Search

Introduction. The transition to exploration missions places a heightened risk on behavioral health in spaceflight. Although serious psychiatric emergencies during spaceflight have been rare, longer duration missions increase the possibility of emergence in latent mental health disorders due to genetic predisposition, increased autonomy, isolation, helplessness, loss of family member, or catastrophic events. Complicated grief and bereavement have the highest rate of suicidal ideation. Recently, ketamine has been used as an emergent intervention for acute suicidality, promoting its stability, ease of administration, favorable safety profile, and outcomes for reduction of suicidal intent. The goal of this study was to review current literature and collate the understanding of ketamine as a safe, effective pharmacological adjunct for acute suicidality in spaceflight. Methods. This literature review was conducted to collate data on ketamine use for acute suicidality and inform on stability, limitations and utilization of ketamine within extreme environments. Results. 122 publications were reviewed for relevance including 23 randomized-control trials for ketamine use in behavioral emergencies. Discussion. Ketamine is a diverse pharmaceutical with multiple advantageous indications, including acute suicidality, pain, and sedation. Terrestrial use of ketamine suggests a rapidly efficacious medication for reduction in acute suicidality. As behavioral stressors expand related to extended missions, contingencies for behavioral emergencies become increasingly important. Although this review is not intended to re-develop current International Space Station (ISS) protocols, it is the first to discuss the benefits of ketamine in spaceflight as a potential safe, effective multifaceted tool for future exploration missions and treatment for acute suicidal ideation.

NASA is working with industry and international partners to return humans to the Moon and to eventually enable humans to explore Mars. Within NASA, several organizations work together to identify, prioritize, fund, execute, and operationalize the research and technology development (R&TD) that will be necessary to enable crew health and performance (CHP) during these future missions. These organizations include flight programs, the Health and Medical Technical Authority (HMTA), the Human Research Program, the Space Technology Mission Directorate, System Capability Leadership Teams, and other organizations, many of which existed for several years prior to the creation of the Moon-to-Mars (M2M) Program Office in 2023. A variety of constructs, vocabularies, and processes exist for managing risks and supporting strategic planning across these organizations. For example, M2M objectives, program risks, human system risks, human research gaps, capability gaps, and envisioned futures are all constructs currently used within NASA to identify and prioritize R&TD needs. These strategic planning constructs are evolving to allow M2M objectives and R&TD investments to be aligned and traced at a detailed level. A recognized need exists among stakeholder organizations to identify and communicate the highest CHP R&TD priorities in a unified and digestible way that addresses the perspectives of NASA’s CHP community. To achieve this, the HMTA arranged a series of discussions with representatives of NASA’s CHP community, during which the 8 highest priority CHP capabilities that will enable human missions to Mars, referred to as the “top human system capability needs for Mars”, were identified. The list includes Earth-independent human operations; Mars-duration food system; Mars-duration effects on human physiology; risk mitigations for vehicle atmospheres; computational injury and anthropometric models; exploration exercise countermeasures; individual variability in responses to spaceflight; and sensorimotor countermeasures. Existing tools and processes for strategic planning and risk management were evaluated, as well as the technical practicalities, cost, and schedule feasibility associated with potential R&TD investments in different capability need areas. This capability needs report is not owned by any one NASA organization and does not replace existing strategic or program planning processes; rather it aims to complement and inform them with a unified set of community generated priorities. These top capability needs will be re-evaluated periodically based on R&TD progress and the evolving M2M architecture.

BACKGROUND NASA’s human exploration spaceflight missions to the Moon and Mars present unprecedented challenges for in-mission medical care. A greater distance from Earth will mean increased mission durations, communication delays, limited to no resupply opportunities, and constraints on the evacuation of ill or injured crew. Mass, volume, and power will be limited while higher demands will be placed on the crews to manage medical events. NASA’s Moon to Mars exploration strategy outlines increasingly complex Artemis missions both in terms of duration and operations. In these more challenging deep space missions, it is important to quantitatively estimate the human system risk attributable to medical conditions and use these estimates to advance medical system design. METHODS IMPACT (Informing Mission Planning via Analysis of Complex Tradespaces) is a probabilistic risk assessment (PRA) and tradespace analysis tool developed by NASA to advance exploration mission medical system design. IMPACT v1.0 includes a novel evidence library baselined to exploration environments; an expanded list of 119 medical conditions; a large increase in the number of medical resources and the flexibility of their use; and the ability for rapid and iterative analysis. Medical system risk estimates include loss of crew life, consideration of the need for return to definitive care (medical evacuation), and an estimate of crew time affected due to medical conditions. A notional long duration lunar orbit and lunar surface design reference mission (DRM) was chosen with a 4-astronaut crew to mimic a foundational exploration Artemis mission. The DRM profile includes outbound transit on Orion, Gateway space station rendezvous in lunar orbit, 6 months on the Lunar surface with extravehicular activity (EVA), return rendezvous with Gateway, and transit back to Earth. RESULTS/DISCUSSION: Overall, IMPACT successfully quantified medical risk and derived an optimal medical system to support crew on a long duration lunar mission. In this DRM, the calculated loss of crew life from a medical event was 0.008 events per mission, risk of potential need for evacuation was 0.30 events per mission, and cumulative crew time affected by medical conditions was 103 days. The medical conditions that most contributed to medical risk were decompression sickness, trauma, and respiratory failure. The conditions that had the largest effects on crew performance included musculoskeletal injuries and lunar dust exposure. The IMPACT-generated medical system included resources that target the most common and highest risk conditions and performed as expected. This demonstrates the value of the IMPACT tool in medical system design for human exploration spaceflight missions.

The Space Radiation Element (SRE) with the Human Research Program (HRP) and NASA is tasked with the mission of characterizing and facilitating the management of the human health outcomes associated with space radiation exposure to ultimately protect astronaut health as well as enable human space exploration. To facilitate our mission, we provide funding for space radiation research but also provide several unique opportunities discussed below to educate and disseminate space radiation knowledge.

To enable deep space exploration and sustained human presence in space, the NASA Human Research Program’s (HRP) Space Radiation Element (SRE) funds research to characterize and mitigate adverse health outcomes from exposure to space radiation that include risks of carcinogenesis, cardiovascular disease, and central nervous system decrements. Recently, the SRE was tasked with supporting multiple HRP Elements with innovative and enabling projects to inform risk characterization, facilitate mitigation activities, and support crew health and performance. These projects, such as precision health initiative, NASA Omics Archive (NOA) and human sample repositories, are agnostic to any HRP Element, hence the name, Cross-Risk Integration Projects (CRIP). CRIP serves 3 broad purposes: - Services: Generate samples and data and manage the receipt, inventory, archive, and ultimate redistribution of biospecimens created in HRP-funded spaceflight and analog research activities—includes NASA Omics Archive project and various human and animal sample repositories. - Method Development: Identify and evaluate new-to-NASA research or analysis methods or techniques that could fundamentally improve existing or planned research efforts—includes the Translational Radiation Research and Countermeasures Project. - Enabling Capabilities: Demonstrate real-world application by adapting, adopting, and/or developing capabilities to benefit crew health and performance and improve risk mitigation—includes Precision Health Initiative (Pharmacogenomics) and advanced biological systems and engineered tissue microsystems initiative (tissue chips, organ-on-a-chip). To identify new technologies, future work, and solicitations, the SRE organizes themed sessions at annual HRP Investigators’ Workshops (IWS). These technical interchange meetings (TIMs) provide a venue for the scientific community to present ongoing work and engage in open discussion of results, limitations of current approaches, and incorporation of novel experimental strategies, model systems, and other innovative techniques. Here, a summary of the studies presented at the SRE-sponsored mini-TIM at the HRP IWS along with the goals and objectives of the CRIP projects is communicated. The 90-min TIM had 6 speakers who presented impressive novel ideas and work, some of which are funded under CRIP by the Space Radiation Element.

Throughout the history of human spaceflight, crewmembers have experienced various in-flight medical conditions including illness and injury. Planned missions to the Moon and Mars will require capabilities to maintain the health of future space travelers. Mass, power, and volume available in the vehicles and habitats for these missions will be severely constrained; resupply of resources will be limited or non-existent, as will opportunities for evacuation to Earth. Furthermore, ground-based support will be hampered by communication latencies and blackouts. These vehicle and mission constraints will necessitate a medical system that has been efficiently planned, providing on-board procedural guidance in addition to a variety of medical devices and consumable resources. Medical capabilities required for the diagnosis and treatment of potential medical conditions during future spaceflight missions may include real-time health monitoring, medical imaging, and biomarker analyses ( e.g., blood or urine). Terrestrial medicine shares these needs, thus many of these medical capabilities could likely be satisfied by Commercial-Off-The-Shelf (COTS) devices and methodologies; however, in some cases the unique space environment and increased mission duration will drive the need to modify technologies and the way care is provided. NASA’s Human Research Program (HRP) Exploration Medical Capability (ExMC) Element and Mars Campaign Office’s Exploration Medical Integrated Product Team (XMIPT) are working together to decrease medical risk during exploration missions. Flight-tested medical diagnostic and treatment technologies are necessary to effectively manage medical conditions relevant to exploration missions while meeting vehicle constraints, integrating with medical decision-support tools, and enabling increasingly Earth-independent operations. Several projects have leveraged the ISS as a testbed for exploration, including 1) i n- situ blood analysis, 2) medical inventory, 3) intravenous fluid generation, and 4) autonomous medical procedure guidance. Management of several in-flight medical conditions, such as bacterial and viral infections and acute radiation syndrome, is dramatically improved with ability to assess blood cell populations, electrolytes, and metabolites. I n December 2020 and January 2021 ExMC performed an ISS technology demonstration (Tech Demo) of the HemoCue® WBC DIFF analyzer (HemoCue, Brea, CA), a COTS device that was modified to enable functionality in a spaceflight environment. This Tech Demo marked the first time that hematology measurements were successfully performed real-time in microgravity. Also modified and demonstrated was the reusable Handheld Electrolytes and Lab Technology for Humans (rHEALTH) ONE analyzer (rHEALTH, Bedford, MA), which uses flow cytometry and sheath-based hydrodynamic focusing methodologies. The rHEALTH ONE ISS Tech Demo in May 2022 demonstrated test results obtained in-flight matched those on the ground. NASA currently relies on crew self-reporting to manage and maintain medical inventory on ISS.The ability to maintain an accurate inventory becomes more critical during long duration missions since the crew will need to be increasingly autonomous in finding and utilizing medical items, including those scenarios when alternative treatments need to be considered due to limited or no resupply. HRP’s Medical Consumables Tracking (MCT) project was developed by ZIN Technologies, Inc. (Cleveland, OH), and demonstrated real-time tracking of medical supplies aboard the ISS between December 2016 and July 2018. The MCT system design utilized Radio Frequency Identification Device (RFID) technology to perform automated inventory and was installed in the Crew Health Care System (CHeCS) Resupply Stowage Rack (RSR). The challenge of limited shelf life, exacerbated by the lack of resupply opportunities, affects a plethora of medical system components including consumables, pharmaceuticals, and intravenous (IV) fluid. In 2010, ExMC funded ZIN Technologies, Inc. (Cleveland, OH), to develop the Intravenous Fluid Generation (IVGEN) system. IV fluids were successfully generated with IVGEN using the potable water supply on ISS during ISS Expedition 23. The XMIPT is in the process of developing a miniaturized version of the original IVGEN hardware for a future Tech Demo aboard the ISS. Current ISS medical operations rely heavily on preflight training and real-time remote guidance, both of which become impractical or impossible for exploration missions. The primary goal of the Autonomous Medical Officer Support (AMOS) Software Tech Demos on ISS was to confirm telemedical proof-of-concept for autonomous medical imaging in an operational setting. This novel software tool shifts emphasis from preflight training and real-time remote guidance to in-flight just-in-time instruction, a new and necessary paradigm for crew medical autonomy. AMOS introduces a novel, streamlined skill management concept for exploration missions featuring comprehensive training and guidance modules for ultrasound examinations using the ISS Ultrasound 2 (a modified GE Vivid-q™; General Electric HealthCare, Chicago, IL). With no prior crew training or remote guidance, two Tech Demos on the ISS (April 2020 and June 2022) resulted in high quality, clinically useful image sets. We will provide a review of historical, current, and planned medical devices and technologies considered for inclusion within future spaceflight medical systems and summarize hardware development activities and medical device tech demos conducted on the ISS.

Long duration spaceflight missions will require crew to become more autonomous in conducting extravehicular activities (EVA) without direct communication with Mission Control for biomedical support. To enable such autonomy, we are developing a Crew State and Risk Model (CSRM) as a collection of key physiology domains that drive EVA crew capabilities and workloads. One model component of CSRM is human thermal regulation. In this paper, customized development of a baseline model to predict core body temperature is presented using physiology inputs of heart rate and metabolic rate. The model development dataset included a baseline study where participants (n=6, equal male and female) performed a 5-hour EVA in a two-part session while wearing a hybrid space suit simulator (HS3). The first session included an end-to-end EVA traversing 1500 meters to a geology site and traversing back to a habitat conducting geology, payload relocation, and maintenance operations every 500 meters. The second session included standalone tasks of a 2000-meter traverse followed by geology tasks. Thermal measures of core body temperature, local skin temperature, liquid cooling garment temperature, heart rate, and metabolic rate were collected through the test duration. Multiple regression was used to build a linear equation to predict core body temperature from inputs of heart rate and metabolic rate. Heat storage was calculated via predicted core body temperature plus LCG and skin temperatures. The model was tested against a dataset from a pressurized suited test (n=6, equal male and female) in the NASA Active Response Gravity Offload System (ARGOS) conducting similar end-to-end EVA and standalone tasks. Predicted error of the model against the raw test cases was 0.2±0.15 °C. The baseline prediction of core body temperature using heart rates and metabolic rates allows for simple real-time tracking from data collected in-flight to monitor crew consumables and thermal flight limits during EVA.

INTRODUCTION. Investigation of a central neurological decompression sickness (DCS) case during ground testing at Johnson Space Center identified a break-in-prebreathe (BIP) 13 minutes prior to depressurization as the leading credible cause despite applicable prebreathe payback rules being followed. Applicable NASA rules, for ground and flight, directed 2:1 payback of breaks up to 10 mins in duration, regardless of when a break occurs relative to depress. Full restart of prebreathe is directed following breaks > 10 min. The adequacy of NASA’s BIP rules was evaluated prior to resuming hypobaric ground testing or ISS extravehicular activities. METHODS. The following information sources were reviewed prior to formulating recommendations: i) Type II DCS case report and investigation findings; ii) documented rationale for existing flight rules, iii) consultations with subject matter experts involved in definition of existing flight rules (several of whom had since left NASA), iv) relevant published literature, v) model estimates of tissue on-gassing and off-gassing, and vi) NASA’s operational experience with late breaks in prebreathe. RESULTS. NASA’s nominal prebreathe protocols are validated via extensive ground testing to ensure DCS risk is reduced to within acceptable limits. Conversely, there exists a paucity of data, no validated models, and limited documentation regarding BIP risk for NASA prebreathe protocols. Flight rules implemented for shuttle and later ISS are based primarily on expert opinion and an assumption of symmetric on-gassing and off-gassing, which would make 2:1 payback a conservative mitigation for a BIP. Assumption of exponential gas kinetics makes late breaks higher risk, or require greater payback, than earlier breaks. Two BIPs have occurred using the current ISS prebreathe protocol, each of which was followed by greater than 2:1 payback and at least 59 minutes of 100% O2 pre-depress. No DCS cases have been reported during shuttle or ISS EVA operations. DISCUSSION. Interim changes were implemented to protect against late breaks during ground and flight prebreathes by ensuring negligible difference in conservatively modeled ppN2 pre-depress compared to nominal validated protocols. Additional documentation and literature review as well as chamber test planning are ongoing with the objective of further ground and flight rule updates and validation of a BIP risk model.

BACKGROUND: Radiation, reduced gravity, distance from earth, isolation and confinement, and habitation within artificially created and controlled life support environments are hazards that present risk to human space explorers. NASA’s Human System Risk Board (HSRB) maintains a set of twenty-nine different Human System Risks with subject matter experts from across the agency providing regular updates to the estimated likelihood and consequence associated with each risk. The Human Research Program (HRP) has historically used these risk classifications as a primary basis for identifying and prioritizing human research investments aimed at characterizing and/or mitigating the respective human system risks. In many cases, technology development is required to mature and validate risk mitigation strategies, however, NASA’s primary technology development programs have not typically used Human System Risks as a basis for strategic planning. A primary function of the Environmental Control and Life Support Systems (ECLSS) – Crew Health and Performance (CHP) System Capability Leadership Team (SCLT) is to continually identify, review, and update technological capability gaps and to establish and oversee multiyear strategic roadmaps aimed at guiding NASA’s technology development priorities in these areas. These roadmaps are intended to be agency-wide and independent of any program, directorate, or other organization within NASA. DESCRIPTION: The SCLT and HRP collaborated to establish a set of Human System Capability Gaps, which establish a formal linkage between the capability gaps used to prioritize investments across much of NASA, and the Human System Risks that are primarily used to inform and prioritize human research. This set of twenty-eight gaps was developed by subject matter experts, and each gap mapped to the primary associated Human System Risks. The gaps and risk mapping were then reviewed and approved via the HSRB, thereby formally aligning the research-focused Human System Risks with the technology-focused capability gaps. DISCUSSION: This effort has enabled development of integrated roadmaps and budget coordination with research and technology development activities that are formally linked to agency-recognized capability gaps and Human System Risks. Close and ongoing coordination between the SCLT, HRP, Mars Campaign Office, and the Health & Medical Technical Authority (HMTA) is essential to ensure alignment and prioritization of CHP-related research and technology development to enable NASA’s future exploration missions.

INTRODUCTION: Renal stones are thought to be a risk for spaceflight due to urine chemistry changes, induced by microgravity. Asymptomatic stone can have significant medical and mission impact.For9 years astronauts travelling to the International Space Station (ISS) have received pre-and post-flight renal ultrasound, according to a specialized renal ultrasound protocol, to look for renal calcifications or mineralized renal material (MRM).A new ultrasound machine was put in service halfway through the screening program. METHODS: MRM screening data from pre-and post-flight were compared, to look for changes in MRM burden. Pre-and post-flight scans from 42 subjects were compared. Studies were further stratified by old versus new machine. Measures were modeled using the analysis of variance (ANOVA) as defined by the interaction between pre-to postflight, and machine-to-machine. RESULTS: There was no observed statistical change seen in MRM burden pre-to postflight using the new higher-resolution ultrasound machine. DISCUSSION: The new machine gives more precise measurements and allows us to differentiate MRMs from other bright objects seen on ultrasound, such as small blood vessels. These data imply that spaceflight does not increase the risk of renal stone formation, at least out to the length of ISS missions. This data will be used to update NASA’s Human System Risk Board’s risk tracking documents, in-flight Concept of Operations, and our Clinical Practice Guideline.

Introduction: Hydration is critical for optimal human health and performance and dehydration can lead to impaired cardiovascular function, thermal dysregulation, decreased blood plasma volume, and cognitive impacts, particularly during physical activity. Prolonged and repeated extravehicular activities (EVA) without sufficiently available drinking water may increase risk for dehydration, which could impair crew health and impact mission success. Understanding hydration needs and potential effects on health and performance are necessary to optimize crew well-being and enable successful EVA objectives. This study aims to develop a model of hydration status during EVA using water balance techniques. Methods: Water balance measures were collected on 15 healthy astronauts who performed ≈6-hour simulated microgravity extravehicular activity (EVA) training in the NASA Neutral Buoyancy Laboratory (NBL). Data collected included pre-and post-EVA nude body weight (BW), maximum absorption garment (MAG) weight, Disposable In-suit Drink Bag (DIDB) weight, urine specific gravity (USG), and extra pre-EVA intake (W). Variables were combined to create the water balance model as pre-EVA (Hn)= BWn+ MAGn+ DIDBn+ Wnand post EVA (Hn+1) = BWn+1+ MAGn+1+ DIDBn+1. Urine specific gravity values were used to refine water balance measures into hydration categories: Hydrated, Marginally Hydrated, and Dehydrated. Results: Pre-EVA modeling indicated53% of crew were hydrated, 20% were marginally hydrated, and 27% were dehydrated. Alternately, Hn+1 showed 13% of crew remained hydrated, 47% were marginally hydrated, and 40% were dehydrated at the end of the EVA. Furthermore, 75% of the crewmembers who started sufficiently hydrated finished the run marginally hydrated or dehydrated. According to USG indices presented by Casa and Lawrence, et al. (2000), only 25% of the crew started and remained hydrated throughout the EVA, and those who were dehydrated at the outset stayed dehydrated. Conclusion: Model outcomes assessing hydration status during 6-hour simulated microgravity EVAs demonstrate the necessity to further address hydration requirements for optimal human performance during spaceflight and EVA. This study enables additional baseline development of the Crew State and Risk Model Hydration, Nutrition, and Waste Management component that aims to provide individualized crew state and risk predictions during EVAs. Reference: Casa, D. J., Armstrong, L. E., et al. (2000). National Athletic Trainers’ Association Position Statement: Fluid Replacement for Athletes. Journal of Athletic Training, 35:212-224.

BACKGROUND: Artemis missions will require a new level of crew autonomy around periods of gravitational transition, where sensorimotor disturbances are at their highest. There is a need to define performance thresholds for key sensorimotor assessments that indicate when performance in early extravehicular activities (EVAs) might be impacted or unsafe. This panel presentation will discuss the development of sensorimotor assessments for determining crew preparedness of early EVAs by utilizing a novel portable sensorimotor disorientation analog and other spaceflight analogs. OVERVIEW: To define performance thresholds, a proposed set of sensorimotor assessment tasks must be validated under various spaceflight analogs. A Sensorimotor Disorientation Analog (SDA) was developed that could induce varying levels of disorientation through combined vestibular (galvanic vestibular stimulation (GVS)) and proprioceptive (weighted chest, ankles, and wrists) disruptions. The SDA was first pilot tested using subjective feedback from previously flown astronauts to determine the levels of disorientation that mimic motor performance immediately (R+0) and +24 hours (R+1) postflight. A second study was performed using healthy non-astronaut ground subjects to validate the SDA levels by comparing to astronaut postflight data. The validated SDA was utilized in a third study to map performance in the proposed set of sensorimotor assessment tasks to operational tasks. The assessment tasks were defined based on lessons learned from Apollo and subject matter experts (e.g., flight surgeons) to include the following: 1) aid in progressive adaptation to the novel gravitational environment; 2) provide opportunities to develop strategies to recover from off-nominal body positions; and 3) mimic operational tasks such that crew can self-assess their potential ability to complete their missions. This presentation will conclude with a discussion on future validation studies of the proposed assessment tasks using other spaceflight analogs such as centrifugation and gravity offload systems. DISCUSSION: Exploration class missions will require crew to be able to self-assess and treat their sensorimotor dysfunction after gravity transitions, and in off-nominal situations they may be required to perform provocative, challenging tasks soon after landing. This panel presentation will discuss current and ongoing research strategies to address the sensorimotor risk on safe exploration during Artemis missions.

BACKGROUND: NASA’s objectives for expanding human presence beyond low Earth orbit will require Extravehicular Activities (EVAs) on lunar and planetary surfaces. Given the physiological and functional demands of conducting surface EVAs in a pressurized spacesuit in reduced gravity environments, there is a possibility that crew injury and compromised physiological and/or functional performance may present. OVERVIEW: Many human health and performance knowledge gaps exist in regards to exploration EVA that require characterization to ensure safety, reliability, and mission success. To address knowledge gaps, EVA simulations in Earth-based analog environments and/or spacesuit simulators can be utilized to provide valuable insights into task-based physiologic and metabolic costs, cognitive loads, and associated operational limitations to inform future mission concepts. Physical workloads approaching 60% of maximum metabolic rates and 85% age-predicted heart rate maxima; core body temperatures approaching 100° F; and subjective responses indicating limited spare cognitive capacity via Bedford scale have been observed during ground-based exploration EVA simulations in the NASA Active Response Gravity Offload Simulator (ARGOS) and Neutral Buoyancy Lab (NBL) during simulated planetary EVAs in pressurized suits. Further, ground-based EVA analogs vary in their ability to simulate planetary EVA and resulting physical workloads. DISCUSSION: Metabolic costs, thermal burdens, functional strength, and cognitive impacts have been and must continue to be assessed in ground-based analogs to fully characterize operational demands and crew readiness levels for exploration EVA. Considerations should be given to enabling a new concept of high-tempo surface EVA operations and associated work-rest intervals, understanding human health and performance impacts of evolving commercial suit designs and capabilities, and predictive modeling and decision support capabilities to enable safe and successful EVA operations.

BACKGROUND: For the past 9 years all NASA astronauts received specialized renal ultrasound screening for precursors to renal stones, our so called “mineralized renal material” (MRM), to reduce the possibility of sending a person to space with a renal stone that could cause morbidity and threaten mission objectives. A recent analysis of this data shows no increased incidence of clinical or sub-clinical renal stones associated with spaceflight; thus, our clinical practice guideline has been updated. OVERVIEW: Astronauts previously received a renal ultrasound screening at selection and at every annual recertification exam. In total, 73 individuals have been scanned and 282 total studies have been performed as of April 2023.This data shows no observed statistical change seen in MRM burden pre-to postflight, therefore a reduction in the frequency of the screening exams is appropriate. DISCUSSION: Data presented in this panel have shown no direct correlation between spaceflight and development of MRM or renal stones in astronaut kidneys out to at least 6 months of spaceflight. The MRM burden does not seem to change appreciably over time and so far, has no demonstrated correlation to external factors. Therefore, we find it appropriate, in lieu of yearly exams, to reduce the frequency of screening to: initial selection, first annual exam after selection, and pre/postflight. This balances the screening frequency of our astronauts, against the potential for unnecessary medical procedures, while still serving the purpose of risk reduction.

BACKGROUND: The NASA HRP Evidence Report on the Risk of Renal Stone Formation is being updated based on new information obtained from 9 years of data from NASA’s astronaut renal stone surveillance program. In addition, the Concept of Operations for missions beyond Low Earth Orbit (LEO) was created to supplement the Evidence Report, and the NASA clinical practice guideline(CPG)for renal stone surveillance was updated. OVERVIEW: A literature review was performed to evaluate the state of literature regarding renal stone prevention, mitigation, and management both in terrestrial and spaceflight environments. Current renal stone treatment guidelines for the ISS, which were created by the Inflight Clinical Medicine Working Group and approved by the Multilateral Medical Operations Panel (MMOP)were reviewed, as well as recent ultrasound technology demonstrations onboard the ISS. This information was used in conjunction with emerging evidence from the surveillance program to update the Evidence Report and in-flight Concept of Operations. DISCUSSION: There are known and emerging renal stone prevention strategies including astronaut selection, the use of medications and resistive exercise, early diagnosis with regular urine studies and ultrasound imaging. In-flight treatment options include pharmaceuticals, use of lithotripsy and propulsive ultrasound, placement of percutaneous drains and other modalities. This information is useful to gauge future risks and update our strategies for prevention and management of renal stones in astronauts to reduce the risk of in-flight renal stone colic that could cause morbidity and mission impact.

BACKGROUND: The formation of renal stones in astronauts may pose a considerable threat to crew health and to the completion of mission objectives. Although a history of prior renal stones is an exclusion criterion for initial selection, there have been reported cases of renal stones that have developed after selection. This led to the establishment, nine years ago, of a standardized protocol to screen for the development of renal stones pre-and post-spaceflight in all active astronauts. OVERVIEW: Literature regarding stone makeup, size, location, time to passage, and outcomes were reviewed, as well as incidence of renal stones in astronaut analog populations such as military pilots and the general population. The Lifetime Surveillance of Astronaut Health (LSAH) database was queried and as of 2015 there have been 22 crew members who have reported 36 renal stone events from a population of 357 astronauts, with an incidence of 0.32 events per year. This compares favorably to the incidence of 0.37 to 0.46events per year in commercial pilots. DISCUSSION: The physiologic changes associated with spaceflight have been thought to present an increased risk for the development of stones, including hypercalciuria, decreased urine pH, and reduced urine volume. NASA’s screening program, based on a rigorous ultrasound method, has now provided nine years of clinical data used to reduce the risk of flying an astronaut with a renal stone that could threaten health and mission objectives. This work and data from the ultrasound screening program was used to update the clinical practice guideline for renal stone surveillance and treatment, and other NASA documents and programs that track this risk.

INTRODUCTION Ample evidence exists on the effectiveness of ultrasound in the diagnosis of kidney stones. However, terrestrial practice is mostly concerned with diagnosis of clinically significant urolithiasis. Adapting this non-irradiating, low-cost imaging modality for the asymptomatic astronaut population offers high-sensitivity screening and limits their career radiation dose. METHODS NASA developed a novel ultrasound-based detection and surveillance protocol to identify, categorize, and monitor mineralized renal material (MRM) in astronauts. The term MRM was developed to denote abnormal, presumably calcified, focal material of unknown clinical significance in the kidneys. Sonographic criteria for MRMs include measurable echogenic foci, their detectability in multiple, designated imaging plains, posterior shadowing, and “twinkle” pattern visualized in Color Doppler and/or demonstrated in Spectral Doppler modes. The mere discovery of an MRM does not trigger further imaging or intervention, unless the affected crewmember is mission-assigned, or the MRM meets actionable criteria based on size, location, and sonographic characteristics. If the threshold is met, the crew surgeon is notified, and additional diagnostic imaging and urology consultation are considered. RESULTS In total, 73 individuals have been scanned using our specialized methods, 60 have had more than one study done. As of April 2023, 282 total studies have been performed. So far, over 30 pairs of pre-and postflight studies have been obtained, and the findings are presented elsewhere in this panel. DISCUSSION A surveillance program was initiated nine years ago to screen asymptomatic members of the astronaut corps for renal calcifications, from their initial hiring, through their mission timeframes, and throughout their career. The goal is to reduce the probability that an astronaut will fly with a renal stone that may become symptomatic. This also gives NASA the information it needs to improve screening criteria for future long-duration crewed missions.

Persistent immune system dysregulation has been documented to occur in astronauts participating in orbital spaceflight onboard the International Space Station. The phenomenon consists of reductions in T and NK cell function, altered cytokine profiles, persistent inflammation, and the subclinical reactivation of latent herpesviruses. In select crewmembers the dysregulation does actually lead to clinical symptoms, primarily atypical allergy or atopic dermatitis/zoster. Flow cytometry has served a central role defining the ‘immune assessment’ panel of assays that allow monitoring of astronauts. The cytometry assays which have been utilized include: 1. Peripheral leukocyte subsets 2. T cell function 3. Monocyte function 4. NK cell function 5. Intracellular cytokine analysis 6. Virus-specific T cell number (tetramer assay) 7. Virus-specific T cell function (peptide stimulation) 8. Leukocyte-bacterial challenge cytometry 9. Cytometric bead/multiplex array (soluble proteins) The use of these assays has been validated through various ISS flight investigations to define, to varying degrees, both in-flight, and post-flight immune system alterations. The kinetics of the dysregulation through the various phases of spaceflight, as well as post-flight recovery, have also been documented. To allow the science to occur within the orbital constraints of a spaceflight investigation, particular sample collection and processing techniques were developed compatible with the delays associated with terrestrial processing of in-flight samples. A subset of the assays has been adapted to routine monitoring of astronauts via a NASA ‘ISS Standard Measures’ activity, with the data from a specific crew then provided to all science investigators for that particular mission. This battery of cytometry assays has also been applied, through ground investigations, to several terrestrial ‘spaceflight analog’ populations. The purpose was to validate the analog which most closely replicates the in-flight observed pattern of alterations, generally believed to be winterover at an Antarctica station. To assist in determination of clinical risk, the assay panel has also been applied to investigations of various terrestrial patient populations, particularly zoster patients. As NASA is initiating crewed lunar missions via the ‘Artemis’ program, deployment of a miniaturized, microgravity-compatible flow cytometer, would be extremely beneficial to allow real time monitoring of crewmembers. Real time medical data could influence use of several countermeasures options during deep space missions. Several such instruments have been developed and validated to varying degrees of success. Assay details and summary findings across the various flight and ground platforms will be presented, as will current status in developing such technology for in-flight use.

Welcome to the April 2024 issue of the Lifetime Surveillance of Astronaut Health (LSAH) Newsletter. In this issue, we celebrate LSAH lead, Dr. Mary Wear’s retirement, inform you of the Apollo Records Synthesis Project (ARSP), and recap information shared at the 2024 Human Research Program (HRP) Investigators’ Workshop (IWS) by our LSAH Epidemiologists and NASA HRP team.

An aspiration for EIMO datascope is to realize artificial intelligence-enhanced solutions for analysis of crew health & performance data and to facilitate clinical decision support for autonomous medical operations. A vision proposed to the meeting participants was that of a “system of systems,” whereby EIMO will utilize AI-supported natural language processing and machine learning techniques to synthesize embedded reference databases and real-time data streams [input vectors] from multiple data sources to continuously and seamlessly assess crew health & performance. Constituent input vectors may include environmental controls, countermeasures data, behavioral data, physiologic wearables, point-of-care laboratory tests, personalized medical records, inventory trade space risk assessments, COTS medical databases, and ground support inputs. An ideal AI capability would possess trained fusion algorithms to cross reference input vectors with medical ‘knowledge’ [cultivated database] to stratify relevant data streams for predictive and actionable capabilities. In addition, EIMO will ideally have a degree of mobility, in that it can be accessed and can push/pull data within and between multiple vehicles/habitats.