Multi-organ Injury, Multi-organ Dysfunction Syndrome, Multi-organ Failure: A New Hypothesis of Whole Body Radiation Effects

• Acute Radiation Syndrome: the traditional view of radiation injury
  • Features 4 predominant acute subsyndromes
    • Hematopoietic
    • Gastrointestinal
    • Cutaneous
    • Neurovascular
  • Traditionally thought to represent the most prominent effects of significant doses of whole body radiation
  • These subsyndromes form the basis of the European METREPOL concept of diagnosis and triage of radiation injury.²
    (See Manage Subsyndromes of Acute Radiation Syndrome).
  • The METREPOL system is being extensively revised, as new concepts of radiation injury become better understood, as noted below.
• MOI, MODS, MOF: the hypothesis about radiation injury
  • European researchers have recently proposed a new concept of radiation pathophysiology which is a clinical continuum of
    • Multi-organ Injury (MOI)
    • Multi-organ Dysfunction Syndrome (MODS)
    • Multi-organ Failure (MOF), which is irreversible
  • Features of this new concept include
    • Systemic effects which are not limited to the 4 organ subsyndromes noted above
    • Marked involvement of lung, kidney, liver and other organs in addition to those in the ARS subsyndromes, seen particularly at the higher doses
    • Inflammation as a prominent feature of early radiation injury, although the role of anti-inflammatory treatment is unknown and could be detrimental (i.e., use of corticosteroids in the face of immunosuppression)
  • Key descriptions and references about MOI, MOF, MODS are in
    • Fliedner TM, Dorr HD, Meineke V. Multi-organ involvement as a pathogenetic principle of the radiation syndromes: a study involving 110 case histories document in SEARCH and classified as the bases of haematopoietic indicators of effect. BJR Suppl. 2005;27:1-8.
    • Bertho JM, Roy L, Souidi M, Benderitter M, Gueguen Y, Lataillade JJ, Prat M, Fagot T, De Revel T, Gourmelon P, New biological indicators to evaluate and monitor radiation-induced damage: an accident case report. Radiat Res. 2008 May;169(5):543-50. [PubMed Citation]

References:

1. MacVittie TJ, Farese AM, Kane MA. ARS, DEARE, and Multiple-organ Injury: A Strategic and Tactical Approach to Link Radiation Effects, Animal Models, Medical Countermeasures, and Biomarker Development to Predict Clinical Outcome. Health Phys. 2019 Apr;116(4):453. [PubMed Citation]
2. Fliedner TM, Friesecke I, Beyrer K. Medical Management of Radiation Accidents: Manual on the Acute Radiation Syndrome. (METREPOL) (PDF - 970 KB) (originally published by Oxford: British Institute of Radiology; 2001) Compendium to the main METREPOL document (PDF - 580 KB)
3. Radiation-Induced Multi-Organ Involvement and Failure: A Challenge for Pathogenetic, Diagnostic and Therapeutic Approaches and Research, BJR Suppl. 2005;27:1-200. (Entire issue devoted to multi-organ involvement.)
4. Chapel A, Bertho JM, Bensidhoum M, Fouillard L, Young RG, Frick J, Demarquay C, Cuvelier F, Mathieu E, Trompier F, Dudoignon N, Germain C, Mazurier C, Aigueperse J, Borneman J, Gorin NC, Gourmelon P, Thierry D. Mesenchymal stem cells home to injured tissues when co-infused with hematopoietic cells to treat a radiation-induced multi-organ failure syndrome. J Gene Med. 2003 Dec;5(12):1028-38. [PubMed Citation]
5. Pu X, Ma S, Gao Y, Xu T, Chang P, Dong L. Mesenchymal Stem Cell-Derived Exosomes: Biological Function and Their Therapeutic Potential in Radiation Damage. Cells. 2020 Dec 30;10(1):42. [PubMed Citation]

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