Evidence of compensatory neural hyperactivity in a subgroup of chemotherapy-treated breast cancer survivors and its association with brain aging.

Chemotherapy-related cognitive impairment (CRCI) remains poorly understood in terms of the mechanisms of cognitive decline. Neural hyperactivity has been reported on average in cancer survivors, but it is unclear which patients demonstrate this neurophenotype, limiting precision medicine in this population. We evaluated a retrospective sample of 80 breast cancer survivors and 80 non-cancer controls, age 35-73, for which we had previously identified and validated three data-driven, biological subgroups (biotypes) of CRCI. We measured neural activity using the z-normalized percent amplitude of fluctuation from resting state functional magnetic resonance imaging (MRI). We tested established, quantitative criteria to determine if hyperactivity can accurately be considered compensatory. We also calculated brain age gap by applying a previously validated algorithm to anatomic MRI. We found that neural activity differed across the three CRCI biotypes and controls (F = 13.5, p < 0.001), with Biotype 2 demonstrating significant hyperactivity compared to the other groups (p < 0.004, corrected), primarily in prefrontal regions. Alternatively, Biotypes 1 and 3 demonstrated significant hypoactivity (p < 0.02, corrected). Hyperactivity in Biotype 2 met several of the criteria to be considered compensatory. However, we also found a positive relationship between neural activity and brain age gap in these patients (r = 0.45, p = 0.042). Our results indicated that neural hyperactivity is specific to a subgroup of breast cancer survivors and, while it seems to support preserved cognitive function, it could also increase the risk of accelerated brain aging. These findings could inform future neuromodulatory interventions with respect to the risks and benefits of up or downregulation of neural activity.

Strength of spatial correlation between gray matter connectivity and patterns of proto-oncogene and neural network construction gene expression is associated with diffuse glioma survival.

Introduction: Like other forms of neuropathology, gliomas appear to spread along neural pathways. Accordingly, our group and others have previously shown that brain network connectivity is highly predictive of glioma survival. In this study, we aimed to examine the molecular mechanisms of this relationship via imaging transcriptomics. Methods: We retrospectively obtained presurgical, T1-weighted MRI datasets from 669 adult patients, newly diagnosed with diffuse glioma. We measured brain connectivity using gray matter networks and coregistered these data with a transcriptomic brain atlas to determine the spatial co-localization between brain connectivity and expression patterns for 14 proto-oncogenes and 3 neural network construction genes. Results: We found that all 17 genes were significantly co-localized with brain connectivity (p < 0.03, corrected). The strength of co-localization was highly predictive of overall survival in a cross-validated Cox Proportional Hazards model (mean area under the curve, AUC = 0.68 +/- 0.01) and significantly (p < 0.001) more so for a random forest survival model (mean AUC = 0.97 +/- 0.06). Bayesian network analysis demonstrated direct and indirect causal relationships among gene-brain co-localizations and survival. Gene ontology analysis showed that metabolic processes were overexpressed when spatial co-localization between brain connectivity and gene transcription was highest (p < 0.001). Drug-gene interaction analysis identified 84 potential candidate therapies based on our findings. Discussion: Our findings provide novel insights regarding how gene-brain connectivity interactions may affect glioma survival.

Pilot trial testing the effects of exercise on chemotherapy-induced peripheral neurotoxicity (CIPN) and the interoceptive brain system.

Purpose: Chemotherapy-induced peripheral neurotoxicity (CIPN) is a prevalent, dose-limiting, tough-to-treat toxicity involving numbness, tingling, and pain in the extremities with enigmatic pathophysiology. This randomized controlled pilot study explored the feasibility and preliminary efficacy of exercise during chemotherapy on CIPN and the role of the interoceptive brain system, which processes bodily sensations. Methods: Nineteen patients (65±11 years old, 52% women; cancer type: breast, gastrointestinal, multiple myeloma) starting neurotoxic chemotherapy were randomized to 12 weeks of exercise (home-based, individually tailored, moderate intensity, progressive walking and resistance training) or active control (nutrition education). At pre-, mid-, and post-intervention, we assessed CIPN symptoms (primary clinical outcome: CIPN-20), CIPN signs (tactile sensitivity using monofilaments), and physical function (leg strength). At pre- and post-intervention, we used task-free ("resting") fMRI to assess functional connectivity in the interoceptive brain system, involving the salience and default mode networks. Results: The study was feasible (74-89% complete data across measures) and acceptable (95% retention). We observed moderate/large beneficial effects of exercise on CIPN symptoms (CIPN-20, 0-100 scale: -7.9±5.7, effect size [ES]=-0.9 at mid-intervention; -4.8±7.3, -ES=0.5 at post-intervention), CIPN signs (ES=-1.0 and -0.1), and physical function (ES=0.4 and 0.3). Patients with worse CIPN after neurotoxic chemotherapy had lower functional connectivity within the default mode network (R2=40-60%) and higher functional connectivity within the salience network (R2=20-40%). Exercise tended to increase hypoconnectivity and decrease hyperconnectivity seen in CIPN (R2 = 12%). Conclusion: Exercise during neurotoxic chemotherapy is feasible and may attenuate CIPN symptoms and signs, perhaps via changes in interoceptive brain circuitry. Future work should test for replication with larger samples. ClinicalTrials.gov identifier NCT03021174.

An Exploratory Analysis of Contributors to Cognitive Functioning Among Sexual and Gender Minority Individuals Who Had COVID-19.

Sexual and gender minority (SGM) individuals face mental health disparities. However, research analyzing SGM people's mental health after a COVID-19 diagnosis is scarce. In this secondary analysis of a remote study, we 1) examined associations between cognitive and psychosocial health and 2) explored differences between these health outcomes among SGM (n = 14) and heterosexual cisgender (n = 64) U.S. adults who had COVID-19. We used the Patient Reported Outcome Measures Information System (PROMIS) v2.0 to assess subjective cognition and the BrainCheck cognitive test to analyze objective cognition. We administered the Perceived Stress Scale and PROMIS 57 Profile V.2.0 to measure psychosocial health. SGM COVID-19 survivors had worse scores in depression, anxiety, sleep disturbance, pain, stress, and objective cognition than heterosexual cisgender participants (p-values < .05). Objective cognition was associated with age, SGM classification, racial or ethnic minority classification, income, comorbidities, COVID-19 severity, number of symptoms, and pain (|0.137| < r < |0.373|, p-values < .05). Subjective cognition was associated with comorbidities, number of symptoms, depression, anxiety, sleep disturbance, pain, and stress (|0.158| < r < |0.537|, p-values < .05). Additional studies are needed to expand what is known about post-COVID-19 health disparities and to guide policies and interventions that promote cognitive functioning.

Driving among individuals with chronic conditions: A systematic review of applied research using kinematic driving sensors.

BACKGROUND: Kinematic driving data studies are a novel methodology relevant to health care, but prior studies have considerable variance in their methods, populations, and findings suggesting a need for critical analysis and appraisal for feasibility and methodological guidelines. METHODS: We assessed kinematic driving studies of adults with chronic conditions for study feasibility, characteristics, and key findings, to generate recommendations for future study designs, and to identify promising directions for applications of kinematic driving data. PRISMA was used to guide the review and searches included PubMed, CINAHL, and Compendex. Of 379 abstract/titles screened, 49 full-text articles were reviewed, and 29 articles met inclusion criteria of analyzing trip-level kinematic driving data from adult drivers with chronic conditions. RESULTS: The predominant chronic conditions studied were Alzheimer's disease and related Dementias, obstructive sleep apnea, and diabetes mellitus. Study objectives included feasibility testing of kinematic driving data collection in the context of chronic conditions, comparisons of simulation with real-world kinematic driving behavior, assessments of driving behavior effects associated with chronic conditions, and prognostication or disease classification drawn from kinematic driving data. Across the studies, there was no consensus on devices, measures, or sampling parameters; however, studies showed evidence that driving behavior could reliably differentiate between adults with chronic conditions and healthy controls. CONCLUSIONS: Vehicle sensors can provide driver-specific measures relevant to clinical assessment and interventions. Using kinematic driving data to assess and address driving measures of individuals with multiple chronic conditions is positioned to amplify a functional outcome measure that matters to patients.

Preliminary evaluation of novel Bodily Attention Task to assess the role of the brain in chemotherapy-induced peripheral neurotoxicity (CIPN).

Chemotherapy-induced peripheral neurotoxicity (CIPN) is a common, sometimes dose-limiting side effect of neurotoxic chemotherapy. Treatment is limited because its pathophysiology is poorly understood. Compared to research on peripheral mechanisms, the role of the brain in CIPN is understudied and it may be important to develop better treatments. We propose a novel task that assesses brain activation associated with attention to bodily sensations (interoception), without the use of painful stimulation, to understand how CIPN symptoms may be processed in the brain. The goals of this preliminary study were to assess, 1) feasibility of the task, 2) sensitivity to changes in brain activity, and 3) suitability for assessing relationships between brain activation and CIPN severity. Eleven participants with varying types of cancer completed a brain fMRI scan and rated CIPN severity (CIPN-20) before and/or 12 weeks after starting neurotoxic chemotherapy. The Bodily Attention Task is a 7.5-min long fMRI task involving attentional focus on the left fingertips, the heart, or a flashing word "target" for visual attention (reference condition). Feasibility was confirmed, as 73% of all data collected were usable and participants reported feeling or focus during 75% of the trials. Regarding brain activity, finger attention increased activation in somatosensory regions (primary sensory cortex, insula) and sensory integration regions (precuneus, dorsolateral prefrontal cortex). Exploratory analyses suggested that brain activation may be associated with CIPN severity. A larger sample size and accounting of confounding factors is needed to test for replication and to identify brain and interoceptive biomarkers to help improve the prediction, prevention, and treatment of CIPN.

Strength of spatial correlation between structural brain network connectivity and brain-wide patterns of proto-oncogene and neural network construction gene expression is associated with diffuse glioma survival.

Like other forms of neuropathology, gliomas appear to spread along neural pathways. Accordingly, our group and others have previously shown that brain network connectivity is highly predictive of glioma survival. In this study, we aimed to examine the molecular mechanisms of this relationship via imaging transcriptomics. We retrospectively obtained presurgical, T1-weighted MRI datasets from 669 adult patients, newly diagnosed with diffuse glioma. We measured brain connectivity using gray matter networks and coregistered these data with a transcriptomic brain atlas to determine the spatial co-localization between brain connectivity and expression patterns for 14 proto-oncogenes and 3 neural network construction genes. We found that all 17 genes were significantly co-localized with brain connectivity (p < 0.03, corrected). The strength of co-localization was highly predictive of overall survival in a cross-validated Cox Proportional Hazards model (mean area under the curve, AUC = 0.68 +/- 0.01) and significantly (p < 0.001) more so for a random forest survival model (mean AUC = 0.97 +/- 0.06). Bayesian network analysis demonstrated direct and indirect causal relationships among gene-brain co-localizations and survival. Gene ontology analysis showed that metabolic processes were overexpressed when spatial co-localization between brain connectivity and gene transcription was highest (p < 0.001). Drug-gene interaction analysis identified 84 potential candidate therapies based on our findings. Our findings provide novel insights regarding how gene-brain connectivity interactions may affect glioma survival.

Neuroimaging based biotypes for precision diagnosis and prognosis in cancer-related cognitive impairment.

Cancer related cognitive impairment (CRCI) is commonly associated with cancer and its treatments, yet the present binary diagnostic approach fails to capture the full spectrum of this syndrome. Cognitive function is highly complex and exists on a continuum that is poorly characterized by dichotomous categories. Advanced statistical methodologies applied to symptom assessments have demonstrated that there are multiple subclasses of CRCI. However, studies suggest that relying on symptom assessments alone may fail to account for significant differences in the neural mechanisms that underlie a specific cognitive phenotype. Treatment plans that address the specific physiologic mechanisms involved in an individual patient's condition is the heart of precision medicine. In this narrative review, we discuss how biotyping, a precision medicine framework being utilized in other mental disorders, could be applied to CRCI. Specifically, we discuss how neuroimaging can be used to determine biotypes of CRCI, which allow for increased precision in prediction and diagnosis of CRCI via biologic mechanistic data. Biotypes may also provide more precise clinical endpoints for intervention trials. Biotyping could be made more feasible with proxy imaging technologies or liquid biomarkers. Large cross-sectional phenotyping studies are needed in addition to evaluation of longitudinal trajectories, and data sharing/pooling is highly feasible with currently available digital infrastructures.

Cancer-related cognitive impairment in racial and ethnic minority groups: a scoping review.

PURPOSE: Disparities in cognitive function among racial and ethnic groups have been reported in non-cancer conditions, but cancer-related cognitive impairment (CRCI) in racial and ethnic minority groups is poorly understood. We aimed to synthesize and characterize the available literature about CRCI in racial and ethnic minority populations. METHODS: We conducted a scoping review in the PubMed, PsycInfo, and Cumulative Index to Nursing and Allied Health Literature databases. Articles were included if they were published in English or Spanish, reported cognitive functioning in adults diagnosed with cancer, and characterized the race or ethnicity of the participants. Literature reviews, commentaries, letters to the editor, and gray literature were excluded. RESULTS: Seventy-four articles met the inclusion criteria, but only 33.8% differentiated the CRCI findings by racial or ethnic subgroups. There were associations between cognitive outcomes and the participants' race or ethnicity. Additionally, some studies found that Black and non-white individuals with cancer were more likely to experience CRCI than their white counterparts. Biological, sociocultural, and instrumentation factors were associated with CRCI differences between racial and ethnic groups. CONCLUSIONS: Our findings indicate that racial and ethnic minoritized individuals  may be disparately affected by CRCI. Future research should use standardized guidelines for measuring and reporting the self-identified racial and ethnic composition of the sample; differentiate CRCI findings by racial and ethnic subgroups; consider the influence of structural racism in health outcomes; and develop strategies to promote the participation of members of racial and ethnic minority groups.

Clinical, psychosocial, and sociodemographic factors of sexual and gender minority groups with cancer: A systematic review.

PURPOSE: Psychosocial health varies depending on demographic and clinical factors and the social context in which individuals grow and live. Sexual and gender minority (SGM) populations experience health disparities due to systemic factors that privilege cisgender and heterosexual identities. We reviewed the literature on the psychosocial, sociodemographic, and clinical factors in SGM groups with cancer and described the associations among these factors. METHODS: We conducted a systematic review according to Fink's methodology and the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines in the PubMed, PsycInfo, Cumulative Index of Nursing and Allied Health Literature, and LGBTQ+ Life databases. Quantitative articles published in English or Spanish were included. Grey literature and studies with participants in hospice care were excluded. The quality of the publications was assessed with the Joanna Briggs Institute criticalappraisal tools. RESULTS: The review included 25 publications. In SGM groups, systemic cancer treatment was associated with worse psychosocial outcomes; and older age, employment, and higher income were associated with better psychosocial outcomes. CONCLUSIONS: SGM groups with cancer are different from their heterosexual cisgender peers in sociodemographic, psychosocial, and clinical factors. Clinical and sociodemographic factors are associated with psychosocial outcomes among SGM individuals with cancer.

Behavioral and biologic characteristics of cancer-related cognitive impairment biotypes.

Psychiatric diagnosis is moving away from symptom-based classification and towards multi-dimensional, biologically-based characterization, or biotyping. We previously identified three biotypes of chemotherapy-related cognitive impairment based on functional brain connectivity. In this follow-up study of 80 chemotherapy-treated breast cancer survivors and 80 non-cancer controls, we evaluated additional factors to help explain biotype expression: neurofunctional stability, brain age, apolipoprotein (APOE) genotype, and psychoneurologic symptoms. We also compared the discriminative ability of a traditional, symptom-based cognitive impairment definition with that of biotypes. We found significant differences in cortical brain age (F = 10.50, p < 0.001), neurofunctional stability (F = 2.83, p = 0.041), APOE e4 genotype (X2 = 7.68, p = 0.050), and psychoneurological symptoms (Pillai = 0.378, p < 0.001) across the three biotypes. The more resilient Biotype 2 demonstrated significantly higher neurofunctional stability compared to the other biotypes. Symptom-based classification of cognitive impairment did not differentiate biologic or other behavioral variables, suggesting that traditional categorization of cancer-related cognitive effects may miss important characteristics which could inform targeted treatment strategies. Additionally, biotyping, but not symptom-typing, was able to distinguish survivors with cognitive versus psychological effects. Our results suggest that Biotype 1 survivors might benefit from first addressing symptoms of anxiety and fatigue, Biotype 3 might benefit from a treatment plan which includes sleep hygiene, and Biotype 2 might benefit most from cognitive skills training or rehabilitation. Future research should include additional demographic and clinical information to further investigate biotype expression related to risk and resilience and examine integration of more clinically feasible imaging approaches.

Cisheteronormativity and its influence on the psychosocial experience of LGBTQ+ people with cancer: A qualitative systematic review.

OBJECTIVE: Cisheteronormativity refers to the relationship of heterosexual and cisgender privilege stemming from patriarchy. Although studies have shown that cisheteronormativity can impact health outcomes for lesbian, gay, bisexual, transgender, queer and other sexual, gender diverse, and gender nonconforming (LGBTQ+) people, the specific impact on cancer care has not been described. We synthesized the qualitative evidence on how cisheteronormativity impacts the psychosocial experience of LGBTQ+ people with cancer. METHODS: We conducted a historic search in the CINAHL, LGBT+ Health, PsycInfo, and PubMed databases. Qualitative studies that described the psychosocial experience of LGBTQ+ people with cancer were included. After appraising the quality of the publications, 11 articles were included. Then, we conducted inductive nominal coding, taxonomic analysis, and thematic synthesis. RESULTS: Two main themes emerged, (1) Cisheteronormativity as a social determinant of health, and (2) Cancer, sexual orientation, and gender: Associations and introjections. The themes comprise four categories and 13 subcategories that describe the impact of cisheteronormativity on the cancer experience of LGBTQ+ people. CONCLUSION: Cisheteronormativity within the healthcare system impacts the psychosocial experience of LGBTQ+ people with cancer. Understanding how these gender biases, norms, and social expectations impact the cancer experience is necessary to transform social norms and promote health equity.

Subjective cancer-related cognitive impairments and salience network connectivity in breast cancer survivors.

PURPOSE: Little is known about the neural basis of subjective cancer-related cognitive changes. The purpose of this study was to explore salience network connectivity in relation to subjective executive and memory dysfunction in breast cancer survivors compared to controls. METHODS: A retrospective cross-sectional analysis of neuroimaging, subjective cognitive, clinical, and demographic data in chemotherapy-treated primary breast cancer survivors compared to frequency matched controls was used. Functional connectivity within salience network hubs (anterior cingulate, bilateral insula) was determined using resting state functional MRI. Mann-Whitney U tests were used to evaluate group differences and Spearman's rho correlations were examined among the behavioral measures and salience network connectivity. RESULTS: We included 65 breast cancer survivors and 71 controls. Survivors demonstrated greater subjective executive dysfunction and memory complaints (p < .001) and lower salience network connectivity (p < .05) than controls. Executive functioning correlated with bilateral insula and left anterior cingulate connectivity (rho > - 0.29, p < .05). Distress did not correlate with salience network connectivity. CONCLUSION: These findings suggest that salience network connectivity may represent a biomarker of subjective cancer-related cognitive changes. IMPLICATIONS FOR CANCER SURVIVORS: Subjective cancer-related cognitive changes are common following treatment and associated with objective changes in brain connectivity.

Symptom Clusters Seen in Adult COVID-19 Recovery Clinic Care Seekers.

BACKGROUND: COVID-19 symptom reports describe varying levels of disease severity with differing periods of recovery and symptom trajectories. Thus, there are a multitude of disease and symptom characteristics clinicians must navigate and interpret to guide care. OBJECTIVE: To find natural groups of patients with similar constellations of post-acute sequelae of COVID-19 (PASC) symptoms. DESIGN: Cohort SETTING: Outpatient COVID-19 recovery clinic with patient referrals from 160 primary care clinics serving 36 counties in Texas. PATIENTS: Adult patients seeking COVID-19 recovery clinic care between November 15, 2020, and July 31, 2021, with laboratory-confirmed mild (not hospitalized), moderate (hospitalized), or severe (hospitalized with critical care) COVID-19. MAIN MEASURES: Demographics, COVID illness onset, and duration of persistent PASC symptoms via semi-structured medical assessments. KEY RESULTS: Four hundred forty-one patients (mean age 51.5 years; 295 [66.9%] women; 99 [22%] Hispanic, and 170 [38.5%] non-White, racial minority) met inclusion criteria. Using a k-medoids algorithm, we found that PASC symptoms cluster into two distinct groups: neuropsychiatric (N = 186) (e.g., subjective cognitive dysfunction) and pulmonary (N = 255) (e.g., dyspnea, cough). The neuropsychiatric cluster had significantly higher incidences of otolaryngologic (X2 = 14.3, p < 0.001), gastrointestinal (X2 = 6.90, p = 0.009), neurologic (X2 = 441, p < 0.001), and psychiatric sequelae (X2 = 40.6, p < 0.001) with more female (X2 = 5.44, p = 0.020) and younger age (t = 2.39, p = 0.017) patients experiencing longer durations of PASC symptoms before seeking care (t = 2.44, p = 0.015). Patients in the pulmonary cluster were more often hospitalized for COVID-19 (X2 = 3.98, p = 0.046) and had significantly higher comorbidity burden (U = 20800, p = 0.019) and pulmonary sequelae (X2 = 13.2, p < 0.001). CONCLUSIONS: Health services clinic data from a large integrated health system offers insights into the post-COVID symptoms associated with care seeking for sequelae that are not adequately managed by usual care pathways (self-management and primary care clinic visits). These findings can inform machine learning algorithms, primary care management, and selection of patients for earlier COVID-19 recovery referral. TRIAL REGISTRATION: N/A.

Remote assessment of cognitive dysfunction in hematologic malignancies using web-based neuropsychological testing.

BACKGROUND: Cognitive impairment is a frequent adverse effect of cancer and its therapies. As neuropsychological assessment is not often standard of care for patients with non-CNS disease, efficient, practical assessment tools are required to track cognition across the disease course. We examined cognitive functioning using a web-based cognitive testing battery to determine if it could detect differences between patients with cancer and controls. METHODS: We enrolled 22 patients with multiple myeloma (MM) or non-Hodgkin lymphoma (NHL) and 40 healthy controls (mean age = 56 ± 11 years, 52% male). Participants completed the BrainCheck cognitive testing battery and online versions of select measures from the Patient Reported Outcome Measures Information System (PROMIS) during a video conference. MANOVA was used to compare BrainCheck and PROMIS scores between groups controlling for age and sex. An exploratory linear regression analysis was conducted within the cancer group to determine potential contributors to cognitive functioning. RESULTS: All participants except for one control completed the online assessment measures without difficulty. Compared to controls, the cancer group demonstrated significantly lower scores in objective and subjective cognitive function, physical functioning, and social role performance and elevated fatigue scores. Corticosteroid treatment, immunotherapy, lower physical functioning, lower income, and older age significantly contributed to lower cognitive function (adjusted R2  = 0.925, F = 19.63, p = 0.002). CONCLUSION: Remote assessment of cognitive and psychosocial functioning is feasible with patients with cancer following treatments. The BrainCheck cognitive testing battery has the potential to detect differences in cognition between patients with cancer and controls.

Predicting overall survival in diffuse glioma from the presurgical connectome.

Diffuse gliomas are incurable brain tumors, yet there is significant heterogeneity in patient survival. Advanced computational techniques such as radiomics show potential for presurgical prediction of survival and other outcomes from neuroimaging. However, these techniques ignore non-lesioned brain features that could be essential for improving prediction accuracy. Gray matter covariance network (connectome) features were retrospectively identified from the T1-weighted MRIs of 305 adult patients diagnosed with diffuse glioma. These features were entered into a Cox proportional hazards model to predict overall survival with 10-folds cross-validation. The mean time-dependent area under the curve (AUC) of the connectome model was compared with the mean AUCs of clinical and radiomic models using a pairwise t-test with Bonferroni correction. One clinical model included only features that are known presurgery (clinical) and another included an advantaged set of features that are not typically known presurgery (clinical +). The median survival time for all patients was 134.2 months. The connectome model (AUC 0.88 ± 0.01) demonstrated superior performance (P < 0.001, corrected) compared to the clinical (AUC 0.61 ± 0.02), clinical + (AUC 0.79 ± 0.01) and radiomic models (AUC 0.75 ± 0.02). These findings indicate that the connectome is a feasible and reliable early biomarker for predicting survival in patients with diffuse glioma. Connectome and other whole-brain models could be valuable tools for precision medicine by informing patient risk stratification and treatment decision-making.

A Mouse Holder for Awake Functional Imaging in Unanesthetized Mice: Applications in 31P Spectroscopy, Manganese-Enhanced Magnetic Resonance Imaging Studies, and Resting-State Functional Magnetic Resonance Imaging.

Anesthesia is often used in preclinical imaging studies that incorporate mouse or rat models. However, multiple reports indicate that anesthesia has significant physiological impacts. Thus, there has been great interest in performing imaging studies in awake, unanesthetized animals to obtain accurate results without the confounding physiological effects of anesthesia. Here, we describe a newly designed mouse holder that is interfaceable with existing MRI systems and enables awake in vivo mouse imaging. This holder significantly reduces head movement of the awake animal compared to previously designed holders and allows for the acquisition of improved anatomical images. In addition to applications in anatomical T2-weighted magnetic resonance imaging (MRI), we also describe applications in acquiring 31P spectra, manganese-enhanced magnetic resonance imaging (MEMRI) transport rates and resting-state functional magnetic resonance imaging (rs-fMRI) in awake animals and describe a successful conditioning paradigm for awake imaging. These data demonstrate significant differences in 31P spectra, MEMRI transport rates, and rs-fMRI connectivity between anesthetized and awake animals, emphasizing the importance of performing functional studies in unanesthetized animals. Furthermore, these studies demonstrate that the mouse holder presented here is easy to construct and use, compatible with standard Bruker systems for mouse imaging, and provides rigorous results in awake mice.

Identifying Themes for Assessing Cancer-Related Cognitive Impairment: Topic Modeling and Qualitative Content Analysis of Public Online Comments.

BACKGROUND: Cancer-related cognitive impairment (CRCI) is a common and significant adverse effect of cancer and its therapies. However, its definition and assessment remain difficult due to limitations of currently available measurement tools. OBJECTIVE: This study aims to evaluate qualitative themes related to the cognitive effects of cancer to help guide development of assessments that are more specific than what is currently available. METHODS: We applied topic modeling and inductive qualitative content analysis to 145 public online comments related to cognitive effects of cancer. RESULTS: Topic modeling revealed 2 latent topics that we interpreted as representing internal and external factors related to cognitive effects. These findings lead us to hypothesize regarding the potential contribution of locus of control to CRCI. Content analysis suggested several major themes including symptoms, emotional/psychological impacts, coping, "chemobrain" is real, change over time, and function. There was some conceptual overlap between the 2 methods regarding internal and external factors related to patient experiences of cognitive effects. CONCLUSIONS: Our findings indicate that coping mechanisms and locus of control may be important themes to include in assessments of CRCI. Future directions in this field include prospective acquisition of free-text responses to guide development of assessments that are more sensitive and specific to cognitive function in patients with cancer.

Cognitive Impairment in Non-critical, Mild-to-Moderate COVID-19 Survivors.

IMPORTANCE: Previous studies of post-acute COVID-19 syndrome have focused on critical cases with severe disease. However, most cases are mild to moderate in disease severity. OBJECTIVE: We aimed to examine cognitive outcomes in cases of non-critical, mild-to-moderate COVID-19. Design, Setting, and Participants: In this cross-sectional study, we enrolled 72 adults aged 22 to 65 years in Central Texas who had non-critical, mild-to-moderate COVID-19 infection between 13 January 2021 and 20 April 2021. MAIN OUTCOMES AND MEASURES: We remotely administered cognitive-behavioral testing to determine the frequency of cognitive impairment and examine demographic, clinical, and psychosocial contributors to impairment. RESULTS: The frequency of objective cognitive impairment was 40%. The largest number of participants (24%) showed impairment on a measure of executive functioning. Attention and processing speed was more impaired in males (OR = 1.5, 95%CI = 0.23-2.9). Males endorsed lower adherence to social distancing guidelines (U = 590, p = 0.01), which was in turn associated with cognitive impairment across participants (r = -0.30, p = 0.01). Younger age was correlated with impairment (r = -0.26, p = 0.03) but was also associated with racial/ethnic minority status (r = -0.31, p = 0.01) and increased psychological symptoms (p < 0.04). Greater number of COVID-19 symptoms was correlated with lower subjective cognitive function (r = -0.38, p = 0.001) as well as psychosocial function (r > 0.24, p < 0.05). Moderate COVID-19 severity was associated with attention/processing speed impairment (r = 0.27, p = 0.03), increased pain (r = 0.31, p = 0.01), and higher number of COVID-19 symptoms (r = 0.32, p = 0.01). CONCLUSION AND RELEVANCE: Mild or moderate COVID-19 infection may be associated with cognitive impairments, especially in the domain of executive functioning. A subgroup of younger individuals may be more vulnerable to cognitive and psychosocial effects of COVID-19. HIGHLIGHTS: Question: How frequent is cognitive impairment among non-critical, mild-to-moderate COVID-19 survivors? FINDINGS: In this cross-sectional study of 72 adults, 40% demonstrated cognitive impairment, particularly in executive function. MEANING: Neurologic sequelae, such as cognitive impairment, may be common following COVID-19 infection.

Characteristics of Post-ICU and Post-COVID Recovery Clinics in 29 U.S. Health Systems.

The multifaceted long-term impairments resulting from critical illness and COVID-19 require interdisciplinary management approaches in the recovery phase of illness. Operational insights into the structure and process of recovery clinics (RCs) from heterogeneous health systems are needed. This study describes the structure and process characteristics of existing and newly implemented ICU-RCs and COVID-RCs in a subset of large health systems in the United States. DESIGN: Cross-sectional survey. SETTING: Thirty-nine RCs, representing a combined 156 hospitals within 29 health systems participated. PATIENTS: None. INTERVENTIONS: None. MEASUREMENT AND MAIN RESULTS: RC demographics, referral criteria, and operating characteristics were collected, including measures used to assess physical, psychologic, and cognitive recoveries. Thirty-nine RC surveys were completed (94% response rate). ICU-RC teams included physicians, pharmacists, social workers, physical therapists, and advanced practice providers. Funding sources for ICU-RCs included clinical billing (n = 20, 77%), volunteer staff support (n = 15, 58%), institutional staff/space support (n = 13, 46%), and grant or foundation funding (n = 3, 12%). Forty-six percent of RCs report patient visit durations of 1 hour or longer. ICU-RC teams reported use of validated scales to assess psychologic recovery (93%), physical recovery (89%), and cognitive recovery (86%) more often in standard visits compared with COVID-RC teams (psychologic, 54%; physical, 69%; and cognitive, 46%). CONCLUSIONS: Operating structures of RCs vary, though almost all describe modest capacity and reliance on volunteerism and discretionary institutional support. ICU- and COVID-RCs in the United States employ varied funding sources and endorse different assessment measures during visits to guide care coordination. Common features include integration of ICU clinicians, interdisciplinary approach, and focus on severe critical illness. The heterogeneity in RC structures and processes contributes to future research on the optimal structure and process to achieve the best postintensive care syndrome and postacute sequelae of COVID outcomes.