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Interpreting the Mechanisms of CRRT in Sepsis: The Peak Concentration Hypothesis

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Intensive Care Medicine

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Abstract

Acute renal failure is increasingly seen as part of the multiple organ dysfunction syndrome (MODS) in critically ill patients [1, 2]. MODS is the most frequent cause of death in patients admitted to intensive care units (ICUs) [3]. Severe sepsis and septic shock are the primary causes of MODS [4, 5] and develop as a result of the host response to infection by Gram-negative and Gram-positive bacteria [6]. Sepsis encompasses a complex mosaic of interconnected events. Molecules such as bacterial lipopolysaccharides (LPS), microbial lipopeptides, microbial DNA, peptidoglycan and lipoteichoic acid interact with the Toll-like receptors (TLR) and related molecules (MD-2, MyD88), the principal sensors of the innate immune response [7–9]. Stimulus-receptor coupling activates different signal transduction pathways leading to exacerbated generation of cytokines, and phospholipase A2-dependent, arachidonic acid-derived platelet-activating factor (PAF), leukotrienes, and thromboxanes. At the plasma level, activation of the complement (C3a, C5a, and their desarginated products) and coagulation pathways interacts with the process as products generated in the fluid phase may in turn trigger and sustain cell activation. Other agents play a role in the pathophysiology of sepsis such as surface-expressed and soluble adhesion molecules, kinins, thrombin, myocardial depressant substance(s), endorphin, and heat shock proteins.

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References

  1. Cosentino F, Chaff C, Piedmonte M (1994) Risk factors influencing survival in ICU acute renal failure. Nephrol Dial Transplant 9 (suppl 4): 179–182

    PubMed  Google Scholar 

  2. Liano G, Pascual J (1996) Acute renal failure. Madrid Acute Renal Failure Study Group. Lancet 347: 479

    Google Scholar 

  3. Bellomo R, Ronco C (1998) Indications and criteria for initiating renal replacement therapy in the intensive care unit. Kidney Int Suppl 66: S106–5109

    PubMed  CAS  Google Scholar 

  4. The ACCP/SCCM Consensus conference committee (1992) Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. Chest 101: 1644–1655

    Article  Google Scholar 

  5. Camussi G, Montrucchio G, Diminioni L, Dionigi R (1995) Septic shock: the unravelling of molecular mechanism. Nephrol Dial Transplant 10: 1808–1813

    PubMed  CAS  Google Scholar 

  6. Glauser MP, Zanetti G, Baumgartner JD, Cohen J (1991) Septic shock: pathogenesis. Lancet 338: 732–736

    Article  PubMed  CAS  Google Scholar 

  7. Medzhitov R, Preston-Hurlburt P, Janeway CA Jr (1997) A human homologue of the Drosophila Toll protein signals activation of adaptive immunity. Nature 388: 394–397

    Article  PubMed  CAS  Google Scholar 

  8. Shimazu R, Akashi S, Ogata H, et al (1999) MD-2 a molecule that confers lipopolysaccharide responsiveness on Toll-like receptor 4. J Exp Med 189: 1777–1782

    Article  PubMed  CAS  Google Scholar 

  9. Medzhitov R, Preston-Hurlburt P, Kopp E, et al (1998) My88 is an adaptor protein in the hToll/IL-1 receptor family signaling pathways. Mol Cell 2: 253–258

    Article  PubMed  CAS  Google Scholar 

  10. Van Bommel EFH, Bouvy ND, So KL, et al (1995) Acute dialytic support for the critically ill: Intermittent hemodialysis versus continuous arteriovenous hemodiafiltration. Am J Nephrol 15: 192–200

    Article  PubMed  Google Scholar 

  11. Bellomo R, Mehta R (1995) Acute renal replacement in the intensive care medicine: Now and tomorrow. New Horiz 3: 760–767

    PubMed  CAS  Google Scholar 

  12. Canaud B, Mion C (1995) Extracorporeal treatment of acute renal failure: methods, indications, quantified and personalized therapeutic approach. Adv Nephrol 24: 271–281

    CAS  Google Scholar 

  13. Silvester W, Bellomo R, Ronco C (1998) Continuous versus intermittent renal replacement therapy in the critically ill. In: Ronco C, Bellomo R (eds) Critical Care Nephrology. Kluwer Academic Publishers, Dordrecht, pp 1225–1238

    Chapter  Google Scholar 

  14. Bellomo R, Tipping P, Boyce N (1993) Continuous veno-venous hemofiltration with dialysis cytokines from the circulation of septic patients. Crit Care Med 21: 522–526

    Article  PubMed  CAS  Google Scholar 

  15. Schetz M, Ferdinande P, Van der Berghe G, et al (1995) Removal of pro-inflammatory cytokines with renal replacement therapy: sense or nonsense? Intensive Care Med 21: 169–176

    Article  PubMed  CAS  Google Scholar 

  16. Van Bommel EFH, Hesse CJ, Jutte NHPM, et al (1995) Cytokine kinetics during continuous hemofiltration: a laboratory and clinical study. Contrib Nephrol 116: 62–75

    PubMed  Google Scholar 

  17. Bellomo R, Tipping P, Boyce N (1995) Interleukin-6 and interleukin-8 extraction during continuous venovenous-hemodiafiltration in septic acute renal failure. Renal Fail 17: 457–466

    Article  CAS  Google Scholar 

  18. Millar AB, Armstrong L, van der Linden J, et al (1993) Cytokine production and hemofiltration in children undergoing cardiopulmonary bypass. Ann Thorac Surg 56: 1499–1502

    Article  PubMed  CAS  Google Scholar 

  19. Journois D, Pouard P, Greely WJ, et al (1994) Hemofiltration during cardiopulmonary bypass in pediatric cardiac surgery. Anesthesiology 81: 1181–1189

    Article  PubMed  CAS  Google Scholar 

  20. Goldfarb S, Golper TA (1994) Proinflammatory cytokines and hemofiltration membranes. J Am Soc Nephrol 5: 228–232

    PubMed  CAS  Google Scholar 

  21. Ronco C, Tetta C, Lupi A, et al (1995) Removal of platelet-activating factor in experimental continuous arteriovenous hemofiltration. Crit Care Med 23: 99–107

    Article  PubMed  CAS  Google Scholar 

  22. Cavaillon JM, Munoz C, Fitting C, et al (1992) Circulating cytokines: The top of the iceberg? Circ Shock 38: 145–152

    PubMed  CAS  Google Scholar 

  23. Reidy MA, Bowyer DE (1997) Scanning electron microscopy: morphology of aortic endothelium following injury by endotoxin and during subsequent repair. Atherosclerosis 26: 319–328

    Article  Google Scholar 

  24. Gil LY, Rosellò AM, Torres AC, et al (2002) Modulation of soluble phases of endothelial/ leukocyte adhesion molecule 1, intercellular adhesion molecule 1, and vascular cell adhesion molecule 1 with interleukin lß after experimental endotoxic challenge. Crit Care Med (in press)

    Google Scholar 

  25. Dinarello CA, Cannon JC, Wolff SM, et al (1986) Tumor necrosis factor (cachectin) is an endogenous pyrogen and induces production of interleukin 1. J Exp Med 163: 1433–1440

    Article  PubMed  CAS  Google Scholar 

  26. van Deventer SJH, Bueller HR, ten Cate JW, et al (1990) Experimental endotoxemia in humans: analysis of cytokine release and coagulation, fibrinolytic and complement pathways. Blood 76: 2520–2526

    PubMed  Google Scholar 

  27. Rosenberg RD, Aird WC (1999) Vascular-bed specific hemostasis and hypercoagulable states. N Engl J Med 340: 1555–1564

    Article  PubMed  CAS  Google Scholar 

  28. Esmon CT (2000) The protein C pathway. Crit Care Med 28: S44 - S48

    Article  PubMed  CAS  Google Scholar 

  29. Taylor FB, Haddad PA, Hack E, et al (2001). Two-stage response to endotoxin infusion into normal human subjects:Correlation of blood phagocyte luminescence with clinical and laboratory markers of the inflammatory, hemostatic response. Crit Care Med 29: 326–334

    Article  PubMed  CAS  Google Scholar 

  30. Faust SN, Levin M, Harrison OB, et al (2001) Dysfunction of endothelial protein C activation in severe meningococcal sepsis. N Engl J Med 345: 408–416

    Article  PubMed  CAS  Google Scholar 

  31. Pinsky MR (2001) Sepsis: a pro-and anti-inflammatory disequilibrium syndrome. Contrib Nephrol 132: 354–366

    Article  PubMed  CAS  Google Scholar 

  32. Cavaillon JM, Adib-Conquy M, Cloez-Tayarani I, Fitting C (2001) Immunodepression in sepsis and SIRS assessed by ex vivo cytokine production is not a generalized phenomenon: a review. J Endotoxin Res 7: 85–93

    PubMed  CAS  Google Scholar 

  33. Suffredini AF, Fromm RE, Parker MM, et al (1989) The cardiovascular response of normal humans to the administration of endotoxin. N Engl J Med 321: 280–287

    Article  PubMed  CAS  Google Scholar 

  34. Matrich GD, Danner RL, Ceska M, et al (1991) Detection of interleukin 8 and tumor necrosis factor in normal humans after intravenous endotoxin: The effect of antiinflammatory agents. J Exp Med 173: 1021–1024

    Article  Google Scholar 

  35. Michie HR, Manogue KR, Spriggs DR, et al (1988) Detection of circulating tumor necrosis factor after endotoxin administration. N Engl J Med 318: 1481–1486

    Article  PubMed  CAS  Google Scholar 

  36. Suffredini AF, Harpel PC, Parrillo JE (1989) Promotion and subsequent inhibition of plasminogen activator after administration of intravenous endotoxin to normal subjects. N Engl J Med 320: 1165–1172

    Article  PubMed  CAS  Google Scholar 

  37. Kumasaka T, Quinlan W, Doyle N, et al (1996) Role of the intercellular adhesion molecule (ICAM-1) in endotoxin-induced pneumonitis using ICAM-1 anti-sense oligonucleotides, anti-ICAM-1 monoclonal antibodies and ICAM-1 mutant mice. J Clin Invest 97: 2362–2369

    Article  PubMed  CAS  Google Scholar 

  38. Volk HD, Reinke P, Krausch D, et al (1996) Monocyte deactivation: rationale for a new therapeutic strategy in sepsis. Intensive Care Med (suppl 4 ): 5474 - S481

    Google Scholar 

  39. Cavaillon JM, Adib-Conquy M, Cloez-Tayarani I, Fitting C (2001) Immunosuppression in sepsis and SIRS assessed by ex-vivo cytokine production is not a generalized phenomenon: a review. J Endotoxin Res 7: 85–93

    PubMed  CAS  Google Scholar 

  40. Munoz C, Carlet J, Fitting C, et al (1991) Dysregulation of in vitro cytokine production by monocytes during sepsis. J Clin Invest 88: 1747–1754

    Article  PubMed  CAS  Google Scholar 

  41. Randow F, Syrbe V, Meisel C, et al (1995) Mechanism of endotoxin desensitization: involvement of interleukin-10 and transforming growth factor. J Exp Med 181: 1887–1892

    Article  PubMed  CAS  Google Scholar 

  42. Brandtzaeg P, Osnes L, Ostebo R, et al (1996) Net inflammatory capacity of human septic shock plasma evaluated by a monocyte-based target cell assay: identification of interleukin-10 as a major functional deactivator of human monocytes. J Exp Med 184: 51–60

    Article  PubMed  CAS  Google Scholar 

  43. Marie C, Muret J, Fitting C, et al (2000) Interleukin-1 receptor antagonist production during infectious and noninfectious systemic inflammatory response syndrome. Crit Care Med 28: 2277–2282

    Article  PubMed  CAS  Google Scholar 

  44. Granowitz EV, Porat R, Mier JW, et al (1993) Intravenous endotoxin suppresses the cytokine response of peripheral blood mononuclear cells in healthy humans. J Immunol 151: 1637–1645

    PubMed  CAS  Google Scholar 

  45. Knudsen PJ, Dinarello CA, Strom TB (1986) Prostaglandins posttranscriptionally inhibit monocyte expression of interleukin 1 activity by increasing intracellular cyclic adenosine monophosphate. J Immunol 137: 3189–3194

    PubMed  CAS  Google Scholar 

  46. Bone RC, Grodzin CJ, Balk RA (1997) Sepsis: A new hypothesis for pathogenesis of the disease process. Chest 112: 235–243

    Google Scholar 

  47. Adib-Conquy M, Adrie C, Moine P, et al (2000) NF-kappaB expression in mononuclear cells of patients with sepsis resembles that observed in lipopolysaccharide tolerance. Am J Respir Crit Care Med 162: 1877–1883

    Article  PubMed  CAS  Google Scholar 

  48. Gogos CA, Drosou E, Bassaris HP, Skoutelis A (2000) Pro-versus anti-inflammatory cytokine profile in patients with severe sepsis: a marker for prognosis and future therapeutic options. J Infect Dis 181: 176–180

    Article  PubMed  CAS  Google Scholar 

  49. Parrillo JE, Burch C, Stelhamer JH, et al (1985) A circulating myocardial depressant substance in humans with septic shock: septic shock patients with a reduced ejection fraction have a circulating factor that depresses in vitro myocardial cell performance. J Clin Invest 76: 1539–1553

    Article  PubMed  CAS  Google Scholar 

  50. Zeni F, Freeman B, Natanson C (1997) Anti-inflammatory therapies to treat sepsis and septic shock: a reassessment. Crit Care Med 25: 1095–1100

    Article  PubMed  CAS  Google Scholar 

  51. Abraham E, Glauser MP, Butler T, et al (1997) p55 tumor necrosis factor receptor fusion protein in the treatment of patients with severe sepsis and septic shock. A randomized controlled multicenter trial. Ro 45–2081 study group. JAMA 277: 1531–1538

    Google Scholar 

  52. Fisher CJ, Agosti JM, Opal SM (1996) Treatment of septic shock with the tumor necrosis factor receptor: Fc fusion protein. N Engl J Med 334: 1697–1702

    Google Scholar 

  53. Echtenacher B, Falk W, Mannel D, Krammer PH (1990) Requirement of endogenous tumour necrosis factor/cachectin for recovery from experimental peritonitis. J Immunol 145: 3762–3766

    PubMed  CAS  Google Scholar 

  54. van der Meer JWM (1988) The effects of recombinant interleukin-1 and recombinant tumor necrosis factor on non-specific resistance to infection. Biotherapy 1: 19–25

    Article  PubMed  Google Scholar 

  55. Ronco C, Ricci Z, Bellomo R (2001) Importance of increased ultrafiltration volume and impact on mortality: sepsis and cytokine story and the role of continuous veno-venous hemofiltration. Curr Opin Nephrol Hypertens 10: 755–761

    Article  PubMed  CAS  Google Scholar 

  56. Silvester W (1997) Mediator removal with CRRT: complement and cytokines. Am J Kidney Dis 30 (suppl 4): 538 - S43

    Google Scholar 

  57. Hoffmann JN, Hartl WH, Deppisch R, et al (1995) Hemofiltration in human sepsis: evidence for elimination of immunomodulatory substances. Kidney Int 48: 1563–1570

    Article  PubMed  CAS  Google Scholar 

  58. Gasche Y, Pascual M, Suter PM, et al (1996) Complement depletion during haemofiltration with polyacilonitrile membranes. Nephrol Dial Transplant 11: 117–119

    Article  PubMed  CAS  Google Scholar 

  59. Goldfarb S, Golper TA (1994) Proinflammatory cytokines and hemofiltration membranes. J Am Soc Nephrol 5: 228–232

    PubMed  CAS  Google Scholar 

  60. Kellum JA, Johnson JP, Kramer D, et al (1998) Diffusive vs. convective therapy: effects on mediators of inflammation in patients with severe systemic inflammatory response syndrome. Crit Care Med 26: 1995–2000

    Article  PubMed  CAS  Google Scholar 

  61. Braun N, Giolai M, Rosenfeld S, et al (1993) Clearance of interleukin-6 during continuous veno-venous hemofiltration in patients with septic shock. A prospective, controlled clinical study. J Am Soc Nephrol 4: 336 (abst)

    Google Scholar 

  62. Mariano F, Tetta C, Guida GE, Triolo G, Camussi G (2001) Hemofiltration reduces the priming activity on neutrophil chemiluminescence in septic patients. Kidney Int 60: 1598–1605

    Article  PubMed  CAS  Google Scholar 

  63. Mariano F, Guida G, Donati D, et al (1999) Production of platelet-activating factor in patients with sepsis-associated acute renal failure. Nephrol Dial Transplant 14: 1150–1157

    Article  PubMed  CAS  Google Scholar 

  64. Sander A, Armbruster W, Sander B, et al (1997) Haemofiltration increases IL-6 clearance in early systemic inflammatory response syndrome but does not alter IL-6 and TNF alpha plasma concentrations. Intensive Care Med 23: 878–884

    Article  PubMed  CAS  Google Scholar 

  65. De Vriese AS, Colardyn FA, Philippe JJ, et al (1999) Cytokine removal during continuous hemofiltration in septic patients. J Am Soc Nephrol 10: 846–853

    PubMed  Google Scholar 

  66. Cole L, Bellomo R, Journois D, et al (2002) A phase II randomized, controlled trial of continuous hemofiltration in sepsis. Crit Care Med 30: 100–106

    Article  PubMed  CAS  Google Scholar 

  67. Heering P, Morgera S, Schmitz FJ, et al (1997) Cytokine removal and cardiovascular hemodynamics in septic patients with continuous venovenous hemofiltration. Intensive Care Med 23: 288–296

    Article  PubMed  CAS  Google Scholar 

  68. Ronco C, Brendolan A, Lonnemann G, et al (2002) A pilot study of coupled plasma filtration with adsorption in septic shock. Crit Care Med 30: 1250–1255

    Article  PubMed  Google Scholar 

  69. De Vriese AS, Vanholder RC, Pascual M, et al (1999) Can inflammatory cytokines be removed efficiently by continuous renal replacement therapies? Intensive Care Med 25: 903–910

    Article  PubMed  Google Scholar 

  70. Grootendorst AF, van Bommel EFH, van der Hoven B, et al (1992) High volume hemofiltration improves hemodynamics of endotoxin-induced shock in the pig. J Crit Care 7: 67–75

    Article  Google Scholar 

  71. Grootendorst AF, van Bommel EFH, van Leengoed LA, et al (1993) Infusion of ultrafiltrate from endotoxemic pigs depresses myocardial performance in normal pigs. J Crit Care 8: 161–169

    Article  PubMed  CAS  Google Scholar 

  72. Grootendorst AF, van Bommel EFH, van Leengoed LA, et al (1994) High volume hemofiltration improves hemodynamics and survival of pigs exposed to gut ischemia and reperfusion. Shock 2: 72–78

    Article  PubMed  CAS  Google Scholar 

  73. Lee PA, Matson JR, Pryor RW, Hinshaw LB (1993) Continuous arteriovenous hemofiltration therapy for Staphylococcus aureus-induced septicemia in immature swine. Crit Care Med 21: 914–924

    Article  PubMed  CAS  Google Scholar 

  74. Rogiers P, Zhang H, Smail N, et al (1999) Continuous venovenous hemofiltration improves cardiac performance by mechanisms other than tumor necrosis factor-alpha attenuation during endotoxic shock. Crit Care Med 27: 1848–1855

    Article  PubMed  CAS  Google Scholar 

  75. Yekebas EF, Eisenberger CF, Ohnesorge H, et al (2001) Attenuation of sepsis-related immunoparalysis by continuous veno-venous hemofiltration in experimental porcine pancreatitis. Grit Care Med 29: 1423–1430

    Article  CAS  Google Scholar 

  76. Nagashima M, Shin’oka T, Nollert G, et al (1998) High-volume continuous hemofiltration during cardiopulmonary bypass attenuates pulmonary dysfunction in neonatal lambs after deep hypothermic circulatory arrest. Circulation 98 (suppl 19):II378–384

    Google Scholar 

  77. Bellomo R, Kellum JA, Gandhi CR, Pinsky MR (2000) The effect of intensive plasma water exchange by hemofiltration on hemodynamics and soluble mediators in canine endotoxemia. Am J Respir Crit Care Med 161: 1429–1436

    Article  PubMed  CAS  Google Scholar 

  78. Ronco C, Bellomo R, Homel P, et al (2000) Effects of different doses in continuous veno-venous haemofiltration on outcomes of acute renal failure: a prospective randomised trial. Lancet 356: 26–30

    Article  PubMed  CAS  Google Scholar 

  79. Journois D, Israel Biet D, Pouard P, et al (1996) High-volume, zero-balanced hemofiltration to reduce delayed inflammatory response to cardiopulmonary bypass in children. Anesthesiology 85: 965–976

    Article  PubMed  CAS  Google Scholar 

  80. Oudemans-van Straaten HM, Bosman RJ, et al (1999) Outcome of critically ill patients treated with intermittent high-volume haemofiltration: a prospective cohort analysis. Intensive Care Med 25: 814–821

    Article  PubMed  Google Scholar 

  81. Cole L, Bellomo R, Journois D, et al (2001) High-volume hemofiltration in human septic shock. Intensive Care Med 27: 978–986

    Article  PubMed  CAS  Google Scholar 

  82. Honore PM, Jamez J, Wauthier M, et al (2000) Prospective evaluation of short-term, high-volume isovolemic hemofiltration on the hemodynamic course and outcome in patients with intractable circulatory failure resulting from septic shock. Crit Care Med 28: 3581–3587

    Article  PubMed  CAS  Google Scholar 

  83. Lee PA, Weger G, Pryor RW, Matson JR (1998) Effects of filter pore size on efficacy of continuous arteriovenous hemofiltration therapy for staphylococcus aureus-induced septicemia in immature swine. Crit Care Med 26: 730–737

    Article  PubMed  CAS  Google Scholar 

  84. Kline JA, Gordon BE, Williams C, et al (1999) Large-pore hemodialysis in acute endotoxin shock. Crit Care Med 27: 588–596

    Article  PubMed  CAS  Google Scholar 

  85. Morgera S, Buder W, Lehmann C, et al (2000) High cut off membrane haemofiltration in septic patients with multiorgan failure. A preliminary report. Blood Purif 18: 61 (abst)

    Google Scholar 

  86. Reeves JH, Butt WW, Shann F, et al and the Plasmafiltration in Sepsis Study Group (1999). Continuous plasmafiltration in sepsis syndrome. Crit Care Med 27: 2096–2104

    Google Scholar 

  87. Tetta C, Cavaillon JM, Schulze M, et al (1998) Removal of cytokines and activated complement components in an experimental model of continuous plasma filtration coupled with sorbent adsorption. Nephrol Dial Transplant 13: 1458–1464

    Article  PubMed  CAS  Google Scholar 

  88. Tetta C, Gianotti L, Cavaillon JM, et al (2000) Coupled plasma filtration-adsorption in a rabbit model of endotoxic shock. Crit Care Med 28: 1526–1533

    Article  PubMed  CAS  Google Scholar 

  89. Lonnemann G, Bechstein M, Linnenweber S, et al (1999) Tumor necrosis factor-alpha during continuous high-flux hemodialysis in sepsis with acute renal failure. Kidney Int Suppl 72: S84 - S87

    Article  PubMed  CAS  Google Scholar 

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Authors
  1. C. Tetta
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  2. R. Bellomo
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  3. C. Ronco
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Editors and Affiliations

  1. Department of Intensive Care, Erasme Hospital, Free University of Brussels, Route de Lennik 808, B-1070, Brussels, Belgium

    Jean-Louis Vincent MD, PhD, FCCM, FCCP (Head) (Head)

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Tetta, C., Bellomo, R., Ronco, C. (2003). Interpreting the Mechanisms of CRRT in Sepsis: The Peak Concentration Hypothesis. In: Vincent, JL. (eds) Intensive Care Medicine. Springer, New York, NY. https://doi.org/10.1007/978-1-4757-5548-0_62

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