Immune Dysfunction from Radiation Exposure.

The hematopoietic system is highly sensitive to ionizing radiation. Damage to the immune system may result in opportunistic infections and hemorrhage, which could lead to mortality. Inflammation triggered by tissue damage can also lead to additional local or widespread tissue damage. The immune system is responsible for tissue repair and restoration, which is made more challenging when it is in the process of self-recovery. Because of these challenges, the Radiation and Nuclear Countermeasures Program (RNCP) and the Basic Immunology Branch (BIB) under the Division of Allergy, Immunology, and Transplantation (DAIT) within the National Institute of Allergy and Infectious Diseases (NIAID), along with partners from the Biomedical Advanced Research and Development Authority (BARDA), and the Radiation Injury Treatment Network (RITN) sponsored a two-day meeting titled Immune Dysfunction from Radiation Exposure held on September 9-10, 2020. The intent was to discuss the manifestations and mechanisms of radiation-induced immune dysfunction in people and animals, identify knowledge gaps, and discuss possible treatments to restore immune function and enhance tissue repair after irradiation.

Radiation Injury Treatment Network Medical and Nursing Workforce Radiation: Knowledge and Attitude Assessment.

OBJECTIVES: The Radiation Injury Treatment Network (RITN) is prepared to respond to a national disaster resulting in mass casualties with marrow toxic injuries. How effective existing RITN workforce education and training is, or whether health-care providers (HCPs) at these centers possess the knowledge and skills to care for patients following a radiation emergency is unclear. HCP knowledge regarding the medical effects and medical management of radiation-exposed patients, along with clinical competence and willingness to care for patients following a radiation emergency was assessed. METHODS: An online survey was conducted to assess level of knowledge regarding the medical effects of radiation, medical/nursing management of patients, self-perception of clinical competence, and willingness to respond to radiation emergencies and nuclear events. RESULTS: Attendance at previous radiation emergency management courses and overall knowledge scores were low for all respondents. The majority indicated they were willing to respond to a radiation event, but few believed they were clinically competent to do so. CONCLUSIONS: Despite willingness to respond, HCPs at RITN centers may not possess adequate knowledge of medical management of radiation patients, and appropriate response actions during a radiation emergency. RITN should increase the awareness of the importance of radiation education and training.

Chemical, Biological, Radiological, Nuclear, and Explosive (CBRNE) Science and the CBRNE Science Medical Operations Science Support Expert (CMOSSE).

A national need is to prepare for and respond to accidental or intentional disasters categorized as chemical, biological, radiological, nuclear, or explosive (CBRNE). These incidents require specific subject-matter expertise, yet have commonalities. We identify 7 core elements comprising CBRNE science that require integration for effective preparedness planning and public health and medical response and recovery. These core elements are (1) basic and clinical sciences, (2) modeling and systems management, (3) planning, (4) response and incident management, (5) recovery and resilience, (6) lessons learned, and (7) continuous improvement. A key feature is the ability of relevant subject matter experts to integrate information into response operations. We propose the CBRNE medical operations science support expert as a professional who (1) understands that CBRNE incidents require an integrated systems approach, (2) understands the key functions and contributions of CBRNE science practitioners, (3) helps direct strategic and tactical CBRNE planning and responses through first-hand experience, and (4) provides advice to senior decision-makers managing response activities. Recognition of both CBRNE science as a distinct competency and the establishment of the CBRNE medical operations science support expert informs the public of the enormous progress made, broadcasts opportunities for new talent, and enhances the sophistication and analytic expertise of senior managers planning for and responding to CBRNE incidents.

Use of Growth Factors and Cytokines to Treat Injuries Resulting from a Radiation Public Health Emergency.

In response to concerns over possible radiological or nuclear incidents, the Radiation and Nuclear Countermeasures Program within the National Institute of Allergy and Infectious Diseases (NIAID) was tasked by the U.S. Department of Health and Human Services to support development of medical countermeasures (MCM) to treat the acute and delayed injuries that can result from radiation exposure. To date, the only three drugs approved by the U.S. Food and Drug Administration for treatment of acute radiation syndrome are growth factors targeting granulocyte (Neupogen® or Neulasta®) or granulocyte and macrophage (Leukine®) hematopoietic cell lineages. Although these are currently stockpiled for deployment in response to a mass casualty scenario, these growth factors will likely be administered in a scarce-resources environment and availability may be limited. Therefore, there is growing interest in understanding the role that these growth factors play in mitigating radiation damage, to optimize their use and maximize the number of people who can be treated. For these reasons, the NIAID and the Radiation Injury Treatment Network organized a workshop to explore the use of growth factors and other cytokines as MCMs in the treatment of radiation-induced injuries. Subject matter experts from government, industry and academia gathered at this workshop to discuss the concept of operations, triage and treatment, administration to diverse civilian populations, growth factors under development for radiation indications, and how the practice of medicine can inform other potential approaches.

Use of Growth Factors and Other Cytokines for Treatment of Injuries During a Radiation Public Health Emergency.

Due to the threat of a radiological or nuclear incident that could impact citizens, the U.S. Department of Health and Human Services tasked the National Institute of Allergy and Infectious Diseases (NIAID) with identifying and funding early- to mid-stage medical countermeasure (MCM) development to treat radiation-induced injuries. Given that the body's natural response to radiation exposure includes production of growth factors and cytokines, and that the only drugs approved by the U.S. Food and Drug Administration to treat acute radiation syndrome are growth factors targeting either the granulocyte (Neupogen® or Neulasta®) or granulocyte and macrophage (Leukine®) hematopoietic cell lineages, there is interest in understanding the role that these factors play in responding to and/or ameliorating radiation damage. Furthermore, in an environment where resources are scarce, such as what might be expected during a radiation public health emergency, availability of growth factor or other treatments may be limited. For these reasons, the NIAID partnered with the Radiation Injury Treatment Network (RITN), whose membership includes medical centers with expertise in the management of bone marrow failure, to explore the use of growth factors and other cytokines as MCMs to mitigate/treat radiation injuries. A workshop was convened that included government, industry and academic subject matter experts, with presentations covering the anticipated concept of operations during a mass casualty incident including triage and treatment, growth factors under development for a radiation indication, and how the practice of medicine can inform other potential approaches, as well as considerations for administration of these products to diverse civilian populations. This report reviews the information presented, and provides an overview of the discussions from a guided breakout session.

Guidance, Training and Exercises for Responding to an Improvised Nuclear Device: First Receivers, Public Health.

All large-scale emergencies and disaster incidents, including the detonation of an improvised nuclear device (IND), have life and death medical consequences. Responders must have realistic plans to save lives and reduce physical and psychological morbidity. Fifteen years after 9/11, considerable progress toward developing and implementing such plans has been made, but gaps in the management of response to an IND loom large. Another paper in this series reviewed gaps for first responders; this paper reviews gaps for first receivers and public health. Closing gaps requires the implementation of complex systems including.

10 Years of Preparedness by the Radiation Injury Treatment Network.

The Radiation Injury Treatment Network (RITN) began in 2006 with the ambitious vision to provide a resource to help with the surge of casualties following a mass casualty incident with marrow toxic injuries. Through the efforts of the National Marrow Donor Program and American Society for Blood and Marrow Transplantation with the support of the Office of Naval Research, the initial 13 hospitals and cancer centers have grown to 76, training over 13,500 hospital staff and conducted, funded, and supported 580 disaster exercises testing preparedness. After a decade, there is more to do, but much laudatory work has been accomplished.

Radiation Injury Treatment Network®: Preparedness Through a Coalition of Cancer Centers.

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.

Public health and medical preparedness for a nuclear detonation: the nuclear incident medical enterprise.

Resilience and the ability to mitigate the consequences of a nuclear incident are enhanced by (1) effective planning, preparation and training; (2) ongoing interaction, formal exercises, and evaluation among the sectors involved; (3) effective and timely response and communication; and (4) continuous improvements based on new science, technology, experience, and ideas. Public health and medical planning require a complex, multi-faceted systematic approach involving federal, state, local, tribal, and territorial governments; private sector organizations; academia; industry; international partners; and individual experts and volunteers. The approach developed by the U.S. Department of Health and Human Services Nuclear Incident Medical Enterprise (NIME) is the result of efforts from government and nongovernment experts. It is a "bottom-up" systematic approach built on the available and emerging science that considers physical infrastructure damage, the spectrum of injuries, a scarce resources setting, the need for decision making in the face of a rapidly evolving situation with limited information early on, timely communication, and the need for tools and just-in-time information for responders who will likely be unfamiliar with radiation medicine and uncertain and overwhelmed in the face of the large number of casualties and the presence of radioactivity. The components of NIME can be used to support planning for, response to, and recovery from the effects of a nuclear incident. Recognizing that it is a continuous work-in-progress, the current status of the public health and medical preparedness and response for a nuclear incident is provided.

Medical planning and response for a nuclear detonation: a practical guide.

This article summarizes major points from a newly released guide published online by the Office of the Assistant Secretary for Preparedness and Response (ASPR). The article reviews basic principles about radiation and its measurement, short-term and long-term effects of radiation, and medical countermeasures as well as essential information about how to prepare for and respond to a nuclear detonation. A link is provided to the manual itself, which in turn is heavily referenced for readers who wish to have more detail.

World marrow donor association crisis response, business continuity, and disaster recovery guidelines.

Multiple institutions, such as donor registries, donor centers, transplantation centers, collection centers, and courier companies, are involved in the international exchange of hematopoietic stem cells. The ability to safely and efficiently ensure continued operation of a donor registry relies on an organization's resiliency in the face of an incident that could impede donor search, donor selection, stem cell collection, or transportation. The Quality Assurance Working Group of the World Marrow Donor Association has developed guidelines on how to establish an organizational resiliency program intended for donor registries initiating an emergency preparedness process. These guidelines cover the minimal requirements of preparedness in prevention and mitigation, crisis response, business continuity, and disaster recovery, and the need for continued maintenance and revision. Issues of international cooperation are addressed as well.

Radiation disasters: role of the BMT team.

Bone marrow transplant (BMT) teams do not generally consider themselves to be emergency responders. But the bone marrow is the most radiosensitive organ in the body, and early changes in peripheral blood counts remain the best indicator of major total-body radiation exposures. Following a mass casualty incident, such as that occasioned by a nuclear detonation, BMT teams should expect that they will be called upon for their expertise in managing severe myelosuppression. Numerous resources, including the Radiation Injury Treatment Network, are available to assist BMT teams in planning for such a role.

Radiation injury treatment network (RITN): healthcare professionals preparing for a mass casualty radiological or nuclear incident.

PURPOSE: To describe the history, composition, and activities of the Radiation Injury Treatment Network (RITN). The Radiation Injury Treatment Network® is a cooperative effort of the National Marrow Donor Program and the American Society for Blood and Marrow Transplantation. The goals of RITN are to educate hematologists, oncologists, and stem cell transplant practitioners about their potential involvement in the response to a radiation incident and provide treatment expertise. Injuries to the marrow system readily occur when a victim is exposed to ionising radiation. This focus therefore leverages the expertise of these specialists who are accustomed to providing the intensive supportive care required by patients with a suppressed marrow function. Following a radiological incident, RITN centres may be asked to: Accept patient transfers to their institutions; provide treatment expertise to practitioners caring for victims at other centres; travel to other centres to provide medical expertise; or provide data on victims treated at their centres. Moving forward, it is crucial that we develop a coordinated interdisciplinary approach in planning for and responding to radiological and nuclear incidents. The ongoing efforts of radiation biologists, radiation oncologists, and health physicists can and should complement the efforts of RITN and government agencies. CONCLUSION: RITN serves as a vital partner in preparedness and response efforts for potential radiological and nuclear incidents.

Medical management of radiation victims in the United States.

Many governmental and non-governmental agencies are involved in the planning for radiation events in the U.S. We will focus on medical management after mass casualty events, specifically the involvement of the Radiation Injury Treatment Network (RITN), a voluntary consortium of medical centers across the continental U.S. RITN and its partners have established standardized approaches for the evaluation and treatment of radiation victims, which are now available online. Efforts are underway to streamline these processes, provide training to healthcare practitioners around the country, and harmonize with similar efforts around the world.

Assessing surge capacity for radiation victims with marrow toxicity.

Hematologists/oncologists would provide essential care for victims of a catastrophic radiation incident, such as the detonation of an improvised nuclear device (IND). The US Radiation Injury Treatment Network (RITN) is a voluntary consortium of 37 academic medical centers, 8 blood donor centers, and 7 umbilical cord banks focused on preparedness for radiation incidents. The RITN conducted 2 tabletop exercises to evaluate response capability after a hypothetical IND detonation in a U.S. city. In the 2008 exercise, medical centers voluntarily accepted 1757 victims at their institutions, a small fraction of the number in need. In the 2009 exercise, each center was required to accept 300 victims. In response, the centers outlined multiple strategies to increase bed availability, extend staff and resources, and support family and friends accompanying transferred victims. The exercises highlighted shortcomings in current planning and future steps for improving surge capacity that are applicable to various mass casualty scenarios.

Stem cells, multiorgan failure in radiation emergency medical preparedness: a U.S./European Consultation Workshop.

The concern of the public regarding terrorist actions involving nuclear emergencies resulted in the reopening of the discussion regarding the best ways to cope with the inevitable health impairments. Medical experts from the US and from Europe considered it of importance to harmonize at an international level the diagnostic and therapeutic approaches regarding the radiation-induced health impairments. The present contribution is the result of the first U.S./European Consultation Workshop addressing approaches to radiation emergency preparedness and assistance, which was held recently at Ulm University, Ulm, Germany. Discussions dealt with the assessment of the extent of damage after total body exposure and, in particular, the quantity and quality of the damage to the hematopoietic stem cell pool. Secondly, the pathogenesis of the multiorgan failure was considered because of the organ-to-organ interactions. Thirdly, approaches were considered to harmonize the "triage-methods" used on an international level using the "Response Category" approach as developed for the European Communities. These discussions lead to the conclusion that there is a strong need for continuing education of physicians, nurses, and support personnel to address the issues posed by the management of patients suffering from radiation syndromes. Finally, the discussions expressed the need for more international cooperation in research and development of more refined methods to treat patients with any type of radiation syndromes.

Radiologic and nuclear events: contingency planning for hematologists/oncologists.

Untoward events involving radioactive material, either accidental or intentional, are potentially devastating. Hematologists and oncologists are uniquely suited to help manage radiation victims, as myelosuppression is a frequent complication of radiation exposure. In the aftermath of a large event, such as a nuclear detonation, there may be a national call for surge capacity that involves hematologists/oncologists across the country in the disaster response. In preparation, the National Marrow Donor Program and American Society for Blood and Marrow Transplantation have established the Radiation Injury Treatment Network (RITN), a voluntary consortium of transplant centers, donor centers, and umbilical cord blood banks. RITN is partnered with the Office of the Assistant Secretary for Preparedness and Response in the United States Department of Health and Human Services to develop treatment guidelines, educate healthcare professionals, coordinate situation response, and provide comprehensive evaluation and care for radiation injury victims. We outline the current plans for event response and describe scenarios, including catastrophic events that would require extensive support from hematologists/oncologists across the country. In addition, we highlight important reference resources and discuss current efforts to develop medical countermeasures against radiation toxicity. Practitioners and institutions across the country are encouraged to become involved and participate in the planning.