MAX Magazine - Spring 2025

FROM THE DESK OF DR. WARD The Collaborative Advantage of Team Science Years ago, Harvard Business School Professor Rosabeth Moss Kanter argued that “companies’ individual success relies intimately on their ability to maintain collaborative relationships with other organizations.” The key features of successful collaborations between individual companies, she pointed out, were that they opened doors to unforeseen opportunities, created new value rather than simply being a zero-sum exchange, and were not controlled by a single entity but flourished from equal contributions from all stakeholders.

She dubbed this the “collaborative advantage.” 1 We at the Weil Institute strongly believe in and embrace the collaborative advantage and its potential for impact. The complexity and challenges of critical care and its toll on health and the economy demand it! While it’s easy to talk the talk about this, it is quite a different matter to practice it every day.

Regarded as a founder and father of critical care medicine, Dr. Max Harry Weil conceived of putting critically ill patients together in a single area where they could be cared for by an interdisciplinary team of doctors, nurses, and other health professionals. His work would establish a new field of medicine, save countless lives, and forever change how care is delivered. This included the development of unconventional but integrated research teams that included engineers and basic scientists. Today, the Weil Institute’s mission is in lockstep with Dr. Weil’s vision: transform critical care. It’s a simple word (transform), but, like the field itself, the singular goal behind that word is incredibly complex and, like Dr. Weil, we know transformation takes a team.

1. https://hbr.org/1994/07/collaborative-advantage-the-art-of-alliances

The Weil Institute is distinctive in that we are strategically integrated throughout the University of Michigan to connect all types of critical care clinical providers with basic scientists, engineers of many types, computer and data scientists, and many other departments, schools, colleges, and units across the university, to transform care from every angle. We provide these teams with unique essential support services that lower the energy barrier to form the collaborative advantage of team science and enable them to quickly and effectively take their ideas from concept to reality.

It is my sincere pleasure to provide you with the second edition of MAX Magazine. In these pages, you will see example after example of exciting research, technologies, and therapies that took team science to a new level—utilizing their “collaborative advantage” to redefine what we know as critical care. I invite you to explore our stories and see how the Weil Institution is empowering the collaborative advantage to transform critical care through innovation, integration, and entrepreneurship.

Kevin Ward, MD Executive Director, Max Harry Weil Institute

Editor

Contributing Writers & Featured Perspectives

Megan VanStratt

Florian Schmitzberger, MD Kevin Ward, MD Robert Dickson, MD Kathleen Stringer, PharmD

Design Kate Murphy

Meagan Ramsey, PhD Jenna Wiens, PhD Kayte Spector-Bagdady, JD, MBE Bhramar Mukherjee, PhD

Sardar Ansari, PhD Brittany Baur, PhD Karandeep Singh, MD, MMSc Andrew Admon, MD, MPH, MS

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ISSUE FOCUS: INTERDISCIPLINARY COLLABORATIONS IN CRITICAL CARE

WEIL MEMBER PERSPECTIVES

4 We Asked a Weil Member

Featuring Kathleen Stringer, PharmD

8 The AerosolVE BioHelmet: Protection for Patients, Confidence for Caregivers 14 Linking Sepsis & Cholesterol

28 Harnessing the Power of Military-Academic Partnerships to Improve Battlefield Medical Outcomes

18 COVER STORY: Answering the Call - Team Science in Action at the Weil Institute

30 Toward Realizing the Promise of AI in Precision Health Across the Spectrum of Care

24 A Data Science Solution for a Critical Supply Crisis

32 How Weil Grants Benefit Patients

26 Weil Team’s Culture-Free Tool Expedites Diagnosis of Bloodstream Infections

37 Challenges in Post-market Monitoring of Clinical Prediction Models

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MORE STORIES FROM THE WEIL INSTITUTE 6 Featured Weil Member Research

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RESOURCES FROM WEIL PARTNERS 42 Great Lakes I-CORPS

• Development of an Ultrasound-based Flow-pressure Index for the Assessment of Cerebral Autoregulation

43 AI & Digital Health

• How Metabolism Affects Blood Biomarkers in Sepsis and ARDS

47 Innovation Partnerships

• The Role of Cholesterol in Immune Response to Sepsis

Innovation (FFMI)

Innovation (AI&DHI)

47 Fast Forward Medical

• Wearable Sensor Detects Impending Cardiac Events

12 A Meeting for the Minds: The NeuroEM K12 Program 17 Catching Up With: The Great Lakes Clinical Center of the APS Phenotyping Consortium 38 Catching Up With: The Acute and Critical Care Engineering Training Program

Published by the Max Harry Weil Institute for Critical Care Research and Innovation 2800 Plymouth Road North Campus Research Complex Building 10, Room A-106 Ann Arbor, MI 48109

weilinstitute.org

Weil-Institute

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WE ASKED A WEIL INSTITUTE MEMBER What does the history of innovation in critical care medicine tell us about the discipline’s future?

It tells us that the discipline’s future will continue to be shaped by technological advancement, interdisciplinary collaborations, and precision pharmacotherapy strategies.

K.S.

An essential feature is interdisciplinary collaborations. This is because technological evolution drives paradigm shifts which requires expertise from several different disciplines. From the advent of mechanical ventilation and hemodialysis to ECMO and continuous vital sign monitoring, each major technological leap has redefined what is possible in the ICU. Future innovations—like closed-loop systems, AI-driven decision support, and wearable biosensors—are likely to similarly revolutionize care delivery and monitoring.

Achievement of precision pharmacotherapy will also require the minds of many with different expertise. The growing understanding of mechanisms that contribute to the heterogeneity of sepsis and ARDS will lead to biomarkers that differentiate phenotypes.

Collectively, this work will identify drug target opportunities and associated biomarkers that can be used to identify patients that are most likely to respond to a specific treatment.

In addition, future targeted pharmacotherapies will be identified based on genomics, metabolomics, and microbiome profiles.

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What is on your critical care innovation wish list?

Biomarker directed pharmacotherapy that evolves from understanding the mechanisms that drives the heterogeneity of critical illnesses.

K.S.

What words of advice do you have for future researchers and clinicians in critical care?

Be persistent. Never give up and most importantly, work with fully committed, like-minded collaborators with a broad range of skills that complement and synergize with yours.

K.S.

FEATURING

Kathleen Stringer, PharmD Deputy Director, Weil Institute; Albert B. Prescott Collegiate Professor, Clinical and Translational Pharmacy Dr. Stringer is a clinical pharmacist by training but has spent most of her career as a translational researcher in critical care.

Her long-term goal is to bring targeted, biomarker informed pharmacotherapies to patients with sepsis. This is an enormous undertaking that requires the minds and skills of a highly committed team of collaborators who share this vision.

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FEATURED WEIL INSTITUTE MEMBER PROJECTS

NEW DEVICE & METHODOLOGY

RESEARCH STUDY

Development of an Ultrasoundbased Flow-pressure Index for the Assessment of Cerebral Autoregulation

How Metabolism Affects Blood Biomarkers in Sepsis and ARDS

Following a traumatic brain injury (TBI), the blood vessels can lose their ability to autoregulate blood flow to the brain. This loss of cerebral autoregulation (CA) has a major impact on outcomes after TBI, yet the gold-standard method for measuring CA is difficult as it requires continuous monitoring of mean arterial pressure (MAP) and intracranial pressure (ICP) through the placement of a highly invasive monitor.

Led by Dr. J. Brian Fowlkes, Professor of Radiology and Biomedical Engineering, and Dr. Hakam Tiba, Research Associate Professor of Emergency Medicine, researchers are developing an alternative, non-invasive system for measuring CA. Using an ultrasound technology developed at U-M, the team is analyzing internal carotid artery flow (ICA) and middle cerebral artery flow (MCA) as potential replacements for ICP. The team will combine these measures with MAP to build indices which, through the support of a renewed Massey grant, they are now in the process of validating in a preclinical model.

Weil Institute Support Provided

Proposal Development

Developing targeted treatments for sepsis and acute respiratory distress syndrome (ARDS) is challenging due to the conditions’ heterogeneity—the variability in their clinical and biological features.

Led by Dr. Kathleen Stringer, a Deputy Director of the Weil Institute and Albert B. Prescott Collegiate Professor of Clinical and Translational Pharmacy, the research program “Translational Metabolomics in Critical Care” aims to solve this problem by studying how metabolism provides information about health, illness, and drug response in sepsis and ARDS. The information Dr. Stringer and her team acquire from this work could help determine what signals in the blood could be used to develop new therapies for these critical illnesses.

Weil Institute Support Provided

Funding Mechanisms Engaged National Institute of General Medical Sciences Maximizing Investigators’ Research Award

Data Science Services

Preclinical Laboratory

RESEARCH STUDY

DEVICE DEVELOPMENT

The Role of Cholesterol in the Immune Response to Sepsis

Wearable Sensor Detects Impending Cardiac Events

Increasing usage of antibiotics in the treatment of sepsis and other bacterial conditions has led to growing concerns over the development of medication-resistant superbugs.

Supported by a $1 million grant from the American Heart Association, investigators led by Dr. Kenn Oldham, Associate Director of the Weil Institute and Professor of Mechanical Engineering, are studying the use of a Weil Institute-developed wearable sensor called the “Vascular Tone Monitoring System” (VATMOS) to non-invasively track changes in vascular resistance. This measure is a key component in blood pressure regulation and provides a clinically-relevant source of valuable insight into the cardiovascular system’s response to disease and injury.

In a previous study conducted using a zebrafish model of inflammation, Weil Institute K12 scholar Dr. Vinitha Jacob, Assistant Professor of Emergency Medicine, found that by inhibiting a

specific gene vital to cholesterol production, she was able to completely rescue the fish from endotoxemic death.

Now, Dr. Jacob aims to determine the mechanisms behind this and to understand whether these effects can be reproduced in mammals. She also seeks to identify clinically available gene inhibitors that could be potentially repurposed for use in humans.

Weil Institute Support Provided

The grant is being conducted in collaboration with the University of North Texas Health Science Center. Initial testing of VATMOS was performed in the Weil Institute Preclinical Critical Care Laboratory through several previous Massey TBI Grand Challenge awards. The published data from these experiments was used to obtain the American Heart Association award.

Weil Institute Support Provided

Funding Mechanisms Engaged National Institute of General Medical Sciences K08 Grant

Funding Mechanisms Engaged American Heart Association

Clinical Research Team

Product Commercialization

Grand Challenge Events

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PROTECTED AT 41,000+ FEET The AerosolVE BioHelmet was engineered to isolate the wearer in plain sight while keeping those around them safe from viral spread.

The goal was for the helmet to be completely effective even in small, crowded spaces—such as the cabin of a U-M Survival Flight Lear Jet! Photo courtesy of the AerosolVE team

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PROTECTION FOR PATIENTS, CONFIDENCE FOR CAREGIVERS What began as a conversation between a father and daughter would become a life-saving example of clinical and engineering collaboration.

that could be deployed to protect patients and those around them no matter where they may be while still enabling care providers to carry out the various procedures needed to restore the patient’s health.

The result was the AerosolVE BioHelmet.

AerosolVE: Personal Protective Equipment for the Patient

The COVID-19 pandemic underscored an urgent need for solutions capable of curbing the spread of highly transmissible respiratory diseases while enabling the safe transport and treatment of patients with these conditions.

One current strategy is to place patients with highly transmissible conditions into negative pressure rooms—specially equipped spaces that allow fresh air to flow in while preventing contaminated air from flowing out. However, these systems are costly, fixed, inflexible spaces and are virtually nonexistent in less-resourced health

systems. Moreover, while negative pressure rooms effectively prevent viral particles from escaping into the environment outside of them, they are not designed to protect the patients and healthcare teams who are inside of them.

In 2020, a team of engineers and clinicians led by Dr. Sridhar Kota, CEO of InspireRx, Herrick Emeritus Professor of Engineering and a member of the Weil Institute, sought to address the emerging needs resulting from the pandemic by taking the concept of a negative pressure room and turning it into a personal, more portable form

The AerosolVE BioHelmet instantly isolates patients with any highly transmissible respiratory infectious disease wherever they are—whether in an ambulance, waiting room, intensive care unit, or even a hallway. Worn around the patient’s head, the device pulls ambient air into the helmet and subsequently directs this air with the patient’s exhaled breath through an attached HEPA filter to remove pathogens. The rate of flow produced is adjustable, and it provides up to 800 air exchanges per hour—70 times more than a traditional negative pressure room at a fraction of the cost. The helmet is also designed to accommodate non-invasive oxygen treatments such as high-flow nasal cannula, aerosol masks and continuous positive airway pressure (CPAP) devices, helping to spare the need for

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BRINGING THE HELMET INTO THE HOSPITAL

Dr. Ben Bassin (right), tests a prototype of the AerosolVE Helmet in 2020.

A key consideration at this stage was ensuring that the helmet’s air flow prevented infectious aerosols from escaping while also enabling care teams to perform life-saving procedures that are known to generate these aerosols.

Photo courtesy of the AerosolVE team

mechanical ventilation. Even when these therapies are used, there will be no need for a negative pressure room.

“It started as a simple and straightforward idea conceived while brainstorming with my daughter, Shalini Kota,” said Dr. Kota. “What followed was a quick prototype to meet an urgent need, which would go on to save lives within a few weeks thanks to Drs. Ben Bassin, Nathan Haas and Kevin Ward.

That, to me, was the most gratifying outcome of all.”

“It was almost as if we were putting personal protective equipment (PPE) on the wrong people,” said Shalini Kota, MS, who is a Clinical Research Coordinator at the Weil Institute. “I thought, what if, in addition to putting PPE on healthcare workers, we tried to go a little bit upstream and mitigate virus spread at the patient?”

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The Future of the BioHelmet

The BioHelmet led to another complimentary technology of the AerosolVE team’s personal negative pressure systems—the AerosolVE tent, which would go on to receive Emergency Use Authorization from the U.S. Food and Drug Administration (FDA) in 2021.

In 2024, the company would then receive over $2 million in Small Business Innovation Research (SBIR) grants from the National Institutes of Health (NIH) and the Centers for Disease Control and Prevention (CDC) to support further development of the BioHelmet.

AerosolVE is now focusing on refining the design of the BioHelmet for better comfort and ease of manufacturing and to reduce weight and cost. Once the prototype helmets have been manufactured, the team will measure key aspects

like particulate filtration, electrical safety and environmental stability.

They will gather feedback from clinicians, hospital administrators, and other stakeholders to ensure the BioHelmet meets practical and operational needs. They will also perform comprehensive evaluations on patient comfort and device usability in both ground and air ambulances and perform various performance and safety tests following FDA guidelines.

“The BioHelmet both creates and maintains a personal negative pressure environment around the wearer during ambulance and hospital transport, radiographic imaging testing, and treatment, and its compact design even allows the patient to walk around while wearing it,” said Dr. Ben Bassin, a Co-Investigator on the NIH grant and a member of the Weil Institute.

TIMELINE OF INNOVATION

AEROSOLVE 2020

The COVID-19 pandemic sparks a conversation about negative pressure rooms between Sridhar and Shalini Kota. The image of an astronaut helmet on a greeting card inspires Shalini to propose the idea of putting a negative pressure “helmet” on patients, mitigating viral spread at the source.

Dr. Kota presents the idea to Dr. Kevin Ward at the Weil Institute the next day. Two days later, a prototype is built and is later authorized to be used at U-M Health under an emergency protocol.

The success of the prototype helmet spurs the initial development of a complimentary technology: a portable, negative pressure procedural tent that effectively turns any bed into an ICU bed.

2021 InspireRX LLC. is formed to further develop and commercialize the tent and helmet devices, with Dr. Kota as CEO and Dr. Ben Bassin as CMO. The AerosolVE Tent receives Emergency Use Authorization from the FDA. The tent enables UM physicians to perform surgical procedures, such as tracheostomy and bronchoscopy, that they would otherwise not risk on Covid-19 patients. Countless inquiries expressing interest in the BioHelmet pour in from hospitals across the country, including the US Department of Health and Human Services.

In 2021, the Toledo Blade interviewed Shalini Kota about the AerosolVE BioHelmet.

Check it out here!

2024 Working with Meagan Ramsey, PhD, the Director of the Weil Institute’s Proposal Development Unit, the AerosolVE team secures a $1,828,885 grant from the National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health (NIH) and $295,924 grant from the Centers for Disease Control and Prevention (CDC) to propel development of the AerosolVE BioHelmet.

The team is now refining the design of the BioHelmet, gathering feedback from key stakeholders, performing comprehensive evaluations on patient comfort and device usability in both ground and air ambulances, working with a Michigan-based medical device company for scale-up production and preparing FDA pre-market authorization application.

As Medical Director for the Michigan Medicine Emergency Critical Care Center (EC3)—the nation’s first intensive care unit housed within an emergency department—as well as Associate Medical Director for Survival Flight, Dr. Bassin feels that the BioHelmet is a complete gamechanger.

“This provides negative pressure across almost any environment, whether it’s in a hospital room, a waiting room, a helicopter or a cruise ship,” said Bassin. “It keeps the patient, the healthcare providers and the families safe wherever that might be and allows for optimization and flexibility of resource allocation.”

Weil Institute Support

On both the NIH and CDC grants, Weil’s Proposal Development Team provided significant support, including assessing the initial funding opportunities, providing strategic consultation, meeting with program officers, advising the team on agency requirements and documents, and providing proposal file checklists to help the grant teams plan and manage the writing process. The Proposal Development Team also assisted with writing and editing the grant applications.

“I cannot thank the Weil team enough for all of their support,” said Dr. Kota. “I have written countless proposals during my 34year tenure at the College of Engineering, but I never had any sort of help close to what the Weil Institute offered. They do the heavy lifting so that the PIs can focus on what they are good at.

Other entities at U-M should follow Weil’s lead on this important and often ignored aspect.”

With the support of these grants, the final iterations of the BioHelmet can now move closer to clinical use, significantly enhancing the preparedness and response capabilities of healthcare teams and systems worldwide.

“We know there will be new epidemics and pandemics in the future,” said Dr Bassin. “The BioHelmet will help ensure we are better prepared and will provide enormous flexibility in how and where we manage large numbers of ill patients in a very safe manner.”

WEIL MEMBERS FEATURED IN THIS STORY

Sridhar Kota, PhD

Herrick Professor Emeritus of Engineering; Professor Emeritus of Mechanical Engineering, Founder and CEO of Inspire Rx, LLC and FlexSys, Inc.

Shalini Kota, MS Clinical Research Coordinator, Weil Institute

Ben Bassin, MD Associate Medical Director, Survival Flight; Medical Director, Emergency Critical Care Center (EC3); Director, Technology and IP Development; Clinical Associate Professor, Emergency Medicine

Nathan Haas, MD Clinical Assistant Professor, Emergency Medicine

Kevin Ward, MD Executive Director, Weil Institute; Professor, Emergency Medicine; Professor, Biomedical Engineering

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AT THE INAUGURAL RETREAT Neuro-EM Scholars Retreat attendees meet at the Graduate Hotel for the inaugural annual retreat. In front: Keynote speaker Dr. Walter Koroshetz (center) with members of the Neuro-EM Scholars leadership team and National Advisory Committee. In back: The eight K12 scholar applicants and fifteen Pipeline Program participants.

A MEETING FOR THE MINDS New K12 program at the Weil Institute trains early-career Emergency Medicine physicians to perform research in neurological disorders that are often treated in pre-hospital and emergency department settings.

The inaugural Neuro-EM Scholars Program, a new national K12 program housed at the University of Michigan Max Harry Weil Institute for Critical Care Research and Innovation, has funded four scholars in 2025.

These scholars successfully competed for funding by submitting a K12 grant proposal, then interviewing with NeuroEM program leaders during the inaugural Neuro-EM Retreat in December 2024. The scholars will receive up to three years of K12 funding to support their research 12

and career development, with 75% of their effort dedicated to research and research training.

The Neuro-EM Retreat was planned and managed by the Weil Institute Events and Proposal Development teams. The event, which took place in Ann Arbor, MI, hosted 49 attendees representing 28 universities and research institutions across the United States.

Attendees included the Neuro-EM Co-Directors and National Advisory Committee, comprising 19 senior leaders in emergency medicine and other neuro specialties.

The retreat also hosted 22 early career emergency medicine residents, fellows and first- and second-year faculty, including 7 K12 scholar applicants and 15 participants in the Neuro-EM Pipeline Program. Additional attendees included representatives from the National Institutes of Health (NIH) and invited speakers.

The keynote address was provided by Dr. Walter Koroshetz, Director of the National Institute of Neurological Disorders and Stroke (NINDS), who spoke on the past and present state of research on

The Weil teams did amazing work to make the inaugural Neuro-EM retreat a resounding success.

The feedback was uniformly glowing!

- Robert Neumar, MD, PhD Co-Director, Neuro-EM Scholars Program; Professor, Emergency Medicine Member, Weil Institute

neurologic emergencies. Throughout the four-day event, 17 other presentations and panels covered a range of topics related to emergency medicine research, grant writing and career development. Several of the sessions were recorded and will be posted to the Neuro-EM Program website later this year.

“The Weil teams did amazing work to make the inaugural NeuroEM Scholars retreat a resounding success,” shared Dr. Robert Neumar, Co-Director of the Neuro-EM Scholars Program, Professor of Emergency Medicine and a member of the Weil Institute. “The feedback from attendees was uniformly glowing.”

The overall Neuro-EM K12 Program and three of the scholars are funded by NINDS, while one scholar in this first cohort is funded by the National Institute on Aging

(NIA). Future Neuro-EM scholars may also be funded by the National Institute on Drug Abuse (NIDA).

The Neuro-EM Pipeline Program is supported by the National Foundation of Emergency Medicine.

Neuro-EM research and career development webinars began in the spring and are open to anyone. Those interested can sign up to receive program updates on the Neuro-EM Scholars website (neuroemscholars.org). The website also provides eligibility information and application details for the K12 and Pipeline programs.

Early career emergency medicine physicians (senior residents, fellows, or first- or second-year faculty members) interested in performing research focused on neurological disorders commonly treated in the pre-hospital and emergency department settings may

be eligible for the either the NeuroEM Pipeline Program or the K12 Scholar Program.

Those interested in becoming a K12 Scholar must submit an LOI

by September 3, followed by the official application due October 1. Nominations for the Pipeline Program will be due September 15.

The next Neuro-EM Retreat will take place December 2-5, 2025.

More Information

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LINKING

Multi-institute, cross-discipline mentorships empowered a Weil Institute K12 scholar’s study on the role of cholesterol levels in sepsis outcomes.

Sepsis is a life-threatening medical emergency that occurs when the body’s dysregulated response to an infection causes uncontrolled inflammation and widespread organ damage.

Currently, there is no cure for sepsis. The only way to treat it is to administer antibiotics that target the bacteria behind the initial infection; however, increased usage of antibiotics has led to growing concerns over the development of medication-resistant superbugs.

Additionally, nothing specific is currently available to regulate the body’s uncontrolled response to infection.

As a result of these factors, there is a critical need for new therapeutics that can alleviate sepsis toxicity while also supporting the body’s natural recovery processes.

The clinical problem of sepsis had long been an area of interest for Dr. Vinitha Jacob, Clinical Assistant Professor of Emergency Medicine at the University of Michigan. Her path to finding a potential cure eventually led her to the University of Michigan and to the Weil Institute’s Emergency Medicine Career Development Training Program.

Building upon her previous work with collaborators from the University of Florida and the University of California Los Angeles, Dr. Jacob examined a zebrafish model of uncontrolled inflammation, which recapitulated features of sepsis, alongside data from human sepsis patients.

The team found that in both the fish and human data, cholesterol metabolism genes were highly upregulated. Specifically, a gene called DHCR7, which catalyzes the last step of cholesterol production, was shown to be significantly upregulated in both human sepsis patients and in the zebrafish model of uncontrolled inflammation.

“It has been consistently shown that there is a significant association with cholesterol levels and sepsis outcomes in humans,” said Dr. Jacob.

“We don’t know these mechanisms yet, but in our zebrafish models those pathways were among the top most upregulated pathways and were on par with the inflammation-related genes that we would normally expect. That was really fascinating to us.”

Intrigued by this finding, Dr. Jacob applied a DHCR7-specific gene inhibitor to her zebrafish model and discovered that it completely rescued the fish from endotoxemic death. Now, through the support of an NIH K08 grant and the connections she made through Weil’s K12 program, Dr. Jacob aims to determine the mechanisms behind this protection and to understand whether these effects can be reproduced in mammals. She also seeks to identify clinically available DHCR7 inhibitors that could be potentially repurposed for use in humans.

While the new study is only just beginning, the knowledge that Dr. Jacob and her team gain could have significant impact on the management of sepsis and other inflammatory disorders.

“Currently, we treat sepsis supportively with broad-spectrum antibiotics, but we don’t really do anything for the dysregulated immune response,” said Dr. Jacob. “If all of this pans out, we envision giving this gene inhibitor to humans, which could enable the host to respond to infection in a more controlled fashion.”

A Career Development Capstone Operating from 2016 to 2021 through a grant from the NIH, and administered through the Weil Institute, the K12 program matched participants with mentorship teams comprised of senior clinician-scientists from fields such as emergency medicine, pulmonary and critical care, engineering, and biostatistics. The mentors helped the scholars

design personal development plans that included academic courses as well as training in clinical trial design, leadership, grant writing and data management. The goal of Weil Institute K12 training was for participants to obtain individual K or R01 funding by the end of their third year, marking their transition into productive emergency medicine research careers.

Dr. Jacob’s mentors and advisors included Dr. Jordan Shavit, Dr. Robert Dickson, Dr. Anna Schwendeman and Dr. Kathleen Stringer from the University of Michigan; Dr. Faheem Guirgis from the University of Florida; and Dr. Srinivasa Reddy from the University of California Los Angeles.

“Team science is clearly the only way to conquer diseases such as sepsis that pose tremendous challenge to human health and lives,” said Dr. Reddy. “I strongly believe that Dr. Jacob’s work in the coming years will make significant contributions to the discovery of novel therapeutic agents for treating sepsis.”

“Dr. Jacob’s zebrafish model was a very exciting way to test and validate the findings we were seeing in humans in a mechanistic model with the potential for high throughput drug screening,” said Dr. Guirgis. “This advancement for our collective work studying cholesterol and lipid metabolism in sepsis was a huge step forward, and we are excited to work with Dr. Jacob and her lab and team to advance our understanding of cholesterol metabolism in sepsis and new potential therapies.”

Connected in Search of a Cure - Dr. Vinitha Jacob & Her Multidisciplinary Mentors From left: Jordan Shavit, MD, PhD (Pediatric Hematology/Oncology, Pediatrics, Human Genetics); Robert Dickson, MD (Pulmonary and Critical Care Medicine); Anna Schwendeman, PhD (Pharmaceutical Sciences); Vinitha Jacob, MD, PhD (Emergency Medicine); Kathleen Stringer, PharmD (Clinical and Translational Pharmacy, Internal Medicine); Faheem Guirgis, MD, FACEP (Emergency Medicine); Srinivasa Reddy, PhD, MSc (Hons) (Medicine, Molecular and Medical Pharmacology) 15

Team science is clearly the only way to conquer diseases such as sepsis that pose tremendous challenge to human health and lives. I strongly believe that Dr. Jacob’s work in the coming years will make significant contributions to the discovery of novel therapeutic agents for treating sepsis.

- Srinivasa Reddy, PhD, MSc (Hon) Professor-in-Residence, Medicine, Molecular and Medical Pharmacology, University of California Los Angeles

Dr. Dickson and Dr. Stringer, who both serve as deputy directors of the Weil Institute, also shared their thoughts on the value and potential impact of Dr. Jacob’s research.

“By developing and leveraging this exciting zebrafish model, Dr. Jacob has provided the field with a way to identify critical, evolutionarily conserved pathways that contribute to sepsis, and test hundreds or thousands of potential treatments,” said Dr. Dickson. “This is precisely the kind of innovation that the field of critical care research needs, and we are lucky to have her taking full advantage of the resources of UM and the Weil Institute.”

“An added value of this model is that it can be ‘scaled up’ for testing in our swine model of sepsis. This is very exciting, as it will make her findings highly translatable and will create new opportunities for her and Weil Institute collaborators,” said Dr. Stringer.

“I felt like this was my opportunity to get things off the ground,” said Dr. Jacob. “Even though Michigan was far away from where I was originally, I took the leap and came here because of all the support I was offered through this program. Having all of these people reading my grant application and being generous with their time and resources really helped me to get to this point.”

WEIL MEMBERS FEATURED IN THIS STORY Vinitha Jacob, MD, PhD

Associate Professor of Emergency Medicine

Robert Dickson, MD

Galen B Toews MD Legacy Professor of Pulmonary and Critical Care Medicine; Associate Professor of Microbiology and Immunology; Associate Fellowship Director, Pulmonary and Critical Care Medicine

Anna Schwendeman, PhD

Larry and Ann Hsu Professor, Professor of Pharmaceutical Sciences and Chair, Department of Pharmaceutical Sciences, College of Pharmacy

Kathleen Stringer, PharmD Albert B Prescott Professor of Clinical and Translational Pharmacy; Professor of Internal Medicine

WEIL INSTITUTE 2024 YEAR IN REVIEW Through the support of Weil Institute resources such as our Core Teams and Grand Challenges, our members were able to obtain research funding totaling:

$22,412,073

in grants suppo rted by our Proposal Developm ent Team were funded in 202 4.

$1,088,736 in total research funding was awarded in 2024 through our Massey and Kahn Grand Challenge events.

CATCHING UP WITH...

The Great Lakes Clinical Center of the ARDS, Pneumonia & Sepsis Phenotyping Consortium

Researchers team up to improve our understanding of APS conditions and study their impact on disease development, trajectory & outcomes.

In 2023, through the support of a $3 million grant from the National Institutes of Health (NIH), a team of Weil Institute investigators led the establishment of the Great Lakes Clinical Center of the NIH APS Phenotyping Consortium to improve our understanding of ARDS, pneumonia and sepsis. Together, the four sites of the GLCC—the University of Michigan, Henry Ford Hospital, the University of Cincinnati and the University of Chicago—began collaborating with a nationwide observational study of 5,000 adult patients hospitalized with APS conditions. Alongside the larger study, each site also began its own specific research project, with the University of Michigan focusing specifically on the role of the microbiome in the development, trajectory, and recovery of APS conditions.

Recent Developments

In the past year, the APS Consortium has begun enrolling patients into what will become the largest data and specimen cohort of ICU patients ever collected. The 22-hospital network, for which the University of Michigan is a core clinical center, recently enrolled its 500th out of an anticipated 4,000 patients. In contrast to previous studies, the APS network will collect novel specimens, data, and outcomes, including long-term functional status up to twelve months following discharge.

Weil Institute members hold key roles in the consortium

(From top:) Robert Dickson, MD, is supervising all microbiome sampling and measurements

Interested in using APS data in your research?

Check out the webinar below!

CHECK OUT THE WEBINAR

Hallie Prescott, MD, MSc is supervising all long-term outcomes Andrew Admon, MD, MPH, MS, is chairing the Publications Committee 17

COVER STORY

ANSWERING THE CALL

TEAM SCIENCE IN ACTION AT THE WEIL INSTITUTE

How this institute of interdisciplinary researchers is leading the charge to identify and enable the greatest critical care solutions of our time.

W

e are the Weil Institute, and team science is what we do. Our story began with Dr. Max Harry Weil, a physician, professor and pioneer who envisioned a unique space in which critically ill and injured patients could receive around-the-clock monitoring and care from a multidisciplinary team of health professionals. This would help lay the foundation for what we currently call intensive care units (ICUs) and the specialty of critical care medicine as we know it.

As the Weil Institute, our mission is in lockstep with Dr. Weil’s vision: transforming critical care.

It’s three simple words, but, like the field itself, the goal behind those words is complex and requires teams of all stripes working together. On the following pages, you will see examples of the Weil Institute’s unique brand of team science following a recipe mixed by Dr. Weil himself: innovation, integration and entrepreneurship.

Innovation

Our members are developing hundreds of technologies and therapies that redefine what we know as critical care. These are solutions that will diagnose patients sooner, treat them faster and more safely, and extend care outside the physical walls of the hospital—ensuring patients get exactly what they need in the seconds, minutes, and hours following a medical emergency.

Integration

We are strategically integrated throughout U-M to connect all types of critical care providers with basic scientists, engineers (including chemical, mechanical, electrical, biomedical, etc.), computer and data scientists, and many others. We also provide these teams with essential support services that enable them to quickly and effectively take their ideas from concept to reality.

Entrepreneurship

Our ideas are informed and infused with serious entrepreneurship and commercialization expertise at very early stages, making our ability to develop new companies and work with industry partners a key ingredient to saving lives.

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Dr. Kenn Oldham (right), Associate Director of the Weil Institute and Professor of Mechanical Engineering, gathers data for his Massey TBI Grand Challenge-funded project.

Dr. Oldham’s device uses a motion sensor placed on the closed eyelid to measure changes in the frequency response of eye vibration as potential indicators of increased intracranial pressure. The team aims to determine if these ocular acoustic resonance measures could provide a noninvasive method for estimating intracranial pressure.

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1. Physician, Professor, Pioneer Our namesake: Dr. Max Harry Weil. In the late 1950s, he and fellow cardiologist Dr. Herbert Shubin established the Shock Ward at Los Angeles County-USC Medical Center—a unique space where patients could be looked after 24 hours a day by interdisciplinary teams of health professionals. This would help lay the foundation for what we currently call the ICU and the specialty of critical care medicine. Dr. Weil also owned more than 20 patents for medical equipment and devices he developed to help monitor and treat critically ill patients. Many of today’s strategies for managing the critically ill are built on foundations he and his colleagues put in place.

2. Easing the Mental Burden of a Medical Emergency

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It can be difficult for a patient’s family to understand everything that is happening to their loved one, and decisions around care can be difficult for families to make given misinformation and the confusing, rapidly evolving nature of a medical emergency. Developed in a collaboration between the Weil Institute and Elm Park Labs, an Ann Arbor-based software development company, “Care Companion” lets users explore, learn about, and interact with the ICU through augmented reality. The app eases uncertainty for families by providing answers to common questions about the ICU technologies and care team members who are supporting their loved one. The information provided in the app also supports clinical staff by augmenting some of their patient education duties.

3. A Heart-Saving Solution through Data, Engineering & Medicine Dr. Sardar Ansari (center), Data Science Team Lead at the Weil Institute and Assistant Professor of Emergency Medicine, presents an early prototype of the VATMOS wearable sensor to members of the Michigan Medicine Dean’s Advisory Group. Worn like a ring, VATMOS non-invasively measures the reactivity of the smaller blood vessels in the finger to detect potential cardiac events. The device, which was recently awarded a $1 million grant from the American Heart Association, is the result of the combined efforts of Weil Institute engineers, data scientists and clinicians.

4. Weil Grand Challenges Unite Different Disciplines Weil Institute Grand Challenges are powerful funding mechanisms uniquely focused around supporting multidisciplinary critical care research teams. From left: Dr. Nathan Haas, Clinical Assistant Professor of Emergency Medicine, and Dr. Katharine Seagly, Clinical Associate Professor of Physical Medicine and Rehabilitation share updates on their Massey-funded project at the Massey TBI Regional Conference.

Their work studies how changes in blood sugar contribute to the progression and outcomes of secondary brain injury. All Massey Grand Challenge teams funded in a particular year are invited to show posters of their work at the subsequent Massey Regional Conference or Summit, where they will be able to network with and receive feedback from the various other experts in attendance.

5. Data & Engineering Enhance Brain Pressure Monitoring Accurate intracranial pressure (ICP) monitoring is vital to evaluating and treating TBI in the early hours of care. To do so, caregivers currently use devices called external ventricular drains (EVD), yet these systems must be adjusted manually and cannot take real-time measurements. Developed by Dr. Rodney Daniels, Scientific Director of the Kahn Grand Challenge and Professor of Pediatrics and Biomedical Engineering, the Digital External Ventricular Drain (DEVD) automates this process, incorporating data analytics to provide accurate, real-time ICP and cerebrospinal fluid (CSF) flow measurements while also monitoring patient position and providing real-time alerts to caregivers when changes occur.

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6. Lived Experience Empowers Research Efforts Members of the Massey TBI Lived Experience Advisory Board with special guest Bob Woodruff (far right) at the 2024 Massey TBI Summit. The Lived-Experience Advisory Board is a new inititative forged from ongoing partnerships between the Weil Institute and the patients we invite to share their experiences.

These unique subject-matter experts will become a vital resource for Weil Institute researchers. From left: brothers Matthew and Ryan Finneran, Guy Boyd and his mother Denise Wieck, and Ryan Shami.

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7. The Clinical Research Team Assembles

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Members of the Weil Institute Clinical Research team at the 2024 Massey TBI Summit. Many U-M investigators attending the Summit—as well as many other Weil events—are, or will be, actively working with this team to move their research into the hospital for trials with patients. (From left:) Shalini Kota, former Clinical Research Coordinator; Sai Likhita Mamillapalli, Clinical Research Coordinator; Solomon Song, former Clinical Research Coordinator; and Justin Yates, PhD, Research Area Specialist Sr.

8. Predictive Analytics Enhance Outcomes in Kids and Adults The Weil Institute’s PICTURE is a suite of machine learning algorithms that uses electronic health record data to predict patient deterioration in hospital settings. On average, PICTURE predicts deterioration an average of 30 hours in advance of the event, enabling clinicians to intervene early.

Together with a model geared toward adult patients, the Weil Institute has also developed a model specific for pediatric patient populations that is modeled after a separate data set and takes into account several features determined by Michigan Medicine pediatricians.

9. “Not Just Small Adults”: The Pediatrics Perspective Dr. Rodney Daniels leads a panel discussion on innovation and commercialization during the 2025 Kahn Pediatric Critical Care Grand Challenge kickoff. Research, medical, and technology development specialists will be quick to tell you that pediatric patients cannot be looked at as simply “small adults.”

They are a unique population all their own and have specialized needs. Expert panel discussions like this provide key insights to Weil researchers across disciplines who are looking to innovate in this space.

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10. Industry and Academia Re-envision the Tourniquet In 2019, the Weil Institute and its partner, Precision Trauma, LLC., developed the Turn-i-Kit, a userfriendly and comfortable alternative to the traditional tourniquet that is suitable for users of all ages.

It has a wider band to distribute pressure more evenly, reducing pain and minimizing the risk of nerve damage, and allows for precise tightening to ensure effective bleeding control with less discomfort. In 2023, over 780 were donated to support emergency care providers in Ukraine.

11. Research Meets Commercialization From left: Dr. Jeremy Nelson, Director of Physical Sciences Licensing at Innovation Partnerships, and Dr. Xudong (Sherman) Fan, Richard A. Auhll Endowed Professor of Engineering, speak during the 2024 Kahn Grand Challenge kickoff event. The Weil Institute works closely with the IP and commercialization specialists at Innovation Partnerships to provide our members with resources and expertise that will help them navigate the trials and tribulations of getting their research to the market.

12. Team Science at the Federal Level

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The Weil Institute’s longstanding partnership with the Department of Defense has catalyzed innovation across trauma and combat casualty care. Picture here, Dr. James B. Phillips (second from left), Neurotrauma Portfolio Manager for the Combat Casualty Care Research Program of the US Army Medical Research & Development Command (USAMRDC) speaks at the 2023 Massey TBI Regional Conference. Dr. Phillips also applies his expertise as a member of the “Wolverine Den” that judges Grand Challenge projects.

13. Weil Recognized for Pioneering Partnerships and Innovations At the 2024 Celebrate Invention event, Dr. Kevin Ward, Executive Director of the Weil Institute and Professor of Emergency Medicine and Biomedical Engineering was recognized as the Distinguished University Innovator of the year. From left: Dr. Sridhar Kota, Professor Emeritus of Mechanical Engineering and Herrick Professor Emeritus of Engineering; Andrew Malcolmson, CEO of Fifth Eye—a Weil Institute spin-off company; and Dr. Kelly Sexton, Associate VP for Innovation Partnerships and 23 Economic Impact.

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A DATA SCIENCE SOLUTION FOR A CRITICAL SUPPLY CRISIS When a devastating hurricane causes a national shortage of IV fluids and supplies, the Weil Institute Data Science Team joins forces with AI & Digital Health Innovation to rapidly develop a solution.

Following the devastation of Hurricane Helene in late 2024, Baxter International Inc., the nation’s largest supplier of intravenous (IV) fluids and dialysis solutions, was forced to temporarily halt production and distribution at its plant in North Cove, North Carolina. As a result, healthcare systems across the United States, including U-M Health, began taking immediate measures to identify and reduce their use of IV fluid bags and other Baxter products that were at risk of running out.

Dr. Hitinder Gurm, Chief Medical Officer of U-M Health, Park Willis III Collegiate Professor of Cardiovascular Medicine, and Weil Institute member, together with leadership in Supply Chain Services, recognized the potential for data to guide a timely and proactive response to this critical shortage and sent out a call to rally specialists across the University.

As part of this institution-wide effort, Dr. Brahmajee Nallamothu, Co-Director of AI & Digital Health Innovation (AI&DHI), Professor of Cardiovascular Diseases, and a member of the Weil Institute, reached out to Weil’s Data Science Team to see if they could lend their expertise.

The result? A novel projection model that would help U-M Health leadership make critical and timely decisions around conservation of crucial medical supplies.

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“This was an urgent, yet complicated, situation involving different volumes of fluid bags and a high potential of risk to our patients,” said Dr. Nallamothu. “We knew that if we could have access to even a modest model of how to use these resources more effectively, it would be incredibly impactful.”

“This was a wonderful example of a multidisciplinary team of clinical stakeholders, supply chain specialists, administrators, and data scientists coming together to answer an operational challenge,” said Dr. Gurm. “It showed the potential for us to answer important questions in a timely manner for the benefit of our patients.”

The model the team developed used data on product orders gathered from the University of Michigan Medical Center, U-M Health Sparrow, and U-M Health West to forecast potential supply shortages in both the short and long term.

The model also provided insight into how soon a product would run out as well as the resupply amount that will be needed to achieve a specified buffer.

Weil Institute data scientists Connor O’Brien and Brittany Baur, PhD, led by Weil Institute’s Director of Data Science and Research Assistant Professor of Emergency Medicine Sardar Ansari, PhD, immediately rose to the challenge. Within 24 hours of the initial meeting with AI &

Digital Health Innovation, they had worked together with Supply Chain Services to connect and synthesize data on product ordering and utilization from across U-M Health’s three main sites and had developed the initial version of their projection model. The team then conducted daily refinements to the model which were made possible, in large part, thanks to data quality enhancements being conducted simultaneously by teams across the health system.

“I am always reminded in times of crisis how the University of Michigan is such a special place,” said Dana Habers, MBA, Chief Innovation Officer at U-M Health.

“We work amongst some of the most gifted and intelligent individuals, but what makes us so powerfully capable is our culture where we all love to come together around a common purpose and tackle challenges as a team!”

Building for Future Shortages As of October 15, the Weil Institute has handed administration of the model over to a team led by Amy Cohn, PhD, AB, Chief Transformation Officer at Michigan Medicine and Alfred F. Thurnau Professor of Industrial and Operations Engineering. Dr. Cohn’s team is working with other teams in Health Information

Technology & Services (HITS) to operationalize “We work amongst some of the most the code and improve its gifted and intelligent individuals, but efficiency and reliability.

Once the immediate IV what makes us so powerfully capable fluid shortage is resolved, is our culture where we come together an additional goal will around a common purpose and tackle be to make the model customizable, enabling challenges as a team!” it to be integrated as a more long-term solution Dana Habers, MBA for potential shortages of Chief Innovation Officer, U-M Health different products from different manufacturers in the near future.

“While I am proud of the Weil Data Science Team, I am not the least bit surprised by their ability to rapidly respond to a crisis like this,” said Kevin Ward, MD, Executive Director of the Weil Institute and Professor of Emergency Medicine and Biomedical Engineering. “This team of talented professionals has an amazing ability to grasp the magnitude of a problem and use their unique data science expertise to offer innovative solutions.”

“I am so proud that AI & Digital Health Innovation and Weil Institute teams continue to demonstrate value by simultaneously generating high quality science that impacts healthcare in general, and by showing how you can practically apply to solve real-world problems,” said Prashant Mahajan, MD, MPH, MBA, William G. Barsan Collegiate Professor and Chair of Emergency Medicine, Professor of Pediatrics and Weil Institute member. “The Weil Institute continues to have impact when the world needed it urgently—from during the Covid-19 pandemic, where they developed interventions that were practical and pragmatic to save lives, to solving today’s IV shortage issues.”

WEIL MEMBERS FEATURED IN THIS STORY

Sardar Ansari, PhD

Hitinder Gurm, MD

Associate Professor, Emergency Medicine Data Science Team Lead, Weil Institute

Chief Medical Officer, U-M Health, Park Willis III Collegiate Professor, Cardiovascular Medicine,

Brittany Bauer, PhD Data Scientist, Weil Institute

Brahmajee Nallamothu

Connor O’Brien

Co-Director, AI&DHI Professor, Cardiovascular Diseases

Data Scientist (former), Weil Institute

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Weil Team’s Culture-Free Tool Expedites Diagnosis of Bloodstream Infections Time is of the essence when treating bloodstream infections (BSIs), yet the current gold-standard workflow for diagnosing these conditions can take up to multiple days due to its reliance on culturing (growing bacteria in a controlled laboratory setting.)

With good outcomes relying on early administration of targeted, pathogen-specific treatments, clinicians urgently need a way of reducing time-to-diagnosis.

Meet RDAP At the University of Michigan Max Harry Weil Institute for Critical Care Research and Innovation, a team of clinicians and engineers, in collaboration with Cleveland State University and start-up company Rapidect, Inc. are developing a rapid, ultrasensitive assay that can accurately detect and identify pathogens in blood without the need for bacteria culturing.

“There is a huge discrepancy in how quickly we need to know the species of bacteria that’s causing an infection and what it’s susceptible to, and how long it takes us to get that information,” said Dr. J. Scott VanEpps, an Associate Director of the Weil Institute, Associate Professor of Emergency Medicine and Macromolecular Science and Engineering at U-M, and one of the developers of the “rapid detection-analysis platform” (RDAP). “Because bacteria are so small, and because some infections have such a small amount of them to detect, we have to first grow enough bacteria in culture in order to find them. We typically start antibiotics and get culture simultaneously, but it could still be 2-3 days before we get the information we need.

Our goal with this platform is to skip all of that and detect the bacteria in the very beginning.”

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In a previous proof-of-concept study, the team applied the device in contrived samples of E. coli in blood and achieved an 84-minute sample-to-result turnaround time in the combined bacteria detection-identification step compared to the current standard of care, which typically requires a 24-48-hour culture first. In antibiotic susceptibility testing, a 204-minute sample-to-result turnaround time was achieved compared to the 16-24 hours needed for culture-based methods.

“RDAP needs 88 minutes to perform the detection-identification step. Considering the 16-plus hours required by the standard lab procedure for this step, RDAP is already a near real-time diagnostic for the screening of specific bacterial species,” said study co-author Dr. Siu-Tung Yau, Professor of Electrical Engineering at Cleveland State University.

More recently, the team performed a clinical comparison of the device with that of current culture-based microbiology testing methods using blood samples obtained from patients at Saint Vincent’s Medical System in Cleveland, Ohio. The cohort contained both positive culture samples (confirmed bloodstream infections) as well as negative culture samples. In this study, the RDAP achieved a diagnostic accuracy of 93.3% and 95.4% for detection-identification and antibiotic susceptibility testing, respectively.

Next Steps for the Device Currently, RDAP can detect eight species of bacteria at once, representing 57% of known BSI-causing pathogens. The team’s next steps will be to continue building the device for additional species.

The researchers envision that by using RDAP to expedite time-to-diagnosis, it will reduce the number of broad-spectrum antibiotics that patients are receiving--many of which can only be administered through an IV. This could then enable the patients to transition to oral antibiotics earlier, decreasing their length-of-stay.

HOW IT WORKS RDAP incorporates a technique called field effect enzymatic detection (FEED), in which a series of ultrasensitive electrodes detect changes in electrical charge that occur when enzymes interact with a substrate (in this case, bacteria).

FEED is incredibly useful in diagnostics as it allows doctors to observe which enzymes are active—the type and amount of which could indicate different medical conditions—and to monitor that activity without needing to see the enzymes.

RDAP combines FEED with a process called intrinsic signal amplification which boosts the electric signal to make it easier to detect.

The combined techniques enable RDAP to find and identify bacteria down to extremely small quantities (4 bacteria per milliliter) without requiring culture.

WEIL MEMBERS FEATURED IN THIS STORY

J. Scott VanEpps, MD, PhD Associate Professor of Emergency Medicine, Michigan Medicine; Associate Professor of Macromolecular Sciences and Engineering, College of Engineering

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Harnessing the Power of Military-Academic Partnerships to Improve Battlefield Medical Outcomes FLORIAN SCHMITZBERGER, MD, MS Clinical Assistant Professor, Emergency Medicine, University of Michigan

First stepping foot into Ukraine in 2022, a country prevented many deaths over the years, however we were freshly at war, was an unfortunately familiar scenario now seeing some unintended consequences: frequently for my colleagues and myself. We brought medical casualties could not have their tourniquets removed in a equipment and experience in conflict regions and the timely fashion in this conflict. An overwhelmed medical hope to make at least some kind of impact. While system, long evacuation lines and a lack of focus on we were able to help in a small capacity, we quickly this issue exacerbated the situation. Our research group realized that the key to improving outcomes lies in that included Dr. Kevin Ward, Executive Director of careful study and targeted interventions. the Weil Institute, published an article titled “Life Over One particularly drastic observation fueled our Limb: Why Not Both? Revisiting Tourniquet Practices curiosity: why were so many more casualties than Based on Lessons Learned From the War in Ukraine” expected losing limbs after relatively minor in the Journal of Special Operations Medicine and have seen injuries? After some deliberation and study, we the direct impact of this and other similar publications. found a likely culprit—the prolonged application of Tourniquet conversion has become a key topic of tourniquets for extremity injuries. instruction, has found its way into clinical practice For decades, tourniquets were touted as the last guidelines and has without doubt helped save limbs, resort, the ultima ratio, when dealing with a severe kidneys and lives. injury. Placing a tourniquet was seen as causing significant damage and was to be avoided if at all possible. In the 1990s, the United States Special Operations Command started studying preventable battlefield deaths, and tourniquets made a much-deserved revival. The Joint Trauma System of the United States Department of Defense has led the way in creating guidelines (CPGs —clinical practice guidelines), that list best practices for battlefield injuries. The propagation of these highly effective guidelines had Photos from Dr. Schmitzberger’s deployment in Ukraine. Left: Ukrainian 28

army medical transport vehicle. Right: The flag of Ukraine.

IN RELATED NEWS

Dr. Schmitzbeger to Help Train Future Elite Combat Medics In 2025, Dr. Florian Schmitzberger was named Medical Director of the Special Operations Combat Medic training program at Hurley Medical Center in Flint, MI. SOCM are among the world’s most elite first-response trauma and medical emergency care providers. They begin their training at Fort Bragg, NC, where they undergo a 36week course designed to progress them from having little to no medical background to understanding and conducting lifesaving care from the point of injury through evacuation.

Based on this preliminary work, our group has been supported by the Department of Defense (DoD) with a Global Health Engagement Research Initiative grant to study clinical practice use and their barriers in a more systematic way. Programs like these are key to strengthening the United States Military by harnessing lessons learned from ongoing conflicts and by partnering with academic institutions to augment the capacity of military medical research. Furthermore, the research conducted is not only beneficial to U.S. warfighters, it also can guide care for our patients at home. Civilian clinical practice guidelines, such as the tactical emergency casualty care (TECC) guidelines reflect tourniquet conversion as a key step for some patients.

How can we harness the power of these relationships in the future? Targeted grant opportunities allow academic teams to work together closely with the military in order to ultimately improve patient outcomes. It allows the DoD to supplement existing capabilities in areas in need of investigation. It may allow for more rapid and flexible research to be conducted. Lastly, publication of results will allow for lessons learned by the military to reach civilian care more quickly and the entire population can benefit from them.

1. https://pubmed.ncbi.nlm.nih.gov/38300880/

As their final requirement for graduation, SOCM students must perform an intense, 30-day clinical rotation at one of the program’s official partner trauma centers.

At Hurley, SOCM students work alongside the U-M physicians who staff the emergency department while rotating throughout other areas that will be vital to their roles. They also ride with local paramedics of the Genesee County Sheriff’s Department.

Hurley Medical Center is one of only a handful of institutions in the country recognized as an official SOCM partner site.

This unique military-civilian relationship was established in 2012 by Dr. Kevin Ward, Executive Director of the Weil Institute.

He had implemented and directed a SOCM training program at Virginia Commonwealth University Medical Center and is also actively involved in the program’s current iteration.

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Toward Realizing the Promise of AI in Precision Health Across the Spectrum of Care This article is a summary of the original, which can be read in its entirety at: https://doi.org/10.1146/annurev-genom-010323-010230.

Large academic medical centers are making remarkable strides in harnessing the power of artificial intelligence (AI) to transform clinical decision-making, particularly in the realm of secondary and tertiary care. However, to fully unleash AI’s potential and elevate patient outcomes across the entire healthcare spectrum, we must confront a myriad of challenges. Among these are the uneven application of preventive care and the gaps in managing chronic conditions that hinder progress.

Precision health, a revolutionary concept, encompasses the promise of precision medicine and proactive prevention. Yet, the majority of AI applications in healthcare have been somewhat opportunistic, focusing primarily on well-defined problems within inpatient settings where data is abundant. Outside these environments, the data collected has often been sparse, providing only snapshots rather than comprehensive insights into patient journeys.

There is hope on the horizon, as integrating additional data from genomics and wearable technology offers a powerful avenue for refining AI-driven clinical decision-making. However, this path is not without obstacles, as it must navigate technical, legal, and ethical challenges that need our attention.

On the technical front, merging diverse data types— like genetic information, medical imaging, wearables, and electronic health records—requires sophisticated algorithms that can unveil complex relationships and patterns. Moreover, the scarcity of certain crucial data can challenge the accuracy and trustworthiness of our AI models, calling for innovative approaches to ensure reliable decision support. Healthcare data is primarily gathered during patient interactions for clinical purposes rather than research, so careful consideration of selection bias and confounding factors is vital for making principled inferences.

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Simultaneously, as we move forward, it’s essential to embrace the legal and ethical considerations that arise at the intersection of AI and healthcare.

AI holds tremendous potential to utilize patient data for informed clinical decisions, but we must remain vigilant against the risk of widening existing healthcare disparities. By ensuring representative data collection and implementing AI tools thoughtfully, we can protect vulnerable populations from disproportionate impacts and strive for equity in healthcare outcomes. Principles of data equity and justice are critical to achieving fair decision-making for all.

With the emergence of large language models (LLMs), we stand at the edge of a new era, filled with excitement about the possibilities that generative AI brings to healthcare. However, to realize the successful integration of AI into our clinical decision-making frameworks, we must adopt a holistic and inclusive approach. By addressing the legal and ethical dilemmas that accompany AI implementation, we can pave the way for a future where equitable healthcare is attainable for everyone.

For the last decade, researchers at the intersection of AI and health have dedicated their efforts to secondary and tertiary care centers, driven by a sense of purpose. This focus, however, stems from a practical standpoint—these environments represent fertile ground for collecting extensive patient data, meticulously recorded in electronic health records (EHRs). These troves of data form the cornerstone for machine learning (ML) models that are essential for advancing disease classification, risk prediction, and personalized treatment recommendations.

In disease classification, AI has made inspiring advancements across a spectrum of healthcare challenges, empowering innovations like automated

AUTHORS OF ORIGINAL ARTICLE

From left: Jenna Wiens, PhD (Associate Professor, Computer Science & Engineering; Weil Institute Member); Kayte Spector-Bagdady, JD, MBE (Associate Professor, Obstetrics & Gynecology); Bhramar Mukherjee, PhD (Adjunct Professor, Biostatistics)

tools that detect malignant skin lesions and pioneering diagnostic systems for diabetic retinopathy. The journey from the first explorations of deep learning in healthcare to the current state of market-ready tools in clinics reflects significant progress and determination.

When these groundbreaking tools are thoughtfully integrated into existing workflows, they can liberate precious time for clinicians, enabling them to focus on what truly matters—their patients. Many of the most noteworthy successes have emerged from settings where clinicians are already excelling, further demonstrating that with AI, we can enhance existing capabilities and strive for excellence together.

Recently, the focus has also shifted toward using deep learning to empower clinicians in tackling challenging clinical scenarios. For example, researchers are dedicated to addressing the complexities surrounding acute respiratory failure, a condition that often leaves healthcare providers grappling for answers. This serious condition is tied to substantial health challenges and costs, with several underlying causes, including heart failure, pneumonia, and chronic obstructive pulmonary disease. Identifying the root cause is not just a task— it’s a mission to ensure effective treatment and better outcomes for all patients.

Organizations implementing AI solutions must carefully consider how they can improve care for all and reduce inequities. Together, we embark on this journey, fueled by hope and ambition, toward a future where healthcare is equitable, accessible, and powered by innovation.

Annual Review of Genomics and Human Genetics, Vol. 25:141-159 (Volume publication date August 2024) https://doi.org/10.1146/ annurev-genom-010323-010230 First published as a Review in Advance on May 09, 2024.

Copyright © 2024 by the author(s).

Leveraging Health AI Resources at U-M: Collaborating with Partners The Weil Institute values strategic partnerships with U-M’s AI & Digital Health Innovation (AI&DHI) and the Michigan Institute for Data & AI in Society (MIDAS) to maximize the “collaborative advantage” as a strategy for moving our AI research from the bench to the bedside.

Funding from MIDAS has helped launch several key research projects for our members, while AI&DHI provides de-identified health data and implementation strategies for testing research at Michigan Medicine.

The operational support provided through these collaborations enables our members to remain focused on their areas of expertise, allowing them to complete their research effectively.

“The Weil Institute houses some of U-M’s foremost experts in using AI to improve critical care. The AI & Digital Health Innovation team is excited to support them in developing research across a range of AI-enabled solutions, including wearables and performance monitors.”

Brahmajee K. Nallamothu, Co-Director, AI&DHI; Stevo Julius Research Professor of Cardiovascular Medicine; Professor of Internal Medicine; Program Director, Michigan Center for Healthcare Analytics and Medical Prediction (M-CHAMP); and Weil Institute member

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How Weil Grants Benefit Patients

KEVIN WARD, MD Executive Director, Weil Institute; Professor, Emergency Medicine and Biomedical Engineering

KATHLEEN STRINGER, PHARMD Deputy Director, Weil Institute; Albert B. Prescott Collegiate Professor, Clinical & Translational Pharmacy

ROBERT DICKSON, MD Deputy Director, Weil Institute; Galen B. Toews Legacy Professor, Pulmonary & Critical Care Medicine

MEAGAN RAMSEY, PHD Director, Weil Institute Proposal Development Unit

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Critical illnesses and injuries are the silent epidemic of our country.

These conditions involve sudden, severe medical emergencies that require immediate, high-level care to prevent death or permanent organ damage. Each year, more people die from critical illness or injury than cancer or heart disease.

Even when a patient’s life can be saved, critical illnesses and injuries pose a huge cost to them and their families.

Approx.

6 Million

$260b

Number of patients admitted to U.S. ICUs each year

Annual costs for hospitals (up to 40% of all hospital costs)

More than

Up to

$4k

50%

Cost per day to an individual patient in the ICU

Amount of ICU survivors who never return to work.

Critical illnesses and injuries can happen to anyone and at any time.

A family with young children is involved in a serious car accident, and the closest hospital is over an hour away.

Paramedics need the right tools to keep every family member alive during ambulance transport no matter what types of injuries they each have, ensuring they make it to the hospital for more advanced treatments.

A Veteran suddenly develops sepsis, a life-threatening response to an infection that causes systemic inflammation.

There is currently no cure for sepsis; it can only be treated supportively. The Veteran may be in the intensive care unit (ICU) for over a week. Doctors need better treatments to make sure that these patients recover.

A manager’s heart suddenly stops beating, causing them to go into cardiac arrest while they are at the office.

They could be quickly revived if co-workers have the right tools while waiting for an ambulance.

Early use of CPR is critical for preventing brain damage.

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The Weil Institute is changing the landscape of critical care through grant-funded projects.

We have united more than 270 doctors, scientists, engineers, and entrepreneurs to create life-changing technologies and treatments that will allow us to diagnose patients sooner, treat them faster and more safely, decrease the number of days a patient must spend in the ICU, restore patient health faster after critical illness and injury, minimize the devastating costs to patients and families, and substantially reduce preventable deaths.

In just 10 years, we have developed solutions such as...

The world’s most advanced animal models of sepsis, severe lung injury, TBI, and cardiac arrest—required to get solutions to patients faster

One of the most advanced data science and artificial intelligence (A.I.) operations across the field and spectrum of critical care medicine

A breathalyzer that predicts the onset of acute lung diseases using only a sample of the patient’s breath (works with ventilators, too!)

Glasses that measure brain pressure (which is otherwise measured by drilling a small hole in the patient’s skull)

A simple and more effective tourniquet that anyone can use to stop bleeding, even without training

A low-cost “helmet” that uses light to prevent brain damage after cardiac arrest

A small abdominal balloon that can halt catastrophic internal bleeding at the scene of an accident

A helmet worn by patients with transmissible respiratory diseases to keep other patients and families safe

A.I. systems to predict and help prevent the onset of sepsis and insufficient blood flow to vital organs

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Critical care solutions like these could not have been developed without federal grants & indirect funding.

Cutting-edge research leads to better treatments, which saves lives and reduces the enormous burden of critical illness and injury on patients and families.

Direct grant funding supports the scientific work required to develop and test these lifesaving technologies and treatments. Indirect grant funding is what makes this research possible. It provides the critical infrastructure and expertise needed to turn ideas into realworld medical solutions.

Indirect grant funding supports: Pre-grant Research and Preparation This includes generating preliminary data to demonstrate a project’s value and determine if a project is worthy of federal dollars. This critical groundwork¬—such as study design, data collection, and regulatory planning—is performed by administrative and research staff and is supported by indirect grant funding.

Essential Infrastructure Needed for Research Infrastructure includes ensuring regulatory oversight, patient and animal safety, and responsible fiscal management of federal funding. Infrastructure also includes financial support for the specialized laboratory space where the research will take place.

Translating Discoveries into Real Solutions Most doctors and researchers lack the expertise to navigate medical product licensing and commercialization. Without this, federally funded breakthroughs would never reach the patients who need them.

What will happen if the government’s proposed reductions to biomedical research funding take effect?

If indirect costs are reduced, the Weil Institute will be forced to lay off many highly skilled personnel, immediately jeopardizing patient lives and wasting prior federal investments. Reductions in funding will also cause critical research around the nation to stall, delaying or halting life-saving technologies for our sickest patients. They will also result in life-saving technologies being stranded in development, wasting federal investments and denying patients needed treatments.

Donate to the Weil Institute

PERSPECTIVES

Weil Data Scientists Discuss: Challenges in Post-market Monitoring of Clinical Prediction Models In a perspective piece published in the New England Journal of Medicine – AI, data science researchers and members of the Max Harry Weil Institute for Critical Care Research and Innovation share their thoughts on the current challenges of monitoring predictive artificial intelligence (AI) models deployed in clinical settings.

“AI models can greatly enhance clinical workflows, including the diagnosis and prognostication of various conditions, yet they suffer from post-deployment performance degradation due to factors such as changes in the patient population, clinical practice or data mapping, to name a few,” said publication author Dr. Sardar Ansari, Assistant Professor of Emergency Medicine and Director of Data Science at the Weil Institute.

In the piece, Dr. Ansari and co-authors Dr. Brittany Baur, Dr. Karandeep Singh and Dr. Andrew Admon discuss several previously proposed methods for post-market AI model surveillance. They note that while these solutions each have their strengths, none can estimate the performance of the predictive AI models after deployment. This can lead to models that cannot be later evaluated, tuned, or withdrawn if they become ineffective, leading to potential patient harm.

As an alternative, the authors propose that approaches based on advanced causal modeling may offer reliable validation methods that are less susceptible to the challenges faced by other methods. According to co-author Dr. Andrew Admon, the key to this approach involves separately considering the effects of the AI model’s recommendation on clinical decisions and the effects of these decisions on the predicted outcomes.

If a model’s degraded performance over time is driven by clinicians acting on model predictions to avert adverse outcomes, validating models against counterfactual outcomes—outcomes that would have occurred had a clinician not intervened—may enable consistent post-deployment validation despite effective interventions.

- Andrew Admon, MD, MPH, MS

AUTHORS OF ORIGINAL PUBLICATION

Sardar Ansari, PhD Assistant Professor, Emergency Medicine; Director of Data Science, Weil Institute

Brittany Baur, PhD Assistant Research Scientist, Emergency Medicine; Senior Data Scientist, Weil Institute

Karandeep Singh, MD, MMSc Joan and Irwin Jacobs Chancellor’s Endowed Chair, Digital Health Innovation; Chief Health AI Officer, UC San Diego Health

Andrew Admon, MD, MPH, MS Assistant Professor, Internal Medicine and Epidemiology; Member, Weil Institute

VIEW ORIGINAL PUBLICATION Ansari, S., Baur, B., Singh, K., & Admon, A. J. (2025).

Challenges in the Postmarket Surveillance of Clinical Prediction Models. NEJM AI, 2(5). https://doi.org/10.1056/ aip2401116

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