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BackgroundLittle is known regarding long-term outcomes of patients hospitalized with COVID-19.MethodsWe conducted a prospective study of 6-month outcomes of hospitalized COVID-19 patients. Patients with new neurological complications during hospitalization who survived were propensity score-matched to COVID-19 survivors without neurological complications hospitalized during the same period. The primary 6-month outcome was multivariable ordinal analysis of the modified Rankin Scale(mRS) comparing patients with or without neurological complications. Secondary outcomes included: activities of daily living (ADLs;Barthel Index), telephone Montreal Cognitive Assessment and Neuro-QoL batteries for anxiety, depression, fatigue and sleep.ResultsOf 606 COVID-19 patients with neurological complications, 395 survived hospitalization and were matched to 395 controls; N=196 neurological patients and N=186 controls completed follow-up. Overall, 346/382 (91%) patients had at least one abnormal outcome: 56% had limited ADLs, 50% impaired cognition, 47% could not return to work and 62% scored worse than average on ≥1 Neuro-QoL scale (worse anxiety 46%, sleep 38%, fatigue 36%, and depression 25%). In multivariable analysis, patients with neurological complications had worse 6-month mRS (median 4 vs. 3 among controls, adjusted OR 2.03, 95%CI 1.22-3.40, P=0.01), worse ADLs (aOR 0.38, 95%CI 0.29-0.74, P=0.01) and were less likely to return to work than controls (41% versus 64%, P=0.04). Cognitive and Neuro-QOL metrics were similar between groups.ConclusionsAbnormalities in functional outcomes, ADLs, anxiety, depression and sleep occurred in over 90% of patients 6-months after hospitalization for COVID-19. In multivariable analysis, patients with neurological complications during index hospitalization had significantly worse 6-month functional outcomes than those without.

Primary objective: Excessive accumulation of amyloid beta (Aβ) and tau have been observed in older individuals with chronic neurological symptoms related to a traumatic brain injury (TBI), yet little is known about the possible role of Aβ in younger active duty service members following a TBI. The purpose of the study was to determine if Aβ 40 or 42 related to sustaining a TBI or to chronic neurological symptoms in a young cohort of military personnel. Research design: This was a cross-sectional study of active duty service members who reported sustaining a TBI and provided self-report of neurological and psychological symptoms and provided blood. Methods and procedures: An ultrasensitive single-molecule enzyme-linked immunosorbent assay was used to compare concentrations of Aβ in active duty service members with (TBI+; n = 53) and without (TBI–; n = 18) a history of TBI. Self-report and medical history were used to measure TBI occurrence and approximate the number of total TBIs and the severity of TBIs sustained during deployment. Main outcomes and results: This study reports that TBI is associated with higher concentrations of Aβ40 (F 1,68 = 6.948, p = 0.009) and a lower ratio of Aβ42/Aβ40 (F 1,62 = 5.671, p = 0.020). These differences remained significant after controlling for co-morbid symptoms of post-traumatic stress disorder and depression. Conclusions: These findings suggest that alterations in Aβ relate to TBIs and may contribute to chronic neurological symptoms.

Whole transcriptome analysis provides an unbiased examination of biological activity, and likely, unique insight into the mechanisms underlying posttraumatic stress disorder (PTSD) and comorbid depression and traumatic brain injury. This study compared gene-expression profiles in military personnel with PTSD (n=28) and matched controls without PTSD (n=27) using HG-U133 Plus 2.0 microarrays (Affymetrix), which contain 54,675 probe sets representing more than 38,500 genes. Analysis of expression profiles revealed 203 differentially expressed genes in PTSD, of which 72% were upregulated. Using Partek Genomics Suite 6.6, differentially expressed transcription clusters were filtered based on a selection criterion of ≥1.5 relative fold change at a false discovery rate of ≤5%. Ingenuity Pathway Analysis (Qiagen) of the differentially expressed genes indicated a dysregulation of genes associated with the innate immune, neuroendocrine, and NF-κB systems. These findings provide novel insights that may lead to new pharmaceutical agents for PTSD treatments and help mitigate mental and physical comorbidity risk.

There is a growing interest in the effectiveness of mindfulness meditation for sleep disturbed populations. Our study sought to evaluate the effect of mindfulness meditation interventions on sleep quality. To assessTo assess for relative efficacy, comparator groups were restricted to specific active controls (such as evidenced-based sleep treatments) and nonspecific active controls (such as time/attention-matched interventions to control for placebo effects), which were analyzed separately. From 3303 total records, 18 trials with 1654 participants were included. We determined the strength of evidence using four domains (risk of bias, directness of outcome measures, consistency of results, and precision of results). At post-treatment and follow-up, there was low strength of evidence that mindfulness meditation interventions had no effect on sleep quality compared with specific active controls (ES 0.03 [95% CI −0.43–0.49]) and (ES −0.14 [95% CI −0.62–0.34]) respectively. Additionally, there was moderate strength of evidence that mindfulness meditation interventions significantly improved sleep quality compared with nonspecific active controls at post-intervention (ES 0.33 [95% CI 0.17–0.48]) and at follow-up (ES 0.54 [95% CI 0.24–0.84]). These preliminary findings suggest that mindfulness meditation may be effective in treating some aspects of sleep disturbance. Further research is warranted.

Injury to the meninges is not uncommon after traumatic brain injury (TBI), yet minimal research has been directed toward understanding the relevant biology. After a concussive event, the meninges are observed to abnormally enhance on post-contrast magnetic resonance imaging (MRI) in some patients, but not all. The aim of this work is to identify genes differentially expressed in patients with meningeal injury. Patients presenting to the emergency room with suspected TBI received a standard research MRI and blood draw within 48 h of injury. Two groups of patients were included: those with and without abnormal enhancement of the meninges on post-contrast MRI, both without other imaging findings. Groups were compared on microarray gene expression in peripheral blood samples using Affymetrix (Santa Clara, CA) and Partek Genomics Suite (Partek, Inc., St. Louis, MO) software (false discovery rate

Older age consistently relates to a lesser ability to fully recover from a traumatic brain injury (TBI); however, there is limited data to explicate the nature of age-related risks. This study was undertaken to determine the relationship of age on gene-activity following a TBI, and how this biomarker relates to changes in neuroimaging findings. A younger group (between the ages of 19-35 years), and an older group (between the ages of 60-89 years) were compared on global gene-activity within 48 hours following a TBI, and then at follow-up within 1-week. At each time-point gene-expression profiles, and imaging findings from magnetic resonance imaging (MRI) and computed tomography (CT) were obtained and compared. The younger group was found to have greater gene expression of inflammatory regulatory genes at 48 hours and 1 week in genes such as basic leucine zipper transcription factor 2 (BACH2), leucine rich repeat neuronal 3 (LRRN3) and lymphoid enhancer-binding factor 1 (LEF1) compared to the older group. In the older group, there was increased activity in genes within S100 family, including calcium binding protein P (S100P) and S100 calcium binding protein A8 (S100A8), which previous studies have linked to poor recovery from TBI. The older group also had reduced activity of the noggin (NOG) gene, which is a member of the transforming growth factor-β (TGF-β) superfamily and is linked to neuro-recovery and neuro-regeneration compared to the younger group. We link these gene-expression findings that were validated to neuroimaging, reporting that in the older group with a MRI finding of TBI related damage, there was a lesser likelihood to then have a negative MRI finding at follow-up compared to the younger group. Together, these data indicate that age impacts gene activity following a TBI, and suggests that this differential activity related to immune regulation and neuro-recovery contributes to a lesser likelihood of neuronal recovery in older patients as indicated through neuroimaging.

OBJECTIVE: To determine changes in global gene expression in peripheral leukocytes in the acute and subacute periods following a sports-related concussion in athletes. SETTING: Samples were collected at 2 universities in Rochester, New York. PARTICIPANTS: Fifteen contact sport athletes who experienced a sports-related concussion, and 16 nonconcussed teammates served as controls. DESIGN: Blood samples were collected at the start of the season (baseline), within 6 hours of injury (acute), and at 7 days (subacute) postinjury. Differential gene expression was measured using the GeneChip 3' in vitro transcription Expression kit and Affymetrix microarrays, and genes with fold difference of 2 or more were identified using Partek. MAIN MEASURES: Whole genome differential gene expression, and cognitive and balance measures to asses for clinical symptoms pre- and postinjury. RESULTS: In the concussed athletes, we observed 67 downregulated and 4 upregulated genes in the acute period and 63 downregulated and 2 upregulated genes in the subacute period compared with baseline. Of these, there were 28 genes from both time points involved in the inflammatory response. No significant differences in gene expression were detected in the control group. CONCLUSIONS: Our findings suggest that recovery from sports-related concussion relates to modulation of inflammation through cytokine and chemokine gene pathways, which can contribute to future development of personalized therapeutic agents. Language: en