FORT LIBERTY, N.C. — Team members with the U.S. Army Medical Materiel Development Activity joined dozens of U.S. Army medics at Fort Liberty, North Carolina, to assess the progress of several traumatic brain injury detection devices as part of a Soldier touchpoint this week.

The Soldiers provided feedback on two brain trauma assessment devices currently under development at USAMMDA under the management of the Warfighter Readiness, Performance and Brain Health Project Management Office and stakeholders with the North Carolina Center for Optimizing Military Performance. The event, which included combat casualty assessment lanes inside Fort Liberty’s Iron Mike Conference Center, was designed to assess the progress of TBI Field Assessment Device program and inform future program development. Feedback from prospective end users — U.S. Army medics, medical officers, and combat troops — is a vital step in development programs, according to U.S. Army Lt. Col. Dana Bal, a product manager with WRPBH.

“These types of end-user interfaces are vital to what we do in the WRPBH PMO,” said Bal. “The information we gather — both from our own observations as advanced developers and from the critiques we get from the medics and medical officers actually using the device — is incredibly important to how we approach the development process. Our ultimate goal is to develop materiel solutions that meet the needs of the Warfighters, and we couldn’t do that without these types of opportunities.”

During the touchpoint, volunteer Soldiers from multiple units assigned to the U.S. Army’s largest base conducted TBI assessments on role player casualties to determine the effectiveness of the devices in a simulated real-world environment. The event was designed to gauge the effectiveness of the TBI assessment devices to detect possible brain trauma outside a clinical environment, like those found at U.S. Army role 1 and role 2 care facilities. The Soldiers provided feedback about the devices’ ease of use, design features and overall fitness for use in austere, remote environments.

“These development programs can last years, starting with identifying a capability gap or unmet treatment need, through design, modifications and FDA approval, and finally, fielding products to U.S. military medical providers and units, including through sustainment of these capabilities,” said Bal. “With the need for rugged, reliable, user-friendly devices to aid in assessing possible TBIs, we are focusing more and more on how to meet the current and future needs of military medical providers, and hearing feedback from subject matter experts helps refine our approach.”

Traumatic brain injuries, caused by exposure to concussive events like roadside bombs and indirect fire, are a significant threat to frontline service members. There have been more than 505,000 traumatic brain injuries reported within the Department of Defense since 2000, ranging from mild to severe. Many TBIs are not accompanied by exterior signs of injury yet can have both short and long-term health effects. In TBI cases, identifying internal injuries, like intercranial hemorrhage or other non-visible brain damage, is a vital first step to ensure injured are treated adequately across the continuum of care.

The WRPBH TBI assessment programs are designed to develop devices that are rugged, deployable, cost-effective and user-friendly in the hands of medical providers as close to the point-of-injury as possible. This allows the providers to shape treatment decisions before, during, and after medevac post-injury, according to U.S. Army Sgt. 1st Class Andrew Procter, senior enlisted advisor for USAMMDA’s Soldier Medical Devices PMO.

“TBIs can be very hard to recognize immediately after a concussive event because there usually no visible signs of injury,” said Procter, a medic with nearly 20 years of experience and multiple deployments across the globe. “Medics and first responders usually focus on outward signs of injury — bleeding, burns, airways, broken bones, things that are immediately apparent after injury — to stabilize a patient before medevac. Because determining the severity of TBIs requires specialized screenings and imaging devices, it’s tough to accurately diagnose the severity and type of brain injury in a field environment. But what we are doing now, what the WRPBH team is focusing on, will hopefully give future medics and first responders a way to recognize TBIs and assess their severity before evacuation decisions are even arranged.”

During recent conflicts in Iraq and Afghanistan, wounded service members were usually less than an hour from higher echelons of care due to the availability and proximity to the front lines of evacuation aircraft and vehicles. The “Golden Hour” roughly described the minutes immediately after a wound occurred and indicated the amount of time medical providers had to assess a casualty, stabilize them, and arrange for evacuation. But during future conflicts, with logistics and evacuation capabilities limited by distance and austerity found in regions like the Arctic and Indo-Pacific, the Golden Hour may not be a feasible amount of time to move injured and wounded to higher care facilities. To answer the TBI treatment challenges presented by possible future conflicts in remote locations, the USAMMDA team works each day to develop new capabilities and improve tested treatments to meet the needs of tomorrow’s Warfighters, said Procter.

“Our Joint Force medical providers have had a very robust logistics capability the past quarter century and our ability to save and preserve lives has been unmatched by any period in history. What we recognize, however, is that our current treatments for injuries are very much tied to our ability to move casualties rapidly from point-of-injury to more advanced facilities further from the front lines,” said Procter. “The TBI assessment programs we’re currently developing will hopefully go a long way to maximizing ground commanders’ evacuation options, limit unneeded evacuations, shorten the time from injury to the start of treatment, and help keep Warfighters in the fight.”

USAMMDA develops, delivers and fields critical drugs, vaccines, biologics, devices and medical support equipment to protect and preserve the lives of Warfighters across the globe. USAMMDA Project Managers guide the development of medical products for the U.S. Army Medical Department, other U.S. military services, the Joint Staff, the Defense Health Agency and the U.S. Special Operations community.

The process takes promising technology from the Department of Defense, industry, and academia to U.S. Forces, from the testing required for U.S. Food and Drug Administration approval or licensing to fielding and sustainment of the finished product. USAMMDA Project Management Offices will transition to a Program Executive Office under the Defense Health Agency, Deputy Assistant Director for Acquisition and Sustainment.

By T. T. Parish

Altitude sickness emerged as a human concern thousands of years ago, and not just out of thin air. Even with years of studying the symptoms and impact on the body, it still affects many people who ascend to altitudes above 8,000 feet.

The U.S. Army Research Institute of Environmental Medicine and the University of New Mexico are creating a predictive tool to transform the way altitude-related health illnesses are managed and prevented during military operational exercises.

“Altitude can really knock a person off their feet,” says Beth Beidleman, Sc.D., the study’s Principal Investigator and Research Physiologist in the Military Performance Division at USARIEM.

Acute mountain sickness may cause an individual to have headaches, nausea, vomiting, dizziness and severe fatigue due to the lower air pressure and decreased availability of oxygen in the environment at higher altitudes. Generally, the higher in altitude you go; the sicker you get, but the sickness is highly individualized. Some may get sick while others will be just fine. Typically, the sickness peaks between 18 to 24 hours and then resolves over the next two to three days.

“AMS affects everything a person does. You can’t run, think and even breathing is difficult. It also jeopardizes physical and mental performance,” Beidleman said. “While there are medications available to reduce symptoms, they are not always effective, and it is uncertain whether they negatively impact physical performance. We want to help our Soldiers and enable them to complete their mission, and that is what this study is about.”

The current tool is a wearable wrist monitor that tracks the amount of oxygen in the body’s bloodstream and links this health information to the patented AMS_alert algorithm, which predicts an individual’s likelihood of experiencing AMS four to eight hours before symptoms.

Over a period of six weeks at USARIEM’s High Altitude Research Laboratory in Pikes Peak, Colorado, data was collected from 32 active-duty Soldiers from Fort Riley, Kansas, and the Human Research and Development Detachment in Natick, Massachusetts, with the goal of improving the AMS_alert algorithm’s accuracy.

With this algorithm, leaders can see who may be at high risk early in the altitude exposure and possibly prevent injuries and casualties that could occur later in the exposure. This was the last iteration of the study conducted to expand the altitude range from the previous version at 12,000 feet above sea level at Taos Ski Valley, New Mexico to over 14,000 feet, so that the AMS_alert algorithm includes higher altitudes.

“Hypoxia monitoring can help detect future altitude sickness and therefore allow early intervention so that Soldiers can complete a successful mission. The goal is to have a smart phone application that houses the algorithm to provide a green, yellow and red alert to leaders and Commanders in the field on the health status of their Soldiers,” Beidleman said.

Every morning for two weeks, each cohort of Soldiers had a typical rhythm of waking up at 6:00 a.m., providing a saliva sample, a blood draw, and a urine and fecal sample, and reporting symptoms of AMS. The participants then had breakfast before they performed a breathing test, cognitive function assessment and ultrasound of their lungs and spleen. The morning ended with an all-out two-mile run and a two-to-three-mile hike. Following lunch, Soldiers participated in alpine training offered by physicians with experience in Mountain Medicine from the University of New Mexico. At the end of the day, participants completed additional AMS questionnaires.

“Everything the Soldiers did at altitude over the course of four days, from waking up in their bunks in the High Altitude Reasearch Lab to hiking in the mountains, was conducted at 13,500 to 14,300 feet,” said Beidleman.

One goal of this research is to replace the Environmental Symptoms Questionnaire with a diagnostic blood or urine test, given that Soldiers typically underreport their symptoms. To do this, Beidleman is analyzing metabolic and genomic biomarkers that have been previously shown to diagnose AMS.

Another mission in this research is to collect these biomarkers at sea level, prior to deployment, to assess whether an individual has a high likelihood of getting sick at altitude. Beidleman notes that genomics play a role in every other sickness, including cancer and Alzheimers, and likely plays a role in altitude illnesses as well.

In addition to using this tool to predict AMS, it could potentially be used to mitigate life-threatening events such as high-altitude pulmonary edema — fluid in lungs — and cerebral edema — fluid in brain — that can develop at high altitude by providing alerts prior to such events from occurring. Although these illnesses are relatively rare, these events require immediate evacuation.

“One thing about the wearables is that they monitor various physiologic metrics like heart rate and sleep activity, but we also want to compare current FDA-approved technology to validate our proprietary devices that will house the AMS_alert algorithm,” said Melissa Mcinnis, Oak Ridge Institute for Science and Education fellow at USARIEM.

This research has become one of USARIEM’s biggest multi-divisional and collaborative studies. While collaborating with experts at the University of New Mexico, USARIEM is also working with the Walter Reed Army Institute of Research, Air Force Research Laboratory.

“Acute mountain sickness can be a debilitating condition. With this tool, Warfighters will be able to make better informed decisions before the onset of more severe symptoms,” said Steven Landspurg, ORISE fellow at USARIEM.

The research team aims transition to the U.S. Army Medical Materiel Development Activity for launch of the app by early fall of 2025. Beidleman says that this tool can go beyond military purposes and expand to civilian use.

USARIEM is a subordinate command of the U.S. Army Medical Research and Development Command under the Army Futures Command. USARIEM is internationally recognized as the DOD’s premier laboratory for Warfighter health and performance research and focuses on environmental medicine, physiology, physical and cognitive performance, and nutrition research. Located at the Natick Soldier Systems Center in Natick, Massachusetts, USARIEM’s mission is to research and deliver solutions to enhance Warfighter health, performance and lethality in all environments.

Story by Maddi Langweil 

Medical Research and Development Command

FORT DETRICK, Md. – A new invention developed at the U.S. Army Medical Research and Development Command uses an artificial intelligence machine learning algorithm to identify whether burn patients are at risk of experiencing life-threatening complications from sepsis. The invention has been submitted to the U.S. Food and Drug Administration for an initial guidance review, a crucial step on the path to readying the device for commercial licensing.

SeptiBurnAlert, invented by Dr. Rasha Hammamieh and Nabarun Chakraborty of the Medical Readiness Systems Biology branch of the Center for Military Psychiatry and Neuroscience at MRDC’s Walter Reed Army Institute of Research, analyzes blood samples taken from a burn victim to identify the presence of specific biomolecular changes, called biomarkers, that are associated with an elevated risk of dangerous inflammation triggered by the body’s attempts to fight infection. By using a combination of rapid biomolecular assay and a specially trained algorithm, the device promises to allow intensive care teams to predict the risk of sepsis onset within the first 24 hours of a patient’s admission to the intensive care unit, greatly improving the patient’s odds of survival.

Although improvements in combat casualty care have made it possible for 95% of burn patients to survive their injuries, over 30% experience sepsis, the leading cause of death among patients with acute burn injuries. That’s because burn patients lose their first and most effective barrier to infection: their skin. As long as the wound remains open, patients are exposed to a wide range of harmful agents that can challenge the body’s immune system and trigger an inflammation response, which in turn increases the risk of sepsis. But diagnosing sepsis in burn patients is difficult and time-consuming.

“Many of the standard indicators that clinicians use to identify sepsis are already present in burn patients,” explains Chakraborty. “High temperature, shortness of breath, low blood pressure and delirium are common to both, which often impedes clinicians’ ability to identify sepsis in burn patients. For burn patients who are at risk of developing sepsis, it may remain undetected for a long time, increasing their risk of mortality. Likewise, for burn patients who are not at risk of developing sepsis, they may be given antibiotics that they don’t need. That is the challenge we are trying to solve.”

SeptiBurnAlert uses a process called polymerase chain reaction to analyze blood samples taken from a burn patient to detect the presence of six genes that are associated with the onset of sepsis. The amounts of those genes in the blood samples are then analyzed by a proprietary machine learning algorithm, developed by Chakraborty and several colleagues, that has been trained on blood samples obtained from a study conducted by Dr. Jeffrey Shupp at MedStar Washington Hospital Center in Washington, DC, one of the country’s leading burn treatment centers. This allows the algorithm to predict the risk of sepsis onset in the patient much more quickly than existing methods, which can require around 100 hours after ICU admission to provide results.

During initial tests, which Hammamieh and Chakraborty conducted with their colleagues Dr. Aarti Gautam and Alexander Lawrence, SeptiBurnAlert accurately assessed sepsis risk in blood samples to a high degree of accuracy. MRDC’s Combat Casualty Care Research Program is currently testing the biomarkers in two ongoing studies to further validate their efficacy. Before SeptiBurnAlert can be used in hospitals, however, it must first meet safety and efficacy criteria developed by the FDA, which regulates all medical devices sold in the U.S.

To ensure that it does, MRDC’s Office of Regulated Activities recently submitted a request to the FDA to review the device and provide feedback on whether additional validation studies are needed, if there are any privacy and security concerns that need to be addressed and whether the device meets all applicable regulatory standards. ORA’s regulatory affairs, compliance and clinical support professionals act as liaisons between MRDC inventors and the FDA to guide them through the review process, helping to mitigate risks and accelerate the delivery of regulated medical devices to market.

Chakraborty says that one advantage of SeptiBurnAlert is that it uses existing off-the-shelf technology and methodologies to analyze the set of six genes, which is called an assay.

“Every lab and clinical facility has PCR devices,” says Chakraborty. “They just need our assay. That will help clinicians gain confidence in the assay. Then, maybe in three or four years, we’ll launch a fully automated version that could be carried to far-forward locations to deliver results before the patient’s ICU admission. This would be an effective step toward achieving customized disease management.”

Hammamieh, Chakraborty and their team have applied for a worldwide patent for the biomarker assay used in the device. They have been working with MRDC’s Small Business Innovation Research and Small Business Technology Transfer Programs, as well as with the MRDC Office of Medical Technology Transfer, on the second-generation model of SeptiBurnAlert, which will be able to analyze a larger assay. SBIR/STTR is currently researching potential sources of developmental funding.

“SeptiBurnAlert has great potential to save the lives of Warfighters and civilians all over the world,” says Dr. Edward Diehl, a commercialization officer with MTT. “We are actively pursuing a license agreement with commercial partners to allow further development of this technology.”

As well as being a potential game-changer in its own right, SeptiBurnAlert is a good example of how MRDC’s multidisciplinary approach drives innovation. The idea for SeptiBurnAlert occurred to Hammamieh and Chakraborty when they were conducting an unrelated study, seeking to identify biomarkers associated with impaired blood coagulation in burn patients.

“As part of this study, we collected blood samples from burn patients shortly after they arrived in the intensive care unit, a number of whom developed sepsis three or four days later,” recalls Hammamieh. “We wondered, ‘Could some of the biomarkers we’re collecting help us predict who will develop sepsis?’ When we completed the coagulopathy study, then it was just a matter of reanalyzing the data we collected for it to look for particular genes, proteins and metabolites that differed between the people who developed sepsis and those who did not.”

ORA submitted the request for a guidance review, called a Q-Submission, to the FDA in late August. Once the FDA reviewers have examined the SeptiBurnAlert device and its supporting data, the ORA team and the inventors will then meet with them to discuss the regulatory pathway forward and any future studies that might be needed to address any unresolved issues.

“We’re looking forward to working with the FDA to ensure that SeptiBurnAlert is safe for use and effective at predicting the risk of sepsis in burn patients,” says Hammamieh. “We are only at the beginning of the review process, but we are excited and hopeful that the device will soon be in use in intensive care units across the U.S., helping to save lives.”

By Paul Lagasse, USAMRDC Public Affairs Office