Retrospective case-control study to compare exoskeleton-assisted walking with standard care in subacute non-traumatic brain injury patients.

BACKGROUND: Advanced technologies are increasingly used to address impaired mobility after neurological insults, with growing evidence of their benefits for various populations. However, certain robotic devices have not been extensively investigated in specific conditions, limiting knowledge about optimal application for healthcare. OBJECTIVE: To compare effectiveness of conventional gait training with exoskeleton-assisted walking for non-traumatic brain injury during early stage rehabilitation. METHODS: Clinical evaluation data at admission and discharge were obtained in a retrospective case-control design. Patients received standard of care physical therapy either using Ekso GT or not. Within- or between-group statistical tests were performed to determine change over time and interventional differences. RESULTS: This study analyzed forty-nine individuals (33% female), 20 controls and 29 Ekso participants who were equivalent at baseline. Both groups improved in Functional Independence Measure scores and ambulation ability (p < .00001 and p < .001, respectively). Control subjects demonstrated significantly different distance walked and assistance level values at discharge from those who were treated with the exoskeleton (p < .01). CONCLUSION: Robotic locomotion is non-inferior for subacute functional recovery after non-traumatic brain injury. Conventional therapy produced larger gait performance gains during hospitalization. Further research is needed to understand specific factors influencing efficacy and the long-term implications after rehabilitation.

Dysautonomia, but Not Cardiac Dysfunction, Is Common in a Cohort of Individuals with Long COVID.

Despite the prevalence of dysautonomia in people with Long COVID, it is currently unknown whether Long COVID dysautonomia is routinely accompanied by structural or functional cardiac alterations. In this retrospective observational study, the presence of echocardiographic abnormalities was assessed. Left ventricular (LV) chamber sizes were correlated to diagnostic categories and symptoms via standardized patient-reported outcome (PRO) questionnaires. A total of 203 individuals with Long COVID without pre-existing cardiac disease and with available echocardiograms were included (mean age, 45 years; 67% female). Overall, symptoms and PRO scores for fatigue, breathlessness, quality of life, disability, anxiety and depression were not different between those classified with post-COVID dysautonomia (PCD, 22%) and those unclassified (78%). An LV internal diameter at an end-diastole z score < -2 was observed in 33 (16.5%) individuals, and stroke volume (SV) was lower in the PCD vs. unclassified subgroup (51.6 vs. 59.2 mL, 95% C.I. 47.1-56.1 vs. 56.2-62.3). LV end-diastolic volume (mean diff. (95% CI) -13 [-1--26] mL, p = 0.04) and SV (-10 [-1--20] mL, p = 0.03) were smaller in those individuals reporting a reduction in physical activity post-COVID-19 infection, and smaller LVMI was weakly correlated with worse fatigue (r = 0.23, p = 0.02). The majority of individuals with Long COVID report shared symptoms and did not demonstrate cardiac dysfunction on echocardiography.

Distinguishing features of long COVID identified through immune profiling.

Post-acute infection syndromes may develop after acute viral disease1. Infection with SARS-CoV-2 can result in the development of a post-acute infection syndrome known as long COVID. Individuals with long COVID frequently report unremitting fatigue, post-exertional malaise, and a variety of cognitive and autonomic dysfunctions2-4. However, the biological processes that are associated with the development and persistence of these symptoms are unclear. Here 275 individuals with or without long COVID were enrolled in a cross-sectional study that included multidimensional immune phenotyping and unbiased machine learning methods to identify biological features associated with long COVID. Marked differences were noted in circulating myeloid and lymphocyte populations relative to the matched controls, as well as evidence of exaggerated humoral responses directed against SARS-CoV-2 among participants with long COVID. Furthermore, higher antibody responses directed against non-SARS-CoV-2 viral pathogens were observed among individuals with long COVID, particularly Epstein-Barr virus. Levels of soluble immune mediators and hormones varied among groups, with cortisol levels being lower among participants with long COVID. Integration of immune phenotyping data into unbiased machine learning models identified the key features that are most strongly associated with long COVID status. Collectively, these findings may help to guide future studies into the pathobiology of long COVID and help with developing relevant biomarkers.

Remote Patient Monitoring of Blood Pressure Is Feasible Poststroke and Can Facilitate Triage of Care.

Background and Purpose: Strict blood pressure (BP) control is a universally accepted therapeutic intervention in the prevention of secondary stroke, yet this remains difficult when patients return home postinjury. This study aimed to investigate the application of the remote patient monitoring (RPM) of BP in patients after stroke, or who were at immediate risk of stroke, and the subsequent outcomes relating to triage and escalation of care. Methods: This was a single-center proof-of-concept study. Participants were patients aged 18 years and older with a diagnosis of stroke or who were at immediate risk of stroke. Patients were enrolled into the precision recovery program (PRP) and asked to assess their BP and heart rate daily and enter values into a MyCap application for the RPM program. These data were reviewed daily by an assigned PRP clinician, and weekly Zoom meetings were held with the patient. Care was triaged and escalated to a physician as indicated. Results: Twelve patients (5 [42%] female, aged mean [range] 63 [43-84] years) met the inclusion criteria and continued in the program for median (range) 136 (8-227) days. The median (range) number of excursions of BP above limits per participant was 19 (0-79) for systolic and 36 (0-104) for diastolic. A total of 16 triage events (median [range] 1 [0-3]) were initiated for escalation of care. Conclusions: This study demonstrated that RPM is feasible in patients poststroke or at immediate risk of stroke, and facilitates the triage of care when BP is elevated above recommended limits.

Distinguishing features of Long COVID identified through immune profiling.

SARS-CoV-2 infection can result in the development of a constellation of persistent sequelae following acute disease called post-acute sequelae of COVID-19 (PASC) or Long COVID 1-3 . Individuals diagnosed with Long COVID frequently report unremitting fatigue, post-exertional malaise, and a variety of cognitive and autonomic dysfunctions 1-3 ; however, the basic biological mechanisms responsible for these debilitating symptoms are unclear. Here, 215 individuals were included in an exploratory, cross-sectional study to perform multi-dimensional immune phenotyping in conjunction with machine learning methods to identify key immunological features distinguishing Long COVID. Marked differences were noted in specific circulating myeloid and lymphocyte populations relative to matched control groups, as well as evidence of elevated humoral responses directed against SARS-CoV-2 among participants with Long COVID. Further, unexpected increases were observed in antibody responses directed against non-SARS-CoV-2 viral pathogens, particularly Epstein-Barr virus. Analysis of circulating immune mediators and various hormones also revealed pronounced differences, with levels of cortisol being uniformly lower among participants with Long COVID relative to matched control groups. Integration of immune phenotyping data into unbiased machine learning models identified significant distinguishing features critical in accurate classification of Long COVID, with decreased levels of cortisol being the most significant individual predictor. These findings will help guide additional studies into the pathobiology of Long COVID and may aid in the future development of objective biomarkers for Long COVID.

Mild respiratory COVID can cause multi-lineage neural cell and myelin dysregulation.

COVID survivors frequently experience lingering neurological symptoms that resemble cancer-therapy-related cognitive impairment, a syndrome for which white matter microglial reactivity and consequent neural dysregulation is central. Here, we explored the neurobiological effects of respiratory SARS-CoV-2 infection and found white-matter-selective microglial reactivity in mice and humans. Following mild respiratory COVID in mice, persistently impaired hippocampal neurogenesis, decreased oligodendrocytes, and myelin loss were evident together with elevated CSF cytokines/chemokines including CCL11. Systemic CCL11 administration specifically caused hippocampal microglial reactivity and impaired neurogenesis. Concordantly, humans with lasting cognitive symptoms post-COVID exhibit elevated CCL11 levels. Compared with SARS-CoV-2, mild respiratory influenza in mice caused similar patterns of white-matter-selective microglial reactivity, oligodendrocyte loss, impaired neurogenesis, and elevated CCL11 at early time points, but after influenza, only elevated CCL11 and hippocampal pathology persisted. These findings illustrate similar neuropathophysiology after cancer therapy and respiratory SARS-CoV-2 infection which may contribute to cognitive impairment following even mild COVID.

Gamified Neurorehabilitation Strategies for Post-stroke Motor Recovery: Challenges and Advantages.

PURPOSE OF REVIEW: Stroke is the leading cause of permanent motor disability in the United States (US), but there has been little progress in developing novel, effective strategies for treating post-stroke motor deficits. The past decade has seen the rapid development of many promising, gamified neurorehabilitation technologies; however, clinical adoption remains limited. The purpose of this review is to evaluate the recent literature surrounding the adoption and use of gamification in neurorehabilitation after stroke. RECENT FINDINGS: Gamification of neurorehabilitation protocols is both feasible and effective. Deployment strategies and scalability need to be addressed with more rigor. Relationship between engaged time on task and rehabilitation outcomes should be explored further as it may create benefits beyond repetitive movement. As gamification becomes a more common and feasible way of delivering exercise-based therapies, additional benefits of gamification are emerging. In spite of this, questions still exist about scalability and widespread clinical adoption.

Mild respiratory SARS-CoV-2 infection can cause multi-lineage cellular dysregulation and myelin loss in the brain.

Survivors of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection frequently experience lingering neurological symptoms, including impairment in attention, concentration, speed of information processing and memory. This long-COVID cognitive syndrome shares many features with the syndrome of cancer therapy-related cognitive impairment (CRCI). Neuroinflammation, particularly microglial reactivity and consequent dysregulation of hippocampal neurogenesis and oligodendrocyte lineage cells, is central to CRCI. We hypothesized that similar cellular mechanisms may contribute to the persistent neurological symptoms associated with even mild SARS-CoV-2 respiratory infection. Here, we explored neuroinflammation caused by mild respiratory SARS-CoV-2 infection - without neuroinvasion - and effects on hippocampal neurogenesis and the oligodendroglial lineage. Using a mouse model of mild respiratory SARS-CoV-2 infection induced by intranasal SARS-CoV-2 delivery, we found white matter-selective microglial reactivity, a pattern observed in CRCI. Human brain tissue from 9 individuals with COVID-19 or SARS-CoV-2 infection exhibits the same pattern of prominent white matter-selective microglial reactivity. In mice, pro-inflammatory CSF cytokines/chemokines were elevated for at least 7-weeks post-infection; among the chemokines demonstrating persistent elevation is CCL11, which is associated with impairments in neurogenesis and cognitive function. Humans experiencing long-COVID with cognitive symptoms (48 subjects) similarly demonstrate elevated CCL11 levels compared to those with long-COVID who lack cognitive symptoms (15 subjects). Impaired hippocampal neurogenesis, decreased oligodendrocytes and myelin loss in subcortical white matter were evident at 1 week, and persisted until at least 7 weeks, following mild respiratory SARS-CoV-2 infection in mice. Taken together, the findings presented here illustrate striking similarities between neuropathophysiology after cancer therapy and after SARS-CoV-2 infection, and elucidate cellular deficits that may contribute to lasting neurological symptoms following even mild SARS-CoV-2 infection.

Post-acute COVID-19 Syndrome Negatively Impacts Physical Function, Cognitive Function, Health-Related Quality of Life, and Participation.

OBJECTIVE: This report describes persistent symptoms associated with post-acute COVID-19 syndrome (PACS) and the impact of these symptoms on physical function, cognitive function, health-related quality of life, and participation. DESIGN: This study used a cross-sectional observational study design. Patients attending Mount Sinai's post-acute COVID-19 syndrome clinic completed surveys containing patient-reported outcomes. RESULTS: A total of 156 patients completed the survey, at a median (range) time of 351 days (82-457 days) after COVID-19 infection. All patients were prevaccination. The most common persistent symptoms reported were fatigue (n = 128, 82%), brain fog (n = 105, 67%), and headache (n = 94, 60%). The most common triggers of symptom exacerbation were physical exertion (n = 134, 86%), stress (n = 107, 69%), and dehydration (n = 77, 49%). Increased levels of fatigue (Fatigue Severity Scale) and dyspnea (Medical Research Council) were reported, alongside reductions in levels of regularly completed physical activity. Ninety-eight patients (63%) scored for at least mild cognitive impairment (Neuro-Qol), and the domain of the EuroQol: 5 dimension, 5 level most impacted was Self-care, Anxiety/Depression and Usual Activities. CONCLUSIONS: Persistent symptoms associated with post-acute COVID-19 syndrome seem to impact physical and cognitive function, health-related quality of life, and participation in society. More research is needed to further clarify the relationship between COVID-19 infection and post-acute COVID-19 syndrome symptoms, the underlying mechanisms, and treatment options.

Remote Patient Monitoring Identifies the Need for Triage in Patients with Acute COVID-19 Infection.

Introduction: Telehealth was frequently used in the provision of care and remote patient monitoring (RPM) during the COVID-19 pandemic. The Precision Recovery Program (PRP) remotely monitored and supported patients with COVID-19 in their home environment. Materials and Methods: This was a single-center retrospective cohort study reviewing data acquired from the PRP clinical initiative. Results: Of the 679 patients enrolled in the PRP, 156 patients were screened by a clinician following a deterioration in symptoms and vital signs on a total of 240 occasions, and included in the analyses. Of these 240 occasions, 162 (67%) were escalated to the PRP physician. Thirty-six patients were referred to emergency department, with 12 (7%) admitted to the hospital. The most common risk factors coinciding with hospital admissions were cardiac (67%), age >65 (42%), obesity (25%), and pulmonary (17%). The most common symptoms reported that triggered a screening event were dyspnea/tachypnea (27%), chest pain (14%), and gastrointestinal issues (8%). Vital signs that commonly triggered a screening event were pulse oximetry (15%), heart rate (11%), and temperature (9%). Discussion: Common factors (risk factors, vital signs, and symptoms) among patients requiring screening, triage, and hospitalization were identified, providing clinicians with further information to support decision making when utilizing RPM in this cohort. Conclusion: A clinician-led RPM program for patients with acute COVID-19 infection provided supportive care and screening for deterioration. Similar models should be considered for implementation in COVID-19 cohorts and other conditions at risk of rapid clinical deterioration in the home setting.

Pain Reduction after Short Exposure to Virtual Reality Environments in People with Spinal Cord Injury.

Emerging literature suggests that virtual reality (VR) may be a viable therapy for neuropathic pain (NP). This pilot study aimed to investigate the immediate effect of VR in reducing NP in people with spinal cord injury (SCI). Eight individuals with chronic NP after SCI were recruited and underwent consecutive exposure to scenery and somatic virtual environments (VE). The numeric rating scale (NRS) was used to assess pain before and after exposure to each VE. The Immersive Tendencies Questionnaire (ITQ) and Presence Questionnaire (UQO-PQ) were used to investigate the interaction between reported pain relief post-intervention with immersion and presence. There was a significant reduction in pain levels (5.1 ± 0.4, mean ± SEM) after short exposure to the scenery (3.1 ± 0.7, p = 0.04) and somatic VE (3.0 ± 0.7, p = 0.04), with no difference between intervention types (p = 0.56). There was a statistically significant negative correlation between the total ITQ score and the change in NRS after the scenery VR intervention (rs = 0.743, p = 0.035). PQ scores showed no significant correlation with changes in pain following either intervention type. We found that short-term exposure to VR environments results in a reduction in chronic NP intensity in people with SCI.

Use of Fitbit Technology Does Not Impact Health Biometrics in a Community of Older Adults.

Introduction: To evaluate if the offering of Fitbit technology led to changes in cardiovascular health metrics in a cohort of older adults. Methods: A retrospective cohort study was developed in two community-embedded health monitoring sites, located in aggregate housing communities for older adults in Westchester County, NY. Participants included older adults (55 years or older) enrolled in the Telehealth Intervention Programs for Seniors (TIPS) initiative, a community-embedded remote patient monitoring initiative. Weekly blood pressure, heart rate, weight, and blood oxygenation were taken on all participants. For participants who accepted a Fitbit Zip device, a weekly step count was also collected. Results: Ninety-four TIPS participants were offered Fitbit technology. Thirty participants accepted the technology and used it for a minimum of 6 months. No significant differences in any of the regularly acquired biometrics were noted between Fitbit users and non-Fitbit users. Across all participants, regardless of Fitbit use, there was a significant decrease in systolic blood pressure (SBP) over time. Conclusions: Neither Fitbit Zip ownership or compliance to Fitbit Zip usage influenced any of the biometrics taken as part of the TIPS. However, participation in the TIPS initiative may have an overall positive effect on SBP in older adults.

Remote Patient Monitoring for Home Management of Coronavirus Disease 2019 in New York: A Cross-Sectional Observational Study.

Background: Coronavirus disease 2019 (COVID-19) poses a global public health emergency, overwhelming health systems worldwide and forcing rapid adoption of telemedicine strategies. Introduction: The COVID-19 Precision Recovery Program (PRP) is a remote patient monitoring (RPM) clinical program that was deployed by a New York health system to perform physiologic and symptomatic monitoring for patients with confirmed or suspected COVID-19 diagnoses. Methods: The present cross-sectional descriptive study reports retrospective data collected from the PRP during the COVID-19 crisis in New York. Results: One hundred twelve patients were included; mean (standard deviation) age was 49 (17.6) years and 60.7% were female. Most prevalent reported comorbidities were hypertension (36.3%), hypercholesterolemia (26.5%), and diabetes (17.7%). Less than half (44.6%) had a positive polymerase chain reaction COVID test (PCR-test), 33% had an unknown COVID status, and 17.9% had a negative test result. The most commonly reported symptoms included dyspnea (55.4%) and anxiety (55.4%). Anxiety was ranked as the most severe symptom (9.8%), followed by difficulty concentrating (4.5%). Symptom presentation did not significantly differ based on PCR-test status. Discussion: RPM can be a valuable tool for delivering care to patients with confirmed or suspected COVID-19 diagnoses. Considering similarities in symptom presentation between PCR-test statuses, access to COVID-related clinical care should not be based on PCR-test results. Conclusions: RPM has strong potential to assist in the effective management of suspected COVID-19 patients.