Radiotheranostics in oncology: Making precision medicine possible.

A quintessential setting for precision medicine, theranostics refers to a rapidly evolving field of medicine in which disease is diagnosed followed by treatment of disease-positive patients using tools for the therapy identical or similar to those used for the diagnosis. Against the backdrop of only-treat-when-visualized, the goal is a high therapeutic index with efficacy markedly surpassing toxicity. Oncology leads the way in theranostics innovation, where the approach has become possible with the identification of unique proteins and other factors selectively expressed in cancer versus healthy tissue, advances in imaging technology able to report these tissue factors, and major understanding of targeting chemicals and nanodevices together with methods to attach labels or warheads for imaging and therapy. Radiotheranostics-using radiopharmaceuticals-is becoming routine in patients with prostate cancer and neuroendocrine tumors who express the proteins PSMA (prostate-specific membrane antigen) and SSTR2 (somatostatin receptor 2), respectively, on their cancer. The palpable excitement in the field stems from the finding that a proportion of patients with large metastatic burden show complete and partial responses, and this outcome is catalyzing the search for more radiotheranostics approaches. Not every patient will benefit from radiotheranostics; but, for those who cross the target-detected line, the likelihood of response is very high.

Recommendations for accelerating open preprint peer review to improve the culture of science.

Peer review is an important part of the scientific process, but traditional peer review at journals is coming under increased scrutiny for its inefficiency and lack of transparency. As preprints become more widely used and accepted, they raise the possibility of rethinking the peer-review process. Preprints are enabling new forms of peer review that have the potential to be more thorough, inclusive, and collegial than traditional journal peer review, and to thus fundamentally shift the culture of peer review toward constructive collaboration. In this Consensus View, we make a call to action to stakeholders in the community to accelerate the growing momentum of preprint sharing and provide recommendations to empower researchers to provide open and constructive peer review for preprints.

LC3B labeling of the parasitophorous vacuole membrane of Plasmodium berghei liver stage parasites depends on the V-ATPase and ATG16L1.

The protozoan parasite Plasmodium, the causative agent of malaria, undergoes an obligatory stage of intra-hepatic development before initiating a blood-stage infection. Productive invasion of hepatocytes involves the formation of a parasitophorous vacuole (PV) generated by the invagination of the host cell plasma membrane. Surrounded by the PV membrane (PVM), the parasite undergoes extensive replication. During intracellular development in the hepatocyte, the parasites provoke the Plasmodium-associated autophagy-related (PAAR) response. This is characterized by a long-lasting association of the autophagy marker protein, and ATG8 family member, LC3B with the PVM. LC3B localization at the PVM does not follow the canonical autophagy pathway since upstream events specific to canonical autophagy are dispensable. Here, we describe that LC3B localization at the PVM of Plasmodium parasites requires the V-ATPase and its interaction with ATG16L1. The WD40 domain of ATG16L1 is crucial for its recruitment to the PVM. Thus, we provide new mechanistic insight into the previously described PAAR response targeting Plasmodium liver stage parasites.

Neuromodulatory effects of parietal high-definition transcranial direct-current stimulation on network-level activity serving fluid intelligence.

Fluid intelligence (Gf) involves rational thinking skills and requires the integration of information from different cortical regions to resolve novel complex problems. The effects of non-invasive brain stimulation on Gf have been studied in attempts to improve Gf, but such studies are rare and the few existing have reached conflicting conclusions. The parieto-frontal integration theory of intelligence (P-FIT) postulates that the parietal and frontal lobes play a critical role in Gf. To investigate the suggested role of parietal cortices, we applied high-definition transcranial direct current stimulation (HD-tDCS) to the left and right parietal cortices of 39 healthy adults (age 19-33 years) for 20 min in three separate sessions (left active, right active and sham). After completing the stimulation session, the participants completed a logical reasoning task based on Raven's Progressive Matrices during magnetoencephalography. Significant neural responses at the sensor level across all stimulation conditions were imaged using a beamformer. Whole-brain, spectrally constrained functional connectivity was then computed to examine the network-level activity. Behaviourally, we found that participants were significantly more accurate following left compared to right parietal stimulation. Regarding neural findings, we found significant HD-tDCS montage-related effects in brain networks thought to be critical for P-FIT, including parieto-occipital, fronto-occipital, fronto-parietal and occipito-cerebellar connectivity during task performance. In conclusion, our findings showed that left parietal stimulation improved abstract reasoning abilities relative to right parietal stimulation and support both P-FIT and the neural efficiency hypothesis. KEY POINTS: Abstract reasoning is a critical component of fluid intelligence and is known to be served by multispectral oscillatory activity in the fronto-parietal cortices. Recent studies have aimed to improve abstract reasoning abilities and fluid intelligence overall through behavioural training, but the results have been mixed. High-definition transcranial direct-current stimulation (HD-tDCS) applied to the parietal cortices modulated task performance and neural oscillations during abstract reasoning. Left parietal stimulation resulted in increased accuracy and decreased functional connectivity between occipital regions and frontal, parietal, and cerebellar regions. Future studies should investigate whether HD-tDCS alters abstract reasoning abilities in those who exhibit declines in performance, such as healthy ageing populations.

Circulating T Cells Are Not Sufficient for Protective Immunity against Virulent Francisella tularensis.

Pulmonary infections elicit a combination of tissue-resident and circulating T cell responses. Understanding the contribution of these anatomically distinct cellular pools in protective immune responses is critical for vaccine development. Francisella tularensis is a highly virulent bacterium capable of causing lethal systemic disease following pulmonary infection for which there is no currently licensed vaccine. Although T cells are required for survival of F. tularensis infection, the relative contribution of tissue-resident and circulating T cells is not completely understood, hampering design of effective, long-lasting vaccines directed against this bacterium. We have previously shown that resident T cells were not sufficient to protect against F. tularensis, suggesting circulating cells may serve a critical role in host defense. To elucidate the role of circulating T cells, we used a model of vaccination and challenge of parabiotic mice. Intranasally infected naive mice conjoined to immune animals had increased numbers of circulating memory T cells and similar splenic bacterial burdens as vaccinated-vaccinated pairs. However, bacterial loads in the lungs of naive parabionts were significantly greater than those observed in vaccinated-vaccinated pairs, but despite early control of F. tularensis replication, all naive-vaccinated pairs succumbed to infection. Together, these data define the specific roles of circulating and resident T cells in defense against infection that is initiated in the pulmonary compartment but ultimately causes disseminated disease. These data also provide evidence for employing vaccination strategies that elicit both pools of T cells for immunity against F. tularensis and may be a common theme for other disseminating bacterial infections.

Contribution of Lipid Mediators in Divergent Outcomes following Acute Bacterial and Viral Lung Infections in the Obese Host.

Obesity is considered an important comorbidity for a range of noninfectious and infectious disease states including those that originate in the lung, yet the mechanisms that contribute to this susceptibility are not well defined. In this study, we used the diet-induced obesity (DIO) mouse model and two models of acute pulmonary infection, Francisella tularensis subspecies tularensis strain SchuS4 and SARS-CoV-2, to uncover the contribution of obesity in bacterial and viral disease. Whereas DIO mice were more resistant to infection with SchuS4, DIO animals were more susceptible to SARS-CoV-2 infection compared with regular weight mice. In both models, neither survival nor morbidity correlated with differences in pathogen load, overall cellularity, or influx of inflammatory cells in target organs of DIO and regular weight animals. Increased susceptibility was also not associated with exacerbated production of cytokines and chemokines in either model. Rather, we observed pathogen-specific dysregulation of the host lipidome that was associated with vulnerability to infection. Inhibition of specific pathways required for generation of lipid mediators reversed resistance to both bacterial and viral infection. Taken together, our data demonstrate disparity among obese individuals for control of lethal bacterial and viral infection and suggest that dysregulation of the host lipidome contributes to increased susceptibility to viral infection in the obese host.

Differences in Tic Severity Among Adolescent Girls and Boys with Tourette Syndrome During the Pandemic.

Limited data are available regarding the impact of the coronavirus disease 2019 (COVID-19) pandemic on adolescents with Tourette syndrome (TS). We sought to compare sex differences in tic severity experienced by adolescents before and during the COVID-19 pandemic. We extracted from the electronic health record and retrospectively reviewed Yale Global Tic Severity Scores (YGTSS) from adolescents (ages 13 through 17) with TS presenting to our clinic before (36 months) and during (24 months) the pandemic. A total of 373 unique adolescent patient encounters (prepandemic: 199; pandemic: 173) were identified. Compared with prepandemic, girls accounted for a significantly greater proportion of visits during the pandemic (p < 0.001). Prepandemic, tic severity did not differ between girls and boys. During the pandemic, compared with girls, boys had less clinically severe tics (p = 0.003). During the pandemic, older girls, but not boys, had less clinically severe tics (ρ =- 0.32, p = 0.003). These findings provide evidence that, regarding tic severity assessed with YGTSS, the experiences of adolescent girls and boys with TS have differed during the pandemic.

Diagnostic journey and life impact of cholangiocarcinoma: results from surveys of patient and caregiver experiences.

Aim: To understand cholangiocarcinoma symptoms, diagnosis and treatment experience from the patient and caregiver perspective, including cholangiocarcinoma's impact on daily life, quality of life (QoL) and mental health. Methods: Patients and caregivers participated in two online surveys (in partnership with the Cholangiocarcinoma Foundation). Results: The patient survey data (n = 707) show a substantial impact of cholangiocarcinoma on QoL and mental health, with 34% of patients reporting symptoms consistent with moderately severe/severe depression. The caregiver survey data (n = 60) show that although caregivers experience satisfaction in their role of caring for a loved one, managing the demands of caregiving exacts a physical, mental and emotional toll. Conclusion: These surveys highlight the need for better palliative and supportive care interventions.

What is this article about? It shows results from two surveys, one for people with cholangiocarcinoma (CCA, pronounced ko·lan·jee·o·car·sin·no·muh), and one for caregivers (people who take care of family or friends with CCA without payment). CCA is a rare and aggressive cancer. The caregivers we surveyed were not necessarily taking care of the people with CCA who we surveyed. We did the surveys to find out how CCA changed the lives of people in these two groups. What were the results? We surveyed 707 people with CCA. Patients reported in the survey that having CCA impacted their daily lives in lots of ways. Most needed help with daily chores like housekeeping and shopping. Both tiredness and anxiety were reported by about two in three people with CCA. More than one in three had said they had symptoms indicating potential depression, which means patients should have their mental health evaluated. CCA also reduced their sexual desire and intimacy with their partner. We surveyed 60 caregivers who reported both good and bad experiences taking care of a person with CCA. The good experiences included knowing that their loved one was well cared for and learning to deal with difficult situations. Many caregivers also felt closer to their loved one with CCA. The bad experiences included exhaustion and emotional and mental stress. Caregivers felt challenged by trying to understand CCA and the treatment options available. What do the results of the study mean? Patients with CCA and their caregivers need more help and support.

Parkin and PINK1 mitigate STING-induced inflammation.

Although serum from patients with Parkinson's disease contains elevated levels of numerous pro-inflammatory cytokines including IL-6, TNF, IL-1ß, and IFNγ, whether inflammation contributes to or is a consequence of neuronal loss remains unknown1. Mutations in parkin, an E3 ubiquitin ligase, and PINK1, a ubiquitin kinase, cause early onset Parkinson's disease2,3. Both PINK1 and parkin function within the same biochemical pathway and remove damaged mitochondria from cells in culture and in animal models via mitophagy, a selective form of autophagy4. The in vivo role of mitophagy, however, is unclear, partly because mice that lack either PINK1 or parkin have no substantial Parkinson's-disease-relevant phenotypes5-7. Mitochondrial stress can lead to the release of damage-associated molecular patterns (DAMPs) that can activate innate immunity8-12, suggesting that mitophagy may mitigate inflammation. Here we report a strong inflammatory phenotype in both Prkn-/- and Pink1-/- mice following exhaustive exercise and in Prkn-/-;mutator mice, which accumulate mutations in mitochondrial DNA (mtDNA)13,14. Inflammation resulting from either exhaustive exercise or mtDNA mutation is completely rescued by concurrent loss of STING, a central regulator of the type I interferon response to cytosolic DNA15,16. The loss of dopaminergic neurons from the substantia nigra pars compacta and the motor defect observed in aged Prkn-/-;mutator mice are also rescued by loss of STING, suggesting that inflammation facilitates this phenotype. Humans with mono- and biallelic PRKN mutations also display elevated cytokines. These results support a role for PINK1- and parkin-mediated mitophagy in restraining innate immunity.

Pituitary hypophysitis in granulomatosis with polyangiitis (GPA): a case series.

Granulomatosis with polyangiitis (GPA) rarely involves the pituitary gland. Pituitary involvement has been reported in ~ 1% of all cases of GPA. Most commonly, pituitary swelling and inflammation results in symptoms due to pituitary mass effect and arginine vasopressin deficiency. To date, there are no pituitary-specific treatment guidelines for this rare condition. We present three patients with GPA-related hypophysitis highlighting the spectrum of pituitary involvement. All three patients were successfully treated with immunosuppressive regimens that included rituximab (RTX). Following remission induction with high-dose glucocorticoids, patients received 6 monthly RTX for remission maintenance. RTX was well tolerated without significant side effects.

Locked and loaded: correlates of in-home firearm storage beliefs and behaviours.

OBJECTIVES: To understand how crime and victimisation fears and risks operate alongside social status threats and motivations to shape unsafe in-home firearm storage practices and beliefs. METHODS: Using data from firearm owners identified in a nationwide sample surveyed in 2023, this study examined how in-home loaded firearm accessibility, firearm storage practice and firearm safety beliefs are associated with: fear of crime and victimisation; perceived and personal victimisation; racial resentment; cultural and status threats; and masculinity threats. Regression models also accounted for the role of gender, race, marital status, political affiliation, geographic region and protective motivation for firearm ownership. RESULTS: Over 40% of firearm owners reported having a loaded firearm 'always accessible' at home, and almost half think homes with firearms are safer than those without. About one-third of owners reported storing firearms locked but still loaded. Crime and victimisation fears and threats were unrelated to firearm storage behaviours and beliefs; however, firearm owners who experience higher levels of sociocultural anxiety are more likely to always have a loaded firearm accessible at home, store firearms locked and loaded, and believe that firearms make homes safer. CONCLUSIONS: Identifying the barriers to safer storage beliefs and behaviours is essential for refining and enhancing effective firearm injury prevention strategies. Sociocultural anxieties may not reflect concrete threats to physical safety, but they can be experienced as feelings of insecurity, instability and distress that-for some Americans-may be managed by knowing they have a (loaded) firearm within reach.

Decidual cast: a rare cause of genital tract obstruction.

Decidual cast is a little-known entity characterized by sloughing of the endometrium in several large pieces or in one cylindrical or membranous piece retaining the shape of the uterine cavity. Accounts of the diagnosis are sporadic and have not previously appeared in the pediatric imaging literature. We describe a case of a post-menarchal adolescent girl presenting with abnormal uterine bleeding, severe dysmenorrhea, and imaging features of genital tract obstruction, the cause of which was found to be a large decidual cast during examination under anesthesia. While rare, awareness of this phenomenon should be useful to pediatric imagers as the combination of bleeding and obstructive symptoms produces a confusing picture that may lead to a protracted clinical and imaging course.

Former dementia caregivers' high and low point narratives: what is remembered, and how is it shared?

OBJECTIVES: To characterize core themes conveyed by caregivers when sharing narratives of high and low caregiving points and to describe how caregivers structured these narratives. METHODS: Using consensual qualitative research and thematic analysis, high and low point narratives from 32 former caregivers of persons living with dementia were examined. RESULTS: High point narrative themes involved strengthening relationships with care partners, fulfillment derived from care, lighthearted moments, and fostering the care partners' joy and dignity. Low point narratives involved family conflict and lack of support, personal deficiencies, loss of the caregivers' 'pre-caregiving' life, health system failures, and alienation from their care partner. Across high and low points, caregivers' narratives were structured by three types of narrative elaborations; details unnecessary for factual recall but which enriched narrative sharing. CONCLUSION: Themes across high and low point narratives encompassed relational issues, how caregiving shaped the caregiver's self-efficacy, and factors that made navigating caregiving easier or more difficult. Both high point and low point narration often involved describing positive aspects of caregiving (PAC). Narrative elaborations may be used by former caregivers to engage in deeper evaluation of their caregiving experiences. We consider how psychotherapeutic techniques can help former caregivers reframe maladaptive narratives, supporting their mental health.

Dementia Caregiving Experiences Among Korean Americans: Qualitative Inquiry Using the Stress Process Perspective.

Dementia caregiving involves a challenging and complex process, especially for immigrant families. Using a qualitative method, this study provides an in-depth exploration of caregiving experiences among Korean American caregivers of people living with dementia. Based on various sampling strategies, 16 Korean American caregivers of family members/relatives with dementia were recruited in the greater Los Angeles area. Guided by the stress process model and the constant comparative method, themes and subthemes were derived and categorized into four domains: (1) background/context; (2) perception/appraisal; (3) resources/coping, and (4) caregiver burden/reward. Findings suggest that intervention efforts should focus on educating and training dementia caregivers.

Disturbances in primary visual processing as a function of healthy aging.

For decades, visual entrainment paradigms have been widely used to investigate basic visual processing in healthy individuals and those with neurological disorders. While healthy aging is known to be associated with alterations in visual processing, whether this extends to visual entrainment responses and the precise cortical regions involved is not fully understood. Such knowledge is imperative given the recent surge in interest surrounding the use of flicker stimulation and entrainment in the context of identifying and treating Alzheimer's disease (AD). In the current study, we examined visual entrainment in eighty healthy aging adults using magnetoencephalography (MEG) and a 15 Hz entrainment paradigm, while controlling for age-related cortical thinning. MEG data were imaged using a time-frequency resolved beamformer and peak voxel time series were extracted to quantify the oscillatory dynamics underlying the processing of the visual flicker stimuli. We found that, as age increased, the mean amplitude of entrainment responses decreased and the latency of these responses increased. However, there was no effect of age on the trial-to-trial consistency in phase (i.e., inter-trial phase locking) nor amplitude (i.e., coefficient of variation) of these visual responses. Importantly, we discovered that the relationship between age and response amplitude was fully mediated by the latency of visual processing. These results indicate that aging is associated with robust changes in the latency and amplitude of visual entrainment responses within regions surrounding the calcarine fissure, which should be considered in studies examining neurological disorders such as AD and other conditions associated with increased age.

Protective Geometry and Reproductive Anatomy as Candidate Determinants of Clutch Size Variation in Pentatomid Bugs.

AbstractMany animals lay their eggs in clusters. Eggs on the periphery of clusters can be at higher risk of mortality. We asked whether the most commonly occurring clutch sizes in pentatomid bugs could result from geometrical arrangements that maximize the proportion of eggs in the cluster's interior. Although the most common clutch sizes do not correspond with geometric optimality, stink bugs do tend to lay clusters of eggs in shapes that protect increasing proportions of their offspring as clutch sizes increase. We also considered whether ovariole number, an aspect of reproductive anatomy that may be a fixed trait across many pentatomids, could explain observed distributions of clutch sizes. The most common clutch sizes across many species correspond with multiples of ovariole number. However, there are species with the same number of ovarioles that lay clutches of widely varying size, among which multiples of ovariole number are not overrepresented. In pentatomid bugs, reproductive anatomy appears to be more important than egg mass geometry in determining clutch size uniformity. In addition, our analysis demonstrates that groups of animals with little variation in ovariole number may nonetheless lay a broad range of clutch shapes and sizes.

Feasibility of [18F]fluoropivalate hybrid PET/MRI for imaging lower and higher grade glioma: a prospective first-in-patient pilot study.

PURPOSE: MRI and PET are used in neuro-oncology for the detection and characterisation of lesions for malignancy to target surgical biopsy and to plan surgical resections or stereotactic radiosurgery. The critical role of short-chain fatty acids (SCFAs) in brain tumour biology has come to the forefront. The non-metabolised SCFA radiotracer, [18F]fluoropivalate (FPIA), shows low background signal in most tissues except eliminating organs and has appropriate human dosimetry. Tumour uptake of the radiotracer is, however, unknown. We investigated the uptake characteristics of FPIA in this pilot PET/MRI study. METHODS: Ten adult glioma subjects were identified based on radiological features using standard-of-care MRI prior to any surgical intervention, with subsequent histopathological confirmation of glioma subtype and grade (lower-grade - LGG - and higher-grade - HGG - patients). FPIA was injected as an intravenous bolus injection (range 342-368 MBq), and dynamic PET and MRI data were acquired simultaneously over 66 min. RESULTS: All patients tolerated the PET/MRI protocol. Three patients were reclassified following resection and histology. Tumour maximum standardised uptake value (SUVmax,60) increased in the order LGG (WHO grade 2) < HGG (WHO grade 3) < HGG (WHO grade 4). The net irreversible solute transfer, Ki, and influx rate constant, K1, were significantly higher in HGG (p < 0.05). Of the MRI variables studied, DCE-MRI-derived extravascular-and-extracellular volume fraction (ve) was high in tumours of WHO grade 4 compared with other grades (p < 0.05). SLC25A20 protein expression was higher in HGG compared with LGG. CONCLUSION: Tumoural FPIA PET uptake is higher in HGG compared to LGG. This study supports further investigation of FPIA PET/MRI for brain tumour imaging in a larger patient population. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov, NCT04097535.

Partial refuges from biological control due to intraspecific variation in protective host traits.

Predicting how much of a host or prey population may be attacked by their natural enemies is fundamental to several subfields of applied ecology, particularly biological control of pest organisms. Hosts or prey can occupy refuges that prevent them from being killed by natural enemies, but habitat or ecological refuges are challenging or impossible to predict in a laboratory setting-which is often where efficacy and specificity testing of candidate biological control agents is done. Here we explore how intraspecific variation in continuous traits of individuals or groups that confer some protection from natural enemy attack-even after the natural enemy has encountered the prey-could provide partial refuges. The size of these trait-based refuges (i.e., the proportion of prey that survive natural enemy encounters due to protective traits) should depend on the relationship between trait values and host/prey susceptibility to natural enemy attack and on how common different trait values are within a host/prey population. These can be readily estimated in laboratory testing of natural enemy impact on target or nontarget prey or hosts as long as sufficient host material is available. We provide a general framework for how intraspecific variation in protective host traits could be integrated into biological control research, specifically with reference to nontarget testing as part of classical biological control programs. As a case study, we exposed different host clutch sizes of target (pest) and nontarget (native species) stink bug (Hemiptera: Pentatomidae) species to a well-studied exotic biocontrol agent, the egg parasitoid Trissolcus japonicus (Hymenoptera: Scelionidae). We predicted that the smallest and largest clutches would occupy trait-based refuges from parasitism. Although we observed several behavioral and reproductive responses to variation in host egg mass size by T. japonicus, they did not translate to increases in host survival large enough to change the conclusions of nontarget testing. We encourage researchers to investigate intraspecific variation in a wider variety of protective host and prey traits and their consequences for refuge size.

Cutting Edge: Lung-Resident T Cells Elicited by SARS-CoV-2 Do Not Mediate Protection against Secondary Infection.

Immunity to pulmonary infection typically requires elicitation of lung-resident T cells that subsequently confer protection against secondary infection. The presence of tissue-resident T cells in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) convalescent patients is unknown. Using a sublethal mouse model of coronavirus disease 2019, we determined if SARS-CoV-2 infection potentiated Ag-specific pulmonary resident CD4+ and CD8+ T cell responses and if these cells mediated protection against secondary infection. S protein-specific T cells were present in resident and circulating populations. However, M and N protein-specific T cells were detected only in the resident T cell pool. Using an adoptive transfer strategy, we found that T cells from SARS-CoV-2 immune animals did not protect naive mice. These data indicate that resident T cells are elicited by SARS-CoV-2 infection but are not sufficient for protective immunity.

Online Intervention for Caregivers of Children with Early Traumatic Brain Injury: Pilot Trial.

OBJECTIVE: To assess the feasibility and acceptability of an online parenting-skills program for caregivers of young children with traumatic brain injury (TBI). Positive parenting contributes to recovery following early TBI and social and emotional development in typically developing children. Yet, few interventions have been designed to support psychosocial recovery and subsequent development after early TBI. METHODS: This study protocol was registered with clinicaltrials.gov (NCT05160194). We utilized an academic hospital's Trauma Registry to recruit caregivers of children, ages 0-4 years, previously hospitalized for TBI. The GROW intervention integrated six online learning modules with videoconference meetings with a coach to review and practice skills while receiving in vivo coaching and feedback. Interactive modules addressed strategies for responsive parenting, stimulating cognition, and managing parenting stress. Enrollment and retention rates served as feasibility metrics and satisfaction surveys assessed acceptability. RESULTS: 18 of 72 families contacted (25%) consented, and 11 of 18 (61%) completed the intervention and follow-up assessments. All participants rated the intervention as helpful and indicated that they would recommend the intervention to others. All endorsed a better understanding of brain injury and how to optimize their child's recovery and development. Both coaches rated intervention delivery as comparable to traditional face-to-face treatment. CONCLUSIONS: Low levels of uptake and initial engagement underscore the challenges of intervening with caregivers following early TBI, which likely were exacerbated due to the COVID-19 pandemic. High levels of acceptability and perceived benefit support the potential utility of GROW while highlighting the need to improve accessibility and early engagement.