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To characterize the functional impairments of a cohort of patients undergoing inpatient rehabilitation after surviving severe COVID-19 illness, in order to better understand the ongoing needs of this patient population. This study consisted of a retrospective chart review of consecutive patients hospitalized for COVID-19 and admitted to a regional inpatient rehabilitation hospital from April 29th to May 22nd, 2020. Patient demographics, clinical characteristics and complications from acute hospitalization were examined. Measures of fall risk (Berg Balance Scale), endurance (6 Minute Walk Test), gait speed (10 Meter Walk Test), mobility (transfer and ambulation independence), cognition, speech and swallowing (American Speech and Hearing Association National Outcomes Measurement System Functional Communication Measures) were assessed at rehabilitation admission and discharge. The study population included 29 patients and was 70% male, 58.6% white and with a mean age of 59.5. The mean length of acute hospitalization was 32.2 days with a mean of 18.7 days intubated. Patients spent a mean of 16.7 days in inpatient rehabilitation and 90% were discharged home. Patients demonstrated significant improvement from admission to discharge in measures of fall risk, endurance, gait speed, mobility, cognition, speech and swallowing, (p< 0.05). At discharge, a significant portion of the population continued to deficits in cognition (attention 37%; memory 28%; problem solving 28%), balance (55%) and gait speed (97%). Patients admitted to inpatient rehabilitation after hospitalization with COVID-19 demonstrated deficits in mobility, cognition, speech and swallowing at admission and improved significantly in all of these domains by discharge. However, a significant number of patients exhibited residual deficits at discharge highlighting the post-acute care needs of this patient population.

Pharmacological management of neurobehavioral disorders following traumatic brain injury (TBI) is common practice. However, the evidence available to guide this practice remains sparse. This review summarizes, in brief, the state of knowledge, organized via a time continuum from injury as well as by symptom complex. The areas of neuroprotection, hypo-arousal, attention and memory deficits, aggression, agitation, depression, and mania are reviewed. The literature was searched with PubMed on the terms \"traumatic brain injury\" or \"brain injury\" with \"pharmacology\" (and the symptoms according to which this review is arranged). Additional searches were conducted with the specific symptoms as search terms, crossed with the therapeutic agents or drug classes discussed. Where a paucity of prospective data exists, case reports and retrospective studies are included. Studies to date have yielded minimal positive evidence for enhancing function, memory, and behavior after TBI. No single agent likely will become sentinel in the recovery process, and combination therapy in the acute and postacute settings are required. A need exists to further define the role of psychopharmacology in postacute TBI medicine and the specific characteristics of subpopulations who might benefit.

Gaseous molecules have been increasingly explored for therapeutic development. Here, following an analytical background introduction, a systematic review of medical gas research is presented, focusing on tissue protections, mechanisms, data tangibility, and translational challenges. The pharmacological efficacies of carbon monoxide (CO) and xenon (Xe) are further examined with emphasis on intracellular messengers associated with cytoprotection and functional improvement for the CNS, heart, retina, liver, kidneys, lungs, etc. Overall, the outcome supports the hypothesis that readily deliverable “biological gas” (CO, H2, H2S, NO, O2, O3, and N2O) or “noble gas” (He, Ar, and Xe) treatment may preserve cells against common pathologies by regulating oxidative, inflammatory, apoptotic, survival, and/or repair processes. Specifically, CO, in safe dosages, elicits neurorestoration via igniting sGC/cGMP/MAPK signaling and crosstalk between HO‐CO, HIF‐1α/VEGF, and NOS pathways. Xe rescues neurons through NMDA antagonism and PI3K/Akt/HIF‐1α/ERK activation. Primary findings also reveal that the need to utilize cutting‐edge molecular and genetic tactics to validate mechanistic targets and optimize outcome consistency remains urgent; the number of neurotherapeutic investigations is limited, without published results from large in vivo models. Lastly, the broad‐spectrum, concurrent multimodal homeostatic actions of medical gases may represent a novel pharmaceutical approach to treating critical organ failure and neurotrauma. This systematic review is focused on tissue protections, mechanisms, data qualities, and translational challenges of experimental gas therapies. The outcome suggests that biological/noble gases in safe dosages preserve cells by modulating oxidative, inflammatory, apoptotic, survival, and/or repair processes; it remains urgent to validate therapeutic targets via cutting‐edge molecular/genetic technologies. Gas agents may be developed to treat organ failure and neurotrauma.

Physicians and other healthcare professionals are often the end users of medical innovation; however, they are rarely involved in the beginning design stages. This often results in ineffective healthcare solutions with poor adoption rates. At the early design stage, innovation would benefit from input from healthcare professionals. This report describes the first-ever rehabilitation hackathon—an interdisciplinary and competitive team event aimed at accelerating and improving healthcare solutions and providing an educational experience for participants. Hackathons are gaining traction as a way to accelerate innovation by bringing together a diverse group of interdisciplinary professionals from different industries who work collaboratively in teams and learn from each other, focus on a specific problem (“pain point”), develop a solution using design thinking techniques, pitch the solution to participants, gather fast feedback and quickly alter the prototype design (“pivoting”). 102 hackers including 19 (18.6 %) physicians and other professionals participated, and over the course of 2 days worked in teams, pitched ideas and developed design prototypes. Three awards were given for prototypes that may improve function in persons with disabilities. 43 hackers were women (42.2 %) and 59 men (57.8 %); they ranged in age from 16 to 79 years old; and, of the 75 hackers who reported their age, 63 (84 %) were less than 40 years old and 12 (16 %) were 40 years or older. This report contributes to the emerging literature on healthcare hackathons as a means of providing interdisciplinary education and training and supporting innovation.

[18F]AV-1451 (aka 18F-Flortaucipir, [18F]T807) was developed for positron-emission tomography (PET) imaging of paired helical filaments of hyperphosphorylated tau, which are of interest in a range of neuropathologies, including traumatic brain injury (TBI). Magnetic resonance imaging (MRI) techniques like diffusion tensor imaging (DTI) and resting state functional connectivity assess structural and functional characteristics of the brain, complementing the molecular information that can be obtained by PET. The goal herein was to explore the utility of such multi-modal imaging in a case series based on a population of TBI subjects. This study probes the interrelationship between tau deposition, white matter integrity, and gray matter functional connectivity across the spectrum of TBI. Nineteen subjects (11 controls, five former contact sports athletes, one automotive accident, and two with military-related injury) underwent [18F]AV-1451 PET and magnetic resonance scanning procedures. [18F]AV-1451 distribution volume ratio (DVR) was estimated using the Logan method and the cerebellum as a reference region. Diffusion tractography images and fractional anisotropy (FA) images were generated using diffusion toolkit and FSL. Resting-state functional MRI (fMRI) analysis was based on a graph theory metric, namely weighted degree centrality. TBI subjects showed greater heterogeneity in [18F]AV-1451 DVR when compared with control subjects. In a subset of TBI subjects, areas with high [18F]AV-1451 binding corresponded with increased FA and diminished white matter tract density in DTI. Functional MRI results exhibited an increase in functional connectivity, particularly among local connections, in the areas where tau aggregates were more prevalent. In a case series of a diverse group of TBI subjects, brain regions with elevated tau burden exhibited increased functional connectivity as well as decreased white matter integrity. These findings portray molecular, microstructural, and functional corollaries of TBI that spatially coincide and can be measured in the living human brain using noninvasive neuroimaging techniques.

A 16-year-old girl was seen in the sports concussion clinic because of headache, dizziness, balance problems, fatigue, irritability, and difficulties with sleep and concentration after she had head trauma during a sailboat race. A diagnosis and management decisions were made.

Diffusion MRI (dMRI) data acquired on different scanners varies significantly in its content throughout the brain even if the acquisition parameters are nearly identical. Thus, proper harmonization of such data sets is necessary to increase the sample size and thereby the statistical power of neuroimaging studies. In this paper, we present a novel approach to harmonize dMRI data (the raw signal, instead of dMRI derived measures such as fractional anisotropy) using rotation invariant spherical harmonic (RISH) features embedded within a multi-modal image registration framework. All dMRI data sets from all sites are registered to a common template and voxel-wise differences in RISH features between sites at a group level are used to harmonize the signal in a subject-specific manner. We validate our method on diffusion data acquired from seven different sites (two GE, three Philips, and two Siemens scanners) on a group of age-matched healthy subjects. We demonstrate the efficacy of our method by statistically comparing diffusion measures such as fractional anisotropy, mean diffusivity and generalized fractional anisotropy across these sites before and after data harmonization. Validation was also done on a group oftest subjects, which were not used to “learn” the harmonization parameters. We also show results using TBSS before and after harmonization for independent validation of the proposed methodology. Using synthetic data, we show that any abnormality in diffusion measures due to disease is preserved during the harmonization process. Our experimental results demonstrate that, for nearly identical acquisition protocol across sites, scanner-specific differences in the signal can be removed using the proposed method in a model independent manner.

Cross-sectional approaches to outcome assessment may not adequately capture heterogeneity in recovery after traumatic brain injury (TBI). Using latent class mixed models (LCMM), a data-driven analytic that identifies groups of patients with similar trajectories, we identified distinct 6 month functional recovery trajectories in a large cohort (n = 1046) of adults 18–70 years of age with complicated mild to severe TBI who participated in the Citicoline Brain Injury Treatment Trial (COBRIT). We used multinomial logistic fixed effect models and backward elimination, forward selection, and forward stepwise selection with several stopping rules to explore baseline predictors of functional recovery trajectory. Based on statistical and clinical considerations, the seven-class model was deemed superior. Visualization of these seven functional recovery trajectories revealed that each trajectory class started at one of three recovery levels at 1 month, which, for ease of reference we labeled groups A–C: Group A, good recovery (two classes; A1 and A2); Group B, moderate disability (two classes; B1 and B2); and Group C, severe disability (three classes; C1, C2, and C3). By 6 months, these three groups experienced dramatically divergent trajectories. Group A experienced stable good recovery (A1, n = 115) or dramatic decline (A2, n = 4); Group B experienced rapid complete recovery (B1, n = 71) or gradual recovery (B2, n = 742); Group C experienced dramatic rapid recovery (C1, n = 12), no recovery (C2, n = 91), or death (C3, n = 11). Trajectory class membership was not predicted by citicoline treatment (p = 0.57). The models identified demographic, pre-injury, and injury-related predictors of functional recovery trajectory, including: age, race, education, pre-injury employment, pre-injury diabetes, pre-injury psychiatric disorder, site, Glasgow Coma Scale (GCS) score, post-traumatic amnesia, TBI mechanism, major extracranial injury, hemoglobin, and acute computed tomographic (CT) findings. GCS was the most consistently selected predictor across all models. All models also selected at least one demographic or pre-injury medical predictor. LCMM successfully identified dramatically divergent, clinically meaningful 6 month recovery trajectories with utility to inform clinical trial design.

The adult rodent spinal cord presents an inhibitory environment for donor cell survival, impeding efficiency for xenograft-based modeling of gliomas. We postulated that mild thermal preconditioning may influence the fate of the implanted tumor cells. To test this hypothesis, high-grade human astrocytoma G55 and U87 cells were cultured under 37°C and 38.5°C to mimic regular experimental or core body temperatures of rodents, respectively. In vitro, the 38.5°C-conditioned cells, relative to 37°C, grew slightly faster. Compared to U87 cells, G55 cells demonstrated a greater response to the temperature difference. Hyperthermal culture markedly increased production of Hsp27 in most G55 cells, but only promoted transient expression of cancer stem cell marker CD133 in a small cell subpopulation. We subsequently transplanted G55 cells following 37°C or 38.5°C culture into the C2 or T10 spinal cord of adult female immunodeficient rats (3 rats/each locus/per temperature; total: 12 rats). Systematic analyses revealed that 38.5°C-preconditioned G55 cells grew more malignantly at either C2 or T10 as determined by tumor size, outgrowth profile, resistance to bolus intratumor administration of 5-fluorouracil (0.1 μmol), and posttumor survival (p < 0.05; n = 6/group). Therefore, thermal preconditioning of glioma cells may be an effective way to influence the in vitro and in vivo oncological contour of glioma cells. Future studies are needed for assessing the potential oncogenic modifying effect of hyperthermia regimens on glioma cells.

[...]recent progress in characterising specific consequences and the availability of longitudinal studies of outcomes are providing the basis for improved understanding of TBI sequelae, as highlighted in two Series papers on TBI in The Lancet Neurology.1,2 Meyfroidt and colleagues1 have focused on the puzzling clinical syndrome of paroxysmal sympathetic hyperactivity (PSH), a specific consequence of severe brain injury, especially TBI, that can last for weeks to months after injury, while Wilson and colleagues2 have reviewed the growing body of evidence emphasising that TBI should be viewed as a chronic health condition with lifelong consequences for many patients. [...]there is a wide range in reported incidences of PSH; a further challenge to efforts to understand the epidemiology of PSH is that, for many patients, symptoms are unmasked only when analgesics are stopped upon transfer from an intensive care unit (ICU) to a rehabilitation setting. The recent proposal of an excitatory:inhibitory ratio model might add a construct from which to investigate this dysfunction physiologically.5 Few randomised controlled trials of interventions for PSH exist, and treatment decisions are largely based on clinical experience. [...]several medications proposed to treat PSH, reported in case series, such as opioids and α2-adrenergic drugs,1 might have sedative effects and therefore affect progress if used in the rehabilitation setting. Most worrisome is the growing recognition that CTE could be the result of subconcussive blows and is not solely linked to clinically apparent concussions. [...]population-wide effects on outcome are unclear but concerning.