Sport Type and Risk of Subsequent Injury in Collegiate Athletes Following Concussion: a LIMBIC MATARS Consortium Investigation.

OBJECTIVE: To investigate the association between sport type (collision, contact, non-contact) and subsequent injury risk following concussion in collegiate athletes. MATERIALS AND METHODS: This retrospective chart review of 248 collegiate athletes with diagnosed concussions (age: 20.0 ± 1.4 years; height: 179.6 ± 10.9 cm; mass: 79.0 ± 13.6 kg, 63% male) from NCAA athletic programs (n = 11) occurred between the 2015-2020 athletic seasons. Acute injuries that occurred within six months following concussion were evaluated. Subsequent injuries were grouped by lower extremity, upper extremity, trunk, or concussion. The independent variable was sport type: collision, contact, non-contact. A Cox proportional hazard model was used to assess the risk of subsequent injury between sport types. RESULTS: Approximately 28% (70/248) of athletes sustained a subsequent acute injury within six months post-concussion. Collision sport athletes had a significantly higher risk of sustaining any injury (HR: 0.41, p < 0.001, 95% CI: 0.28, 0.62), lower extremity (HR: 0.55, p = 0.04, 95% CI: 0.32, 0.97), and upper extremity (HR: 0.41, p = 0.01, 95% CI: 0.20, 0.81) injuries following concussion. No differences between sport types were observed for other injuries. CONCLUSION: Collision sport athletes had a higher rate of any subsequent injury, lower, and upper extremity injuries following concussion. Future research should focus on sport-specific secondary injury prevention efforts.

Concussion diagnosis and recovery in relation to collegiate athletic department classification: a LIMBIC MATARS consortium investigation.

PURPOSE: We investigated time to reach concussion diagnosis and recovery milestones in collegiate athletes relative to their schools' National Collegiate Athletic Association (NCAA) classification. METHODS: We retrospectively examined 849 (43.1% female) concussion cases from 11 NCAA institutions (Division I Power 5 [n = 4], Division I Non-Power 5 [n = 4], and Division II/III [n = 3]) from the 2015-16 to 2019-20 athletic seasons. Our primary outcome measures were days to reach specific clinical milestones following concussion. RESULTS: Median (IQR) time from injury to diagnosis was significantly longer at Division II/III institutions (1 [0-4] days) compared to Division I Power 5 (0 [0-1] days) and Division I Non-Power 5 (0 [0-1] days) institutions (p < 0.001). Likewise, Division II/III athletes (15 [11-22] days) took significantly longer to return to sport after concussion than Division I Power 5 (10 [7-16] days) and Division I Non-Power 5 (11 [7-18.5] days) athletes (p < 0.001). CONCLUSION: Division II/III athletes had delayed concussion diagnoses and return to sport timelines compared to Division I athletes. Our results suggest that differences in sports medicine resources across NCAA divisions may influence injury recognition and recovery in collegiate athletes with concussion.

Physical activity and recovery following concussion in collegiate athletes: a LIMBIC MATARS Consortium Investigation.

OBJECTIVE: To investigate whether routine daily activities (RDA), non-prescribed exercise (Non-ERx), or prescribed exercise (ERx) were associated with recovery from sport-related concussion (SRC) in collegiate athletes. MATERIALS AND METHODS: Data for this cross-sectional, retrospective chart review of collegiate athletes diagnosed with SRC (n = 285[39.6% female], age = 19.5 ± 1.4 years) were collected during the 2015-16 to 2019-20 athletic seasons. The independent variable was group (RDA, Non-ERx, ERx). Dependent variables included days from date of diagnosis to symptom resolution (Dx-SR) and SR to return to sport (SR-RTS). RESULTS: Those in the Non-ERx group took nearly 1.3 times longer to achieve SR (IRR = 1.28, 95% CI: 1.11, 1.46) and, 1.8 times longer for RTS (IRR = 1.82, 95% CI: 1.11, 2.71) when compared to those in the RDA group. No other comparisons were significant. CONCLUSION: Collegiate athletes in the Non-ERx group took approximately 1 week longer to achieve SR as compared to the RDA and ERx groups. Our findings suggest that if exercise is recommended following SRC, it must be clearly and specifically prescribed. If exercise parameters cannot be prescribed, or monitored, RDA appear to be similarly beneficial during recovery for collegiate athletes with concussion.

Salivary microRNA as a prospective tool for concussion diagnosis and management: A scoping review.

BACKGROUND: Despite increased efforts directed toward research, concussions are a growing concern and can be a complex injury for healthcare professionals to manage. Current practices are largely dependent on patients self-reporting symptoms and a clinical assessment, which uses objective tools that lack effectiveness. With the demonstrated effects of concussions, it is imperative that a more valid or reliable objective tool, like a clinical biomarker, be identified to improve outcomes. One potential biomarker that has shown promise is salivary microRNA. However, there is no objective consensus as to which microRNA offers the most clinical value regarding concussions, hence this review. Therefore, the purpose of this scoping review was to identify salivary miRNAs associated with concussions. METHODS: Two independent reviewers performed a literature search to identify research articles. Studies using human subjects, collected salivary miRNA, and were published in English were included. Data of interest were salivary miRNA, collection timing, and relation to concussion diagnosis or management. RESULTS: This paper reviews nine studies that analyzed salivary miRNA for concussion diagnosis and management. CONCLUSIONS: In total, the studies have identified 49 salivary miRNA that show promise in assisting with concussion practices. With continued research, the use of salivary miRNA may enhance clinicians' abilities to diagnose and manage concussions.

Refinement of saliva microRNA biomarkers for sports-related concussion.

BACKGROUND: Recognizing sport-related concussion (SRC) is challenging and relies heavily on subjective symptom reports. An objective, biological marker could improve recognition and understanding of SRC. There is emerging evidence that salivary micro-ribonucleic acids (miRNAs) may serve as biomarkers of concussion; however, it remains unclear whether concussion-related miRNAs are impacted by exercise. We sought to determine whether 40 miRNAs previously implicated in concussion pathophysiology were affected by participation in a variety of contact and non-contact sports. Our goal was to refine a miRNA-based tool capable of identifying athletes with SRC without the confounding effects of exercise. METHODS: This case-control study harmonized data from concussed and non-concussed athletes recruited across 10 sites. Levels of salivary miRNAs within 455 samples from 314 individuals were measured with RNA sequencing. Within-subjects testing was used to identify and exclude miRNAs that changed with either (a) a single episode of exercise (166 samples from 83 individuals) or (b) season-long participation in contact sports (212 samples from 106 individuals). The miRNAs that were not impacted by exercise were interrogated for SRC diagnostic utility using logistic regression (172 samples from 75 concussed and 97 non-concussed individuals). RESULTS: Two miRNAs (miR-532-5p and miR-182-5p) decreased (adjusted p < 0.05) after a single episode of exercise, and 1 miRNA (miR-4510) increased only after contact sports participation. Twenty-three miRNAs changed at the end of a contact sports season. Two of these miRNAs (miR-26b-3p and miR-29c-3p) were associated (R > 0.50; adjusted p < 0.05) with the number of head impacts sustained in a single football practice. Among the 15 miRNAs not confounded by exercise or season-long contact sports participation, 11 demonstrated a significant difference (adjusted p < 0.05) between concussed and non-concussed participants, and 6 displayed moderate ability (area under curve > 0.70) to identify concussion. A single ratio (miR-27a-5p/miR-30a-3p) displayed the highest accuracy (AUC = 0.810, sensitivity = 82.4%, specificity = 73.3%) for differentiating concussed and non-concussed participants. Accuracy did not differ between participants with SRC and non-SRC (z = 0.5, p = 0.60). CONCLUSION: Salivary miRNA levels may accurately identify SRC when not confounded by exercise. Refinement of this approach in a large cohort of athletes could eventually lead to a non-invasive, sideline adjunct for SRC assessment.

Diagnosing mild traumatic brain injury using saliva RNA compared to cognitive and balance testing.

BACKGROUND: Early, accurate diagnosis of mild traumatic brain injury (mTBI) can improve clinical outcomes for patients, but mTBI remains difficult to diagnose because of reliance on subjective symptom reports. An objective biomarker could increase diagnostic accuracy and improve clinical outcomes. The aim of this study was to assess the ability of salivary noncoding RNA (ncRNA) to serve as a diagnostic adjunct to current clinical tools. We hypothesized that saliva ncRNA levels would demonstrate comparable accuracy for identifying mTBI as measures of symptom burden, neurocognition, and balance. METHODS: This case-control study involved 538 individuals. Participants included 251 individuals with mTBI, enrolled ≤14 days postinjury, from 11 clinical sites. Saliva samples (n = 679) were collected at five time points (≤3, 4-7, 8-14, 15-30, and 31-60 days post-mTBI). Levels of ncRNAs (microRNAs, small nucleolar RNAs, and piwi-interacting RNAs) were quantified within each sample using RNA sequencing. The first sample from each mTBI participant was compared to saliva samples from 287 controls. Samples were divided into testing (n = 430; mTBI = 201 and control = 239) and training sets (n = 108; mTBI = 50 and control = 58). The test set was used to identify ncRNA diagnostic candidates and create a diagnostic model. Model accuracy was assessed in the naïve test set. RESULTS: A model utilizing seven ncRNA ratios, along with participant age and chronic headache status, differentiated mTBI and control participants with a cross-validated area under the curve (AUC) of .857 in the training set (95% CI, .816-.903) and .823 in the naïve test set. In a subset of participants (n = 321; mTBI = 176 and control = 145) assessed for symptom burden (Post-Concussion Symptom Scale), as well as neurocognition and balance (ClearEdge System), these clinical measures yielded cross-validated AUC of .835 (95% CI, .782-.880) and .853 (95% CI, .803-.899), respectively. A model employing symptom burden and four neurocognitive measures identified mTBI participants with similar AUC (.888; CI, .845-.925) as symptom burden and four ncRNAs (.932; 95% CI, .890-.965). CONCLUSION: Salivary ncRNA levels represent a noninvasive, biologic measure that can aid objective, accurate diagnosis of mTBI.

Saliva microRNA Biomarkers of Cumulative Concussion.

Recurrent concussions increase risk for persistent post-concussion symptoms, and may lead to chronic neurocognitive deficits. Little is known about the molecular pathways that contribute to persistent concussion symptoms. We hypothesized that salivary measurement of microribonucleic acids (miRNAs), a class of epitranscriptional molecules implicated in concussion pathophysiology, would provide insights about the molecular cascade resulting from recurrent concussions. This hypothesis was tested in a case-control study involving 13 former professional football athletes with a history of recurrent concussion, and 18 age/sex-matched peers. Molecules of interest were further validated in a cross-sectional study of 310 younger individuals with a history of no concussion (n = 230), a single concussion (n = 56), or recurrent concussions (n = 24). There was no difference in neurocognitive performance between the former professional athletes and their peers, or among younger individuals with varying concussion exposures. However, younger individuals without prior concussion outperformed peers with prior concussion on three balance assessments. Twenty salivary miRNAs differed (adj. p < 0.05) between former professional athletes and their peers. Two of these (miR-28-3p and miR-339-3p) demonstrated relationships (p < 0.05) with the number of prior concussions reported by younger individuals. miR-28-3p and miR-339-5p may play a role in the pathophysiologic mechanism involved in cumulative concussion effects.