Radiological Casualties Research Articles

Pediatric Medical Countermeasures: Antidotes and Cytokines for Radiological and Nuclear Incidents and Terrorism.

The war in Ukraine raises concerns for potential hazards of radiological and nuclear incidents. Children are particularly vulnerable in these incidents and may need pharmaceutical countermeasures, including antidotes and cytokines. Searches found no published study comparing pediatric indications and dosing among standard references detailing pediatric medications for these incidents. This study addresses this gap by collecting, tabulating, and disseminating this information to healthcare professionals caring for children. Expert consensus chose the following references to compare their pediatric indications and dosing of medical countermeasures for radiation exposure and internal contamination with radioactive materials: Advanced Hazmat Life Support (AHLS) for Radiological Incidents and Terrorism, DailyMed, Internal Contamination Clinical Reference, Medical Aspects of Radiation Incidents, and Medical Management of Radiological Casualties, as well as Micromedex, POISINDEX, and Radiation Emergency Medical Management (REMM). This is the first study comparing pediatric indications and dosing for medical countermeasures among commonly used references for radiological and nuclear incidents.

Radiation Injury Treatment Network®

This article provides an overview of Radiation Injury Treatment Network® (RITN), its preparedness activities and capabilities, including training and educating over 11,500 hospital staff, coordinating over 500 exercises, developing treatment guidelines, developing standard operating procedures, and being recognized by the U.S. federal government as a national response asset. The RITN provides comprehensive evaluation and treatment for victims with marrow toxic injuries. Many of the casualties from the detonation of an improvised nuclear device (IND) (a.k.a. terrorist nuclear bomb) with only radiation injuries will be salvageable; however, they would require outpatient and/or inpatient care. Recognizing this, the U.S. National Marrow Donor Program (NMDP), U.S. Navy, and American Society for Blood and Marrow Transplantation (ASBMT) collaboratively developed RITN, which comprises medical centers with expertise in the management of bone marrow failure. The medical community will undoubtedly be taxed by the resulting medical surge from an IND despite the well-defined United States emergency medical system, the National Disaster Medical System; however, one area that is unique for radiological disasters is the care for casualties with acute radiation syndrome. Hematologists and oncologists purposefully expose their cancer patients to high doses of radiation and toxic chemicals for chemotherapy as they treat their patients, resulting in symptoms not unlike casualties with exposure to ionizing radiation from a radiological disaster. This makes the staff from cancer centers ideal for the specialized care that will be required for thousands of casualties following a mass casualty radiological incident. The RITN is a model for how a collaborative effort can fill a readiness gap-through its network of 76 hospitals, blood donor centers, and cord blood banks, the RITN is preparing to provide outpatient care and specialized supportive care to up to 63,000 radiological casualties.

Radiation Dose-Rate Effects on Gene Expression in a Mouse Biodosimetry Model.

In the event of a nuclear accident or radiological terrorist attack, there will be a pressing need for biodosimetry to triage a large, potentially exposed population and to assign individuals to appropriate treatment. Exposures from fallout are likely, resulting in protracted dose delivery that would, in turn, impact the extent of injury. Biodosimetry approaches that can distinguish such low-dose-rate (LDR) exposures from acute exposures have not yet been developed. In this study, we used the C57BL/6 mouse model in an initial investigation of the impact of low-dose-rate delivery on the transcriptomic response in blood. While a large number of the same genes responded to LDR and acute radiation exposures, for many genes the magnitude of response was lower after LDR exposures. Some genes, however, were differentially expressed (P < 0.001, false discovery rate <5%) in mice exposed to LDR compared with mice exposed to acute radiation. We identified a set of 164 genes that correctly classified 97% of the samples in this experiment as exposed to acute or LDR radiation using a support vector machine algorithm. Gene expression is a promising approach to radiation biodosimetry, enhanced greatly by this first demonstration of its potential for distinguishing between acute and LDR exposures. Further development of this aspect of radiation biodosimetry, either as part of a complete gene expression biodosimetry test or as an adjunct to other methods, could provide vital triage information in a mass radiological casualty event.

Circulating Interleukin-18 as a Biomarker of Total-Body Radiation Exposure in Mice, Minipigs, and Nonhuman Primates (NHP)

We aim to develop a rapid, easy-to-use, inexpensive and accurate radiation dose-assessment assay that tests easily obtained samples (e.g., blood) to triage and track radiological casualties, and to evaluate the radioprotective and therapeutic effects of radiation countermeasures. In the present study, we evaluated the interleukin (IL)-1 family of cytokines, IL-1β, IL-18 and IL-33, as well as their secondary cytokines’ expression and secretion in CD2F1 mouse bone marrow (BM), spleen, thymus and serum in response to γ-radiation from sublethal to lethal doses (5, 7, 8, 9, 10, or 12 Gy) at different time points using the enzyme-linked immune sorbent assay (ELISA), immunoblotting, and cytokine antibody array. Our data identified increases of IL-1β, IL-18, and/or IL-33 in mouse thymus, spleen and BM cells after total-body irradiation (TBI). However, levels of these cytokines varied in different tissues. Interestingly, IL-18 but not IL-1β or IL-33 increased significantly (2.5–24 fold) and stably in mouse serum from day 1 after TBI up to 13 days in a radiation dose-dependent manner. We further confirmed our finding in total-body γ-irradiated nonhuman primates (NHPs) and minipigs, and demonstrated that radiation significantly enhanced IL-18 in serum from NHPs 2–4 days post-irradiation and in minipig plasma 1–3 days post-irradiation. Finally, we compared circulating IL-18 with the well known hematological radiation biomarkers lymphocyte and neutrophil counts in blood of mouse, minipigs and NHPs and demonstrated close correlations between these biomarkers in response to radiation. Our results suggest that the elevated levels of circulating IL-18 after radiation proportionally reflect radiation dose and severity of radiation injury and may be used both as a potential biomarker for triage and also to track casualties after radiological accidents as well as for therapeutic radiation exposure.

Inter- and intra-laboratory comparison of a multibiodosimetric approach to triage in a simulated, large scale radiation emergency

Purpose: The European Union's Seventh Framework Programme-funded project ‘Multi-disciplinary biodosimetric tools to manage high scale radiological casualties’ (MULTIBIODOSE) has developed a multiparametric approach to radiation biodosimetry, with a particular emphasis on triage of large numbers of potentially exposed individuals following accidental exposures. In November 2012, an emergency exercise took place which tested the capabilities of the MULTIBIODOSE project partners. The exercise described here had a dual purpose: Intercomparison of (i) three biodosimetric assays, and (ii) the capabilities of the seven laboratories, with regards to provision of triage status for suspected radiation exposed individuals.Materials and methods: Three biological dosimetry tools – the dicentric, micronucleus and gamma-H2AX (the phosphorylated form of member X of histone H2A, in response to DNA double-strand breaks) foci assays – were tested, in addition to provision of the triage status results (low exposure: < 1 Gy; medium exposure: 1–2 Gy; high exposure: > 2 Gy) by the MULTIBIODOSE software. The exercise was run in two modes: An initial triage categorisation of samples (based on the first dose estimates for each assay received from each laboratory) followed by collation of the full set of estimated doses (all the results from all modes of each assay carried out by the participating laboratories) calculated using as many modes of operation as possible of the different assays developed during the project. Simulated acute whole body and partial body exposures were included.Results: The results of the initial triage categorisation and the full comparison of assays and methods within and between laboratories are presented here.Conclusions: The data demonstrate that the MULTIBIODOSE approach of applying multiparametric tools to radiation emergencies is valid and effective.

Biological dosimetry for triage of casualties in a large-scale radiological emergency:capacity of the EU member states

In recent years, a number of events have occurred that highlight the necessity of being prepared for a possible large-scale radiological event. An important question is how well are European Union (EU) Member States prepared to cope with mass radiological casualties. A survey to establish the current status of biological dosimetry across the EU was carried out with the aim of assessing capacity to perform biodosimetric triage of accident victims. Information was sought from the radiation protection authorities of the 27 Member States plus Switzerland and Norway. Biology dosimetry is established in 15 EU countries. Their total capacity for dosimetric triage is about 1500 cases per week analysed with a dicentric assay or about 800 cases analysed with a micronucleus assay. Although these numbers appear encouraging, there is not much collaboration between the laboratories and what is required is a network at the EU level.

Acute Heart Failure Syndromes, CT Radiation, and Radiological Casualties

Acute Heart Failure Syndromes, CT Radiation, and Radiological Casualties

Amylase and blood cell-count hematological radiation-injury biomarkers in a rhesus monkey radiation model—use of multiparameter and integrated biological dosimetry

Effective medical management of suspected radiation exposure incidents requires the recording of dynamic medical data (clinical signs and symptoms), biological assessments of radiation exposure, and physical dosimetry in order to provide diagnostic information to the treating physician and dose assessment for personnel radiation protection records. The need to rapidly assess radiation dose in mass-casualty and population-monitoring scenarios prompted an evaluation of suitable biomarkers that can provide early diagnostic information after exposure. We investigated the utility of serum amylase and hematological blood-cell count biomarkers to provide early assessment of severe radiation exposures in a non-human primate model (i.e., rhesus macaques; n = 8 ) exposed to whole-body radiation of Co 60 -gamma rays (6.5 Gy, 40 cGy min - 1 ). Serum amylase activity was significantly elevated ( 12.3 ± 3.27 - and 2.6 ± 0.058 -fold of day zero samples) at 1 and 2-days, respectively, after radiation. Lymphocyte cell counts decreased ( ⩽ 15 % of day zero samples) 1 and 2 days after radiation exposure. Neutrophil cell counts increased at day one by 1.9 ( ± 0.38 ) -fold compared with levels before irradiation. The ratios of neutrophil to lymphocyte cell counts increased by 13 ( ± 2.66 ) - and 4.23 ( ± 0.95 ) -fold at 1 and 2 days, respectively, after irradiation. These results demonstrate that increases in serum amylase activity along with decreases of lymphocyte counts, increases in neutrophil cell counts, and increases in the ratio of neutrophil to lymphocyte counts 1 day after irradiation can provide enhanced early triage discrimination of individuals with severe radiation exposure and injury. Use of the biodosimetry assessment tool (BAT) application is encouraged to permit dynamic recording of medical data in the management of a suspected radiological casualty.

Use High Awareness and Judgment to Screen Emergency Department Patients for Radiation Exposure

Use High Awareness and Judgment to Screen Emergency Department Patients for Radiation Exposure

The Mosquito Hypothetically Considered as the Agent of Transmission of Yellow Fever

The probability of nuclear war is deemed small. A large-scale release of radionuclides into a populated area is considered much more likely. Treatment of radiological casualties is possible even after a detonation that immediately overwhelms surviving local resources. Care would be required at medical centers throughout the country. For those radiological casualties where treatment is most likely to make the difference between survival and death, a window of several days exists in which patients can be identified, dispersed, and therapy initiated. Most deaths due to radiation occur as a result of bone marrow damage and secondary infection. Treatment is based on stimulation of the surviving bone marrow stem cells and protection from infection. With aggressive treatment of immunosuppression, very few deaths should be anticipated at radiation doses of less than 5 Gy. Only those patients who exhibit signs of neurological damage should be considered expectant. All other casualties are candidates for therapy.