosis factor-glucocorticoid interactions during cecal ligation and puncture-induced sepsis in mature versus senescent mice. Infect Immun, 60:976-982
[92] Wu R, Zhou M, Dong W, Ji Y, Miksa M, Marini CP(2009). Ghrelin hyporesponsiveness contributes to age-related hyperinflammation in septic shock. Ann Surg, 250:126-133
[93] Akaiwa M, Yu B, Umeshita-Suyama R, Terada N, Suto H, Koga T(2001). Localization of human interleukin 13 receptor in non-haematopoietic cells. Cytokine, 13:75-84
[94] Foster KD, Conn CA, Kluger MJ(1992). Fever, tumor necrosis factor, and interleukin-6 in young, mature, and aged Fischer 344 rats. Am J Physiol, 262:R211-215
[95] Zhou M, Wu R, Dong W, Leong J, Wang P(2010). Accelerated apoptosis contributes to aging-related hyperinflammation in endotoxemia. Int J Mol Med, 25:929-935
[96] Remick DG, Bolgos GR, Siddiqui J, Shin J, Nemzek JA(2002). Six at six: interleukin-6 measured 6 h after the initiation of sepsis predicts mortality over 3 days. Shock, 17:463-467
[97] Remick DG, Bolgos G, Copeland S, Siddiqui J(2005). Role of interleukin-6 in mortality from and physiologic response to sepsis. Infect Immun, 73:2751-2757
[98] Xing Z, Gauldie J, Cox G, Baumann H, Jordana M, Lei XF(1998). IL-6 is an antiinflammatory cytokine required for controlling local or systemic acute inflammatory responses. J Clin Invest, 101:311-320
[99] Ulich TR, Guo KZ, Remick D, del Castillo J, Yin SM(1991). Endotoxin-induced cytokine gene expression in vivo. III. IL-6 mRNA and serum protein expression and the in vivo hematologic effects of IL-6. J Immunol, 146:2316-2323
[100] Saito H, Patterson C, Hu Z, Runge MS, Tipnis U, Sinha M(2000). Expression and self-regulatory function of cardiac interleukin-6 during endotoxemia. Am J Physiol Heart Circ Physiol, 279:H2241-2248
[101] Riedemann NC, Neff TA, Guo RF, Bernacki KD, Laudes IJ, Sarma JV(2003). Protective effects of IL-6 blockade in sepsis are linked to reduced C5a receptor expression. J Immunol, 170:503-507
[102] Clemmer TP, Fisher CJJr, Bone RC, Slotman GJ, Metz CA, Thomas FO(1992). Hypothermia in the sepsis syndrome and clinical outcome. The Methylprednisolone Severe Sepsis Study Group. Crit Care Med, 20:1395-1401
[103] Tiruvoipati R, Ong K, Gangopadhyay H, Arora S, Carney I, Botha J(2010). Hypothermia predicts mortality in critically ill elderly patients with sepsis. BMC Geriatr, 10:70
[104] Gomez CR, Nomellini V, Baila H, Oshima K, Kovacs EJ(2009). Comparison of the effects of aging and IL-6 on the hepatic inflammatory response in two models of systemic injury: scald injury versus i.p. LPS administration. Shock, 31:178-184
[105] Gomez CR, Hirano S, Cutro BT, Birjandi S, Baila H, Nomellini V(2007). Advanced age exacerbates the pulmonary inflammatory response after lipopolysaccharide exposure. Crit Care Med, 35:246-251
[106] Tucsek Z, Gautam T, Sonntag WE, Toth P, Saito H, Salomao R(2013). Aging exacerbates microvascular endothelial damage induced by circulating factors present in the serum of septic patients. J Gerontol A Biol Sci Med Sci, 68:652-660
[107] Turnbull IR, Buchman TG, Javadi P, Woolsey CA, Hotchkiss RS, Karl IE(2004). Age disproportionately increases sepsis-induced apoptosis in the spleen and gut epithelium. Shock, 22:364-368
[108] Hotchkiss RS, Swanson PE, Freeman BD, Tinsley KW, Cobb JP, Matuschak GM(1999). Apoptotic cell death in patients with sepsis, shock, and multiple organ dysfunction. Crit Care Med, 27:1230-1251
[109] Le Tulzo Y, Pangault C, Gacouin A, Guilloux V, Tribut O, Amiot L(2002). Early circulating lymphocyte apoptosis in human septic shock is associated with poor outcome. Shock, 18:487-494
[110] Roger PM, Hyvernat H, Ticchioni M, Kumar G, Dellamonica J, Bernardin G(2012). The early phase of human sepsis is characterized by a combination of apoptosis and proliferation of T cells. J Crit Care, 27:384-393
[111] Gharacholou SM, Becker RC(2009). Hemostasis and thrombosis in older adults. J Thromb Thrombolysis, 27:249-251
[112] Wilkerson WR, Sane DC(2002). Aging and thrombosis. Semin Thromb Hemost, 28:555-568
[113] Yamamoto K, Shimokawa T, Yi H, Isobe K, Kojima T, Loskutoff DJ(2002). Aging accelerates endotoxin-induced thrombosis: increased responses of plasminogen activator inhibitor-1 and lipopolysaccharide signaling with aging. Am J Pathol, 161:1805-1814
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