Young M. Lee

Predictors of postconcussion syndrome after sports-related concussion in young athletes: a matched case-control study

OBJECT Sport-related concussion (SRC) is a major public health problem. Approximately 90% of SRCs in high school athletes are transient; symptoms recover to baseline within 1 week. However, a small percentage of patients remain symptomatic several months after injury, with a condition known as postconcussion syndrome (PCS). The authors aimed to identify risk factors for PCS development in a cohort of exclusively young athletes (9-18 years of age) who sustained SRCs while playing a sport. METHODS The authors conducted a retrospective case-control study by using the Vanderbilt Sports Concussion Clinic database. They identified 40 patients with PCS and matched them by age at injury and sex to SRC control patients (1 PCS to 2 control). PCS patients were those experiencing persistent symptoms at 3 months after an SRC. Control patients were those with documented resolution of symptoms within 3 weeks of an SRC. Data were collected in 4 categories: 1) demographic variables; 2) key medical, psychiatric, and family history; 3) acute-phase postinjury symptoms (at 0-24 hours); and 4) subacute-phase postinjury features (at 0-3 weeks). The chi-square Fisher exact test was used to assess categorical variables, and the Mann-Whitney U-test was used to evaluate continuous variables. Forward stepwise regression models (Pin = 0.05, Pout = 0.10) were used to identify variables associated with PCS. RESULTS PCS patients were more likely than control patients to have a concussion history (p = 0.010), premorbid mood disorders (p = 0.002), other psychiatric illness (p = 0.039), or significant life stressors (p = 0.036). Other factors that increased the likelihood of PCS development were a family history of mood disorders, other psychiatric illness, and migraine. Development of PCS was not predicted by race, insurance status, body mass index, sport, helmet use, medication use, and type of symptom endorsement. A final logistic regression analysis of candidate variables showed PCS to be predicted by a history of concussion (OR 1.8, 95% CI 1.1-2.8, p = 0.016), preinjury mood disorders (OR 17.9, 95% CI 2.9-113.0, p = 0.002), family history of mood disorders (OR 3.1, 95% CI 1.1-8.5, p = 0.026), and delayed symptom onset (OR 20.7, 95% CI 3.2-132.0, p < 0.001). CONCLUSIONS In this age- and sex-matched case-control study of risk factors for PCS among youth with SRC, risk for development of PCS was higher in those with a personal and/or family history of mood disorders, other psychiatric illness, and migraine. These findings highlight the unique nature of SRC in youth. For this population, providers must recognize the value of establishing the baseline health and psychiatric status of children and their primary caregivers with regard to symptom reporting and recovery expectations. In addition, delayed symptom onset was an unexpected but strong risk factor for PCS in this cohort. Delayed symptoms could potentially result in late removal from play, rest, and care by qualified health care professionals. Taken together, these results may help practitioners identify young athletes with concussion who are at a greater danger for PCS and inform larger prospective studies for validation of risk factors from this cohort.

Catechol O-Methyltransferase Haplotype Predicts Immediate Musculoskeletal Neck Pain and Psychological Symptoms After Motor Vehicle Collision

UNLABELLED Genetic variations in the catechol-O-methyltransferase (COMT) gene have been associated with experimental pain and risk of chronic pain development, but no studies have examined genetic predictors of neck pain intensity and other patient characteristics after motor vehicle collision (MVC). We evaluated the association between COMT genotype and acute neck pain intensity and other patient characteristics in 89 Caucasian individuals presenting to the emergency department (ED) after MVC. In the ED in the hours after MVC, individuals with a COMT pain vulnerable genotype were more likely to report moderate-to-severe musculoskeletal neck pain (76 versus 41%, RR = 2.11 (1.33-3.37)), moderate or severe headache (61 versus 33%, RR = 3.15 (1.05-9.42)), and moderate or severe dizziness (26 versus 12%, RR = 1.97 (1.19-3.21)). Individuals with a pain vulnerable genotype also experienced more dissociative symptoms in the ED, and estimated a longer time to physical recovery (median 14 versus 7 days, P = .002) and emotional recovery (median 8.5 versus 7 days, P = .038). These findings suggest that genetic variations affecting stress response system function influence the somatic and psychological response to MVC, and provide the first evidence of genetic risk for clinical symptoms after MVC. PERSPECTIVE The association of COMT genotype with pain symptoms, psychological symptoms, and recovery beliefs exemplifies the pleiotropic effects of stress-related genes, which may provide the biological substrate for the biopsychosocial model of post-MVC pain. The identification of genes associated with post-MVC symptoms may also provide new insights into pathophysiology.

Recovery from sports-related concussion: Days to return to neurocognitive baseline in adolescents versus young adults

Background: Sports-related concussions (SRC) among high school and collegiate athletes represent a significant public health concern. The Concussion in Sport Group (CIS) recommended greater caution regarding return to play with children and adolescents. We hypothesized that younger athletes would take longer to return to neurocognitive baseline than older athletes after a SRC. Methods: Two hundred adolescent and young adult athletes who suffered a SRC were included in our clinical research cohort. Of the total participants, 100 were assigned to the 13-16 year age group and 100 to the 18-22 year age group and were matched on the number of prior concussions. Each participant completed baseline and postconcussion neurocognitive testing using the Immediate Post-Concussion assessment and Cognitive Testing (ImPACT) test battery. Return to baseline was defined operationally as post-concussion neurocognitive and symptom scores being equivalent to baseline using reliable change index (RCI) criteria. For each group, the average number of days to return to cognitive and symptom baseline were calculated. Independent sample t-tests were used to compare the mean number of days to return to baseline. Results: Significant differences were found for days to return to baseline between 13-16 year olds and 18-22 year olds in three out of four neurocognitive measures and on the total symptom score. The average number of days to return to baseline was greater for 13-16 year olds than for 18-22 year olds on the following variables: Verbal memory (7.2 vs. 4.7, P = 0.001), visual memory (7.1 vs. 4.7, P = 0.002), reaction time (7.2 vs. 5.1 P = 0.01), and postconcussion symptom scale (8.1 vs. 6.1, P = 0.026). In both groups, greater than 90% of athletes returned to neurocognitive and symptom baseline within 1 month. Conclusions: Our results in this clinical research study show that in SRC, athletes 13-16 years old take longer to return to their neurocognitive and symptom baselines than athletes 18-22 years old.

Pre‐Exposure of Human Adipose Mesenchymal Stem Cells to Soluble Factors Enhances Their Homing to Brain Cancer

Recent research advances have established mesenchymal stem cells (MSCs) as a promising vehicle for therapeutic delivery. Their intrinsic tropism for brain injury and brain tumors, their lack of immunogenicity, and their ability to breach the blood‐brain barrier make these cells an attractive potential treatment of brain disorders, including brain cancer. Despite these advantages, the efficiency of MSC homing to the brain has been limited in commonly used protocols, hindering the feasibility of such therapies. In the present study, we report a reproducible, comprehensive, cell culture‐based approach to enhance human adipose‐derived MSC (hAMSC) engraftment to brain tumors. We used micro‐ and nanotechnological tools to systematically model several steps in the putative homing process. By pre‐exposing hAMSCs to glioma‐conditioned media and the extracellular matrix proteins fibronectin and laminin, we achieved significant enhancements of the individual homing steps in vitro. This homing was confirmed in an in vivo rodent model of brain cancer. This comprehensive, cell‐conditioning approach provides a novel method to enhance stem cell homing to gliomas and, potentially, other neurological disorders.

Hypoxia-cultured human adipose-derived mesenchymal stem cells are non-oncogenic and have enhanced viability, motility, and tropism to brain cancer

Adult human adipose-derived mesenchymal stem cells (hAMSCs) are multipotent cells, which are abundant, easily collected, and bypass the ethical concerns that plague embryonic stem cells. Their utility and accessibility have led to the rapid development of clinical investigations to explore their autologous and allogeneic cellular-based regenerative potential, tissue preservation capabilities, anti-inflammatory properties, and anticancer properties, among others. hAMSCs are typically cultured under ambient conditions with 21% oxygen. However, physiologically, hAMSCs exist in an environment of much lower oxygen tension. Furthermore, hAMSCs cultured in standard conditions have shown limited proliferative and migratory capabilities, as well as limited viability. This study investigated the effects hypoxic culture conditions have on primary intraoperatively derived hAMSCs. hAMSCs cultured under hypoxia (hAMSCs-H) remained multipotent, capable of differentiation into osteogenic, chondrogenic, and adipogenic lineages. In addition, hAMSCs-H grew faster and exhibited less cell death. Furthermore, hAMSCs-H had greater motility than normoxia-cultured hAMSCs and exhibited greater homing ability to glioblastoma (GBM) derived from brain tumor-initiating cells from our patients in vitro and in vivo. Importantly, hAMSCs-H did not transform into tumor-associated fibroblasts in vitro and were not tumorigenic in vivo. Rather, hAMSCs-H promoted the differentiation of brain cancer cells in vitro and in vivo. These findings suggest an alternative culturing technique that can enhance the function of hAMSCs, which may be necessary for their use in the treatment of various pathologies including stroke, myocardial infarction, amyotrophic lateral sclerosis, and GBM.Adult human adipose-derived mesenchymal stem cells (hAMSCs) are multipotent cells, which are abundant, easily collected, and bypass the ethical concerns that plague embryonic stem cells. Their utility and accessibility have led to the rapid development of clinical investigations to explore their autologous and allogeneic cellular-based regenerative potential, tissue preservation capabilities, anti-inflammatory properties, and anticancer properties, among others. hAMSCs are typically cultured under ambient conditions with 21% oxygen. However, physiologically, hAMSCs exist in an environment of much lower oxygen tension. Furthermore, hAMSCs cultured in standard conditions have shown limited proliferative and migratory capabilities, as well as limited viability. This study investigated the effects hypoxic culture conditions have on primary intraoperatively derived hAMSCs. hAMSCs cultured under hypoxia (hAMSCs-H) remained multipotent, capable of differentiation into osteogenic, chondrogenic, and adipogenic lineages. In addition, hAMSCs-H grew faster and exhibited less cell death. Furthermore, hAMSCs-H had greater motility than normoxia-cultured hAMSCs and exhibited greater homing ability to glioblastoma (GBM) derived from brain tumor-initiating cells from our patients in vitro and in vivo. Importantly, hAMSCs-H did not transform into tumor-associated fibroblasts in vitro and were not tumorigenic in vivo. Rather, hAMSCs-H promoted the differentiation of brain cancer cells in vitro and in vivo. These findings suggest an alternative culturing technique that can enhance the function of hAMSCs, which may be necessary for their use in the treatment of various pathologies including stroke, myocardial infarction, amyotrophic lateral sclerosis, and GBM.

Does age affect symptom recovery after sports-related concussion? A study of high school and college athletes

OBJECT Sport-related concussions (SRCs) in high school and college athletes represent a significant public health concern. Research suggests that younger athletes fare worse symptomatically than older athletes after an SRC. Using reliable change index (RCI) methodology, the authors conducted a study to determine if there are age-related differences in number, severity, and resolution of postconcussion symptoms. METHODS Between 2009 and 2011, baseline measures of neurocognitive functions and symptoms in high school and college athletes were entered into a regional database. Seven hundred forty of these athletes later sustained an SRC. Ninety-two athletes in the 13- to 16-year-old group and 92 athletes in the 18- to 22-year-old group were matched for number of prior concussions, sex, biopsychosocial variables, and days to first postconcussion testing and symptom assessment. A nonparametric Mann-Whitney U-test was used to compare the severity of each of 22 symptoms comprising the Total Symptom Scale (TSS) at baseline and first postconcussion test. To obtain a family-wise p value of 0.05 for each test, the significance level for each symptom comparison was set at an alpha of 0.05/22 = 0.0023. The number of days to return to baseline TSS score was compared using the RCI methodology, set at the 80% confidence interval, equal to a change in raw score of 9.18 points on the TSS. RESULTS There was no statistically significant difference in symptom presence, symptom severity, and total symptoms between the age groups at baseline or at postconcussion testing. There was no statistically significant difference in return to baseline symptom scores between the age groups. CONCLUSIONS Using RCI methodology, there was no statistically significant difference between younger and older athletes in return to baseline symptoms postconcussion.

The prevalence and costs of defensive medicine among orthopaedic trauma surgeons: a national survey study.

Objectives: Defensive medicine includes medical practices that exonerate physicians from liability without benefit to patients. The national prevalence of defensive medicine in orthopaedic trauma surgery has not been investigated. Methods: In September 2010, 2000 orthopaedic surgeons randomly chosen from the American Academy of Orthopaedic Surgeons registry received invitations to answer a survey on defensive medicine. Among these surgeons, 1214 (61%) completed the survey and 222 (18.5%) identified themselves as nonmilitary orthopaedic traumatologists. Cost analysis was performed using Centers for Medicare and Medicaid data at the 2011 current procedural terminology code level and then aggregated to reflect the 8 domains of care assessed. Results: For orthopaedic traumatologists, on average 22% of all ordered tests were for defensive reasons (radiography, 19%; computed tomographic scanning, 23%; magnetic resonance imaging, 27%; ultrasound, 42%; referrals, 29%; laboratory tests, 23%; and biopsies, 16%). Defensive hospital admissions averaged 9% each month. Orthopaedic traumatologists reported fewer referrals to specialists compared with non-trauma orthopaedists (P = 0.02), with no significant difference in overall monthly defensive expenditures. Using 2011 current procedural terminology code reimbursement data, defensive medicine costs per respondent were calculated to be approximately

Awake Craniotomy vs Craniotomy Under General Anesthesia for Perirolandic Gliomas: Evaluating Perioperative Complications and Extent of Resection

7800 monthly or

The effects of American Society of Anesthesiologists physical status on length of stay and inpatient cost in the surgical treatment of isolated orthopaedic fractures.

94,000/y, which is 20% of each physicians spending. Given the approximately 2724 orthopaedic trauma surgeons in practice in the United States according to the 2010 American Academy of Orthopaedic Surgeons Census, the national cost of defensive medicine for orthopaedic trauma surgery is estimated to be

Pain and interference of pain with function and mood in elderly adults involved in a motor vehicle collision: a pilot study.

256.3 million annually. Conclusions: Defensive medicine among orthopaedic trauma surgeons is a significant factor in health care costs and of marginal benefit to patients. Policies aimed at managing liability risk may be useful in containing such practices. Level of Evidence: Economic Level IV. See Instructions for Authors for a complete description of levels of evidence.