Ronald E. Goans

Early dose assessment following severe radiation accidents

Early treatment of victims of high level acute whole-body x-ray or gamma exposure has been shown to improve their likelihood of survival. However, in such cases, both the magnitude of the exposure and the dosimetry profile(s) of the victim(s) are often not known in detail for days to weeks. A simple dose-prediction algorithm based on lymphocyte kinetics as documented in prior radiation accidents is presented here. This algorithm provides an estimate of dose within the first 8 h following an acute whole-body exposure. Early lymphocyte depletion kinetics after a severe radiation accident follow a single exponential, L(t) = L(o)e(-k(D¿t), where k(D) is a rate constant, dependent primarily on the average dose, D. Within the first 8 h post-accident, K(D) may be calculated utilizing serial lymphocyte counts. Data from the REAC/TS Radiation Accident Registry were used to develop a dose-prediction algorithm from 43 gamma exposure cases where both lymphocyte kinetics and dose reconstruction were felt to be reasonably reliable. The inverse relationship D(K) may be modeled by a simple two parameter curve of the form D = a/(1 + b/K) in the range 0 < or = D < or = 15 Gy, with fitting parameters (mean +/- SD): a = 13.6 +/- 1.7 Gy, and b = 1.0 +/- 0.20 d(-1). Dose estimated in this manner is intended to serve only as a first approximation to guide initial medical management.

Medical Management Of Radiological Casualties

Victims of radiological terrorism events require prompt diagnosis and treatment of medical and surgical conditions as well as conditions related to radiation exposure. Hospital emergency personnel should triage victims using traditional medical and trauma criteria. Radiation dose can be estimated early post-event using rapid-sort, automated biodosimetry and clinical parameters such as the clinical history, the time to emesis (TE), and lymphocyte depletion kinetics. For TE < 2 h, the effective whole-body dose is at least 3 Gy. If TE < 1 h, the whole-body dose most probably exceeds 4 Gy. Lymphocyte depletion follows dose-dependent, first order kinetics after high-level gamma and criticality incidents. Patient radiation dose can be estimated very effectively from the medical history, serial lymphocyte counts, and TE, and subsequently confirmed with chromosome-aberration bioassay, the current gold standard. These data are effectively analyzed using the Armed Forces Radiobiology Research Institute Biodosimetry Assessment Tool. The medical management of patients with acute, moderate to severe radiation exposure (effective whole-body dose >3 Gy) should emphasize the rapid administration of colony stimulating factors. All of these compounds decrease the duration of radiation-induced neutropenia and stimulate neutrophil recovery, albeit with some variability, in patients who have received myelotoxic chemotherapy, and all have demonstrated benefit in irradiated animals. For those patients developing febrile radiation-induced neutropenia, adherence to the current Infectious Diseases Society of America guidelines for high-risk neutropenia is recommended.

Early dose assessment in criticality accidents

Early estimation of dose is useful in the medical evaluation of severe radiation accidents. In a prior publication, lymphocyte depletion kinetics were shown to follow an exponential decline for gamma accidents in which the average whole-body dose was in the range 50 cGy < D < 8-10 Gy. In that study, the depletion rate constant was linearly related to dose, within the statistical variation of the historical hematological data. This simple technique has now been extended to include analysis of various types of criticality accidents (liquid process; water moderated systems; metallic systems). Lymphocyte depletion in high-level mixed gamma/neutron accidents is found to be approximately equal, at a given effective dose, to that for gamma accidents. This universality would indicate a neutron RBE for human lymphocytes close to unity. Furthermore, the technique appears to be insensitive to the shape of gamma and neutron spectra, therefore making it especially robust for initial, approximate dose estimation.

Synopsis of Partial-Body Radiation Diagnostic Biomarkers and Medical Management of Radiation Injury Workshop

Abstract Radiation exposures from accidents, nuclear detonations or terrorist incidents are unlikely to be homogeneous; however, current biodosimetric approaches are developed and validated primarily in whole-body irradiation models. A workshop was held at the Armed Forces Radiobiology Research Institute in May 2008 to draw attention to the need for partial-body biodosimetry, to discuss current knowledge, and to identify the gaps to be filled. A panel of international experts and the workshop attendees discussed the requirements and concepts for a path forward. This report addresses eight key areas identified by the Workshop Program Committee for future focus: (1) improved cytogenetics, (2) clinical signs and symptoms, (3) cutaneous bioindicators, (4) organ-specific biomarkers, (5) biophysical markers of dose, (6) integrated diagnostic approaches, (7) confounding factors, and (8) requirements for post-event medical follow-up. For each area, the status, advantages and limitations of existing approaches and suggestions for new directions are presented.

Management of Ionizing Radiation Injuries and Illnesses, Part 4: Acute Radiation Syndrome

To provide proper medical care for patients after a radiation incident, it is necessary to make the correct diagnosis in a timely manner and to ascertain the relative magnitude of the incident. The present article addresses the clinical diagnosis and management of high-dose radiation injuries and illnesses in the first 24 to 72 hours after a radiologic or nuclear incident. To evaluate the magnitude of a high-dose incident, it is important for the health physicist, physician, and radiobiologist to work together and to assess many variables, including medical history and physical examination results; the timing of prodromal signs and symptoms (eg, nausea, vomiting, diarrhea, transient incapacitation, hypotension, and other signs and symptoms suggestive of high-level exposure); and the incident history, including system geometry, source-patient distance, and the suspected radiation dose distribution.

Rapid internal dose magnitude estimation in emergency situations using annual limits on intake (ALI) comparisons.

It is crucial to integrate health physics into the medical management of radiation illness or injury. The key to early medical management is not necessarily radiation dose calculation and assignment, but radiation dose magnitude estimation. The magnitude of the dose can be used to predict potential biological consequences and the corresponding need for medical intervention. It is, therefore, imperative that physicians and health physicists have the necessary tools to help guide this decision making process. All internal radiation doses should be assigned using proper dosimetry techniques, but the formal internal dosimetry process often takes time that may delay treatment, thus reducing the efficacy of some medical countermeasures. Magnitudes of inhalation or ingestion intakes or intakes associated with contaminated wounds can be estimated by applying simple rules of thumb to sample results or direct measurements and comparing the outcome to known limits for a projection of dose magnitude. Although a United States regulatory unit, the annual limit on intake (ALI) is based on committed dose, and can therefore be used as a comparison point. For example, internal dose magnitudes associated with contaminated wounds can be estimated by comparing a direct wound measurement taken soon after the injury to the product of the ingestion ALI and the associated f1 value (the fractional uptake from the small intestine to the blood). International Commission on Radiation Protection Publication 96, as well as other resources, recommends treatment based on ALI determination. Often, treatment decisions have to be made with limited information. However, one can still perform dose magnitude estimations in order to help effectively guide the need for medical treatment by properly assessing the situation and appropriately applying basic rules of thumb.

Clinical application of the AFRRI BAT computer program.

The Biodosimetry Assessment Tool (BAT) is a computer program developed by the Armed Forces Radiobiology Research Institute (AFRRI) as an aid to provide early diagnostic information (clinical signs and symptoms, physical dosimetry, etc.) to health care providers responsible for the initial management of radiation casualties after a major radiation incident. It is designed primarily to permit collection, integration, and archiving of data obtained from patients accidentally exposed to ionizing radiation. BAT also provides an early estimate of radiation dose using the timing of prodromal symptoms, clinical data, and various aspects of the time-dependent hematology profile. Collection of relevant data is facilitated by use of structured templates and user-friendly software. The BAT software is illustrated here using five historical cases from the U.S. Radiation Accident Registry maintained by the Radiation Emergency Assistance Center/Training Site (REAC/TS) for the U.S. Department of Energy.

Case Report: Industrial X-Ray Injury Treated With Non-Cultured Autologous Adipose-Derived Stromal Vascular Fraction (SVF).

Abstract Local cutaneous injuries induced by ionizing radiation (IR) are difficult to treat. Many have reported local injection of adipose-derived stromal vascular fraction (SVF), often with additional therapies, as an effective treatment of IR-induced injury even after other local therapies have failed. The authors report a case of a locally recurrent, IR-induced wound that was treated with autologous, non-cultured SVF without other concurrent therapy. A nondestructive testing technician was exposed to 130 kVp x rays to his non-dominant right thumb on 5 October 2011. The wound healed 4 mo after initial conservative therapy with oral/topical &agr;-tocopherol, oral pentoxifylline, naproxen sodium, low-dose oral steroids, topical steroids, hyperbaric oxygen therapy (HBOT), oral antihistamines, and topical aloe vera. Remission lasted approximately 17 mo with one minor relapse in July 2012 after minimal trauma and subsequent healing. Aggressive wound breakdown during June 2013 required additional therapy with HBOT. An erythematous, annular papule developed over the following 12 mo (during which time the patient was not undergoing prescribed treatment). Electron paramagnetic resonance (EPR) done more than 2 mo after exposure to IR revealed dose estimates of 14 ± 3 Gy and 19 ± 6 Gy from two centers using different EPR techniques. The patient underwent debridement of the 0.5 cm papular area, followed by SVF injection into and around the wound bed and throughout the thumb without complication. Eleven months post SVF injection, the patient has been essentially asymptomatic with an intact integument. These results raise the possibility of prolonged benefit from SVF therapy without the use of cytokines. Since there is currently no consensus on the use of isolated SVF therapy in chronic, local IR-induced injury, assessment of this approach in an appropriately powered, controlled trial in experimental animals with local radiation injury appears to be indicated.

Appearance of pseudo-Pelger Huet anomaly after accidental exposure to ionizing radiation in vivo.

AbstractTo evaluate the morphology of formed elements of human blood after exposure to ionizing radiation in vivo, archival smears of peripheral blood from eight individuals involved in the 1958 Y‐12 criticality accident at Oak Ridge, Tennessee, were examined manually by light microscopy. For each case, increased interlobar bridging was observed in nuclei of the myeloid cells, many of which were bilobed and morphologically similar to Pelger Huet (PH) cells. The high-dose group (n = 5, 2.98–4.61 Gy-Eq) exhibited 13.0 ± 0.85% PH cells (mean ± SEM) in the neutrophil population compared to 6.8 ± 1.6% in the low-dose group (n = 3, 0.29–0.86 Gy-Eq; p = 0.008). An age- and gender-matched control group (n = 8) exhibited 3.6 ± 0.9% PH cells. Results of a one-way ANOVA show that the high-dose group is statistically different from both the low-dose group and the control group (p = 0.002). However, the low-dose group is not statistically different from the control group (p = 0.122). The mean number of nuclear lobes in blood neutrophils was also enumerated as a function of time after exposure and was found to be diminished, consistent with incomplete nuclear segmentation that is characteristic of the Pelger Huet anomaly (PHA). In contrast to these changes in myeloid cells, the morphology of erythrocytes and platelets appeared to be normal. The authors conclude that ionizing radiation induces abnormal morphology of circulating neutrophils, which is similar to the pseudo-PHA that is acquired in disorders such as myelodysplastic syndrome, acute myeloid leukemia, and leukemoid reactions. Potential molecular mechanisms by which radiation induces this morphological change are discussed. From this cohort, the biomarker appears to be present early post-accident (<9 h) and stable at least up to 16 y post-accident. Assessment of circulating pseudo-Pelger Huet cells is being investigated as a potential biodosimetric tool.

Management of Ionizing Radiation Injuries and Illnesses, Part 5: Local Radiation Injury

This final article in the series on the medical management of ionizing radiation injuries and illnesses focuses on the effects of acute ionizing radiation exposure to one of the largest organ systems of the body-the skin. These injuries may extend beyond the skin into deeper tissues and cause local radiation injury. There are numerous causes of these injuries, ranging from industrial incidents to medical procedures. In the present article, the authors characterize the clinical course, pathophysiologic process, sources of injury, diagnosis, and management of local radiation injury and describe a clinical scenario. This information is important for primary care physicians, to whom patients are likely to initially present with such injuries.