Pamela M. Vacek

Ankle ligament injury risk factors: a prospective study of college athletes

Over two million individuals suffer ankle ligament trauma each year in the United States, more than half of these injuries are severe ligament sprains; however, very little is known about the factors that predispose individuals to these injuries. The purpose of this study was to determine the risk factors associated with ankle injury. We performed a prospective study of 118 Division I collegiate athletes who participated in soccer, lacrosse, or field hockey. Prior to the start of the athletic season, potential ankle injury risk factors were measured, subjects were monitored during the athletic season, and injuries documented. The number of ankle injuries per 1000 person‐days of exposure to sports was 1.6 for the men and 2.2 for the women. There were 13 injuries among the 68 women (19%) and seven injuries among the 50 men (13%), but these proportions were not significantly different. Women who played soccer had a higher incidence of ankle injury than those who played field hockey or lacrosse. Among men, there was no relationship between type of sport and incidence of injury. Factors associated with ankle ligament injury differ for men relative to women. Women with increased tibial varum and calcaneal eversion range of motion are at greater risk of suffering ankle ligament trauma, while men with increased talar tilt are at greater risk. Generalized joint laxity, strength, postural stability, and muscle reaction time were unrelated to injury.

NF-κB Activation in Airways Modulates Allergic Inflammation but Not Hyperresponsiveness

Airways display robust NF-κB activation and represent targets for anti-inflammatory asthma therapies, but the functional importance of NF-κB activation in airway epithelium remains enigmatic. Therefore, transgenic mice were created in which NF-κB activation is repressed specifically in airways (CC10-IκBαSR mice). In response to inhaled Ag, transgenic mice demonstrated significantly ameliorated inflammation, reduced levels of chemokines, T cell cytokines, mucus cell metaplasia, and circulating IgE compared with littermate controls. Despite these findings, Ag-driven airways hyperresponsiveness was not attenuated in CC10-IκBαSR mice. This study clearly demonstrates that airway epithelial NF-κB activation orchestrates Ag-induced inflammation and subsequent adaptive immune responses, but does not contribute to airways hyperresponsiveness, the cardinal feature that underlies asthma.

Breast Cancer Risk by Breast Density, Menopause, and Postmenopausal Hormone Therapy Use

PURPOSE We determined whether the association between breast density and breast cancer risk and cancer severity differs according to menopausal status and postmenopausal hormone therapy (HT) use. METHODS We collected data on 587,369 women who underwent 1,349,027 screening mammography examinations; 14,090 women were diagnosed with breast cancer. We calculated 5-year breast cancer risk from a survival model for subgroups of women classified by their Breast Imaging Reporting and Data System (BIRADS) breast density, age, menopausal status, and current HT use, assuming a body mass index of 25 kg/m(2). Odds of advanced (ie, IIb, III, IV) versus early (ie, I, IIa) stage invasive cancer was calculated according to BIRADS density. RESULTS Breast cancer risk was low among women with low density (BIRADS-1): women age 55 to 59 years, 5-year risk was 0.8% (95% CI, 0.6 to 0.9%) for non-HT users and 0.9% (95% CI, 0.7% to 1.1%) for estrogen and estrogen plus progestin users. Breast cancer risk was high among women with very high density (BIRADS-4), particularly estrogen plus progestin users: women age 55 to 59 years, 5-year risk was 2.4% (95% CI, 2.0% to 2.8%) for non-HT users, 3.0% (95% CI, 2.6% to 3.5%) for estrogen users, and 4.2% (95% CI, 3.7% to 4.6%) for estrogen plus progestin users. Advanced-stage breast cancer risk was increased 1.7-fold for postmenopausal HT users who had very high density (BIRADS-4) compared to those with average density (BIRADS-2). CONCLUSION Postmenopausal women with high breast density are at increased risk of breast cancer and should be aware of the added risk of taking HT, especially estrogen plus progestin.

Intoxication and injury

The relationship between alcohol use and injury severity was investigated in trauma patients admitted to a tertiary referral hospital during a 23-month period. Admission blood alcohol levels (BALs) were obtained on 427 trauma patients, who were stratified into three groups: those with no measurable blood alcohol, those within the legal limit of 100 mg/dL, and those over the legal limit or intoxicated. The no-alcohol group had significantly lower injury severity than the other two groups (p less than 0.001). Even when the BAL was well within the legal limit, injuries suffered by those in the alcohol-positive groups were more severe than those in the no-alcohol group. Confirmatory evidence of the effect of alcohol on injury severity was reflected by a 2.3% mortality in alcohol-negative patients compared with a 13.3% death rate in alcohol-positive patients (p less than 0.0001). To assess the potentially confounding effect of alcohol on injury scoring accuracy, we examined the change in Glasgow Coma Scale (GCS) scores following admission. No significant differences were found when admission GCS values were compared with GCS determinations made 24 hours following admission by separate observers. To correct for any potential bias as a tertiary referral center, repeat analysis with exclusion of transferred patients was done with essentially no change in results. Our data revealed a highly significant relationship between alcohol use, degree of injury, and resource consumption.

A Prospective Evaluation of the Landing Error Scoring System (LESS) as a Screening Tool for Anterior Cruciate Ligament Injury Risk

Background: Anterior cruciate ligament (ACL) injuries are immediately disabling, costly, take a significant amount of time to rehabilitate, and are associated with an increased risk of developing posttraumatic osteoarthritis of the knee. Specific multiplanar movement patterns of the lower extremity, such as those associated with the drop vertical jump (DVJ) test, have been shown to be associated with an increased risk of suffering noncontact ACL injuries. The Landing Error Scoring System (LESS) has been developed as a tool that can be applied to identify individuals who display at-risk movement patterns during the DVJ. Hypothesis: An increase in LESS score is associated with an increased risk of noncontact ACL injury. Study Design: Case-control study; Level of evidence, 3. Methods: Over a 3-year interval, 5047 high school and college participants performed preseason DVJ tests that were recorded using commercial video cameras. All participants were followed for ACL injury during their sports season, and video data from injured participants and matched controls were then assessed with the LESS. Conditional logistic regression analysis was used to examine the association between LESS score and ACL injury risk in all participants as well as subgroups of female, male, high school, and college participants. Results: There was no relationship between the risk of suffering ACL injury and LESS score whether measured as a continuous or a categorical variable. This was the case for all participants combined (odds ratio, 1.04 per unit increase in LESS score; 95% confidence interval, 0.80-1.35) as well as within each subgroup (odds ratio range, 0.99-1.14). Conclusion: The LESS did not predict ACL injury in our cohort of high school and college athletes.

The Relationship Between Menstrual Cycle Phase and Anterior Cruciate Ligament Injury A Case-Control Study of Recreational Alpine Skiers

Background Female athletes suffer a greater incidence of anterior cruciate ligament tears compared with male athletes when participating in common sports; however, very little is known about the factors that explain this disparity. Study Design Case-control study; Level of evidence, 3. Methods Female recreational alpine skiers with an anterior cruciate ligament rupture and age-matched control skiers provided a serum sample and self-reported menstrual history data immediately after injury. Both serum concentrations of progesterone and menstrual history were then used to group subjects into either preovulatory or postovulatory phases of the menstrual cycle. Results Analysis of serum concentrations of progesterone revealed that alpine skiers in the preovulatory phase of the menstrual cycle were significantly more likely to tear their anterior cruciate ligaments than were skiers in the postovulatory phase (odds ratio, 3.22; 95% confidence interval, 1.09-9.52; P = .027). Analysis of menstrual history data found similar results, but the difference was not statistically significant (odds ratio, 2.38; 95% confidence interval, 0.86-6.54; P = .086). Conclusion The likelihood of sustaining an anterior cruciate ligament injury does not remain constant during the menstrual cycle; instead, the risk of suffering an anterior cruciate ligament disruption is significantly greater during the preovulatory phase of the menstrual cycle compared with the postovulatory phase. Clinical Relevance Phase of menstrual cycle may be one of the risk factors that influence knee ligament injury among female alpine skiers. The findings from this study should be considered in subsequent studies designed to identify persons at risk for anterior cruciate ligament injury and to develop intervention strategies.

Crocidolite asbestos and SV40 are cocarcinogens in human mesothelial cells and in causing mesothelioma in hamsters.

Only a fraction of subjects exposed to asbestos develop malignant mesothelioma (MM), suggesting that additional factors may render some individuals more susceptible. We tested the hypothesis that asbestos and Simian virus (SV40) are cocarcinogens. Asbestos and SV40 in combination had a costimulatory effect in inducing ERK1/2 phosphorylation and activator protein-1 (AP-1) activity in both primary Syrian hamster mesothelial cells (SHM) and primary human mesothelial cells (HM). Ap-1 activity caused the expression and activation of matrix metalloprotease (MMP)-1 and MMP-9, which in turn led to cell invasion. Experiments using siRNA and chemical inhibitors confirmed the specificity of these results. The same effects were observed in HM and SHM. Experiments in hamsters showed strong cocarcinogenesis between asbestos and SV40: SV40 did not cause MM, asbestos caused MM in 20% of hamsters, and asbestos and SV40 together caused MM in 90% of hamsters. Significantly lower amounts of asbestos were sufficient to cause MM in animals infected with SV40. Our results indicate that mineral fibers and viruses can be cocarcinogens and suggest that lower amounts of asbestos may be sufficient to cause MM in individuals infected with SV40.

Risk Factors for Anterior Cruciate Ligament Injury: A Review of the Literature — Part 1: Neuromuscular and Anatomic Risk

Context: Injuries to the anterior cruciate ligament (ACL) of the knee are immediately debilitating and can cause long-term consequences, including the early onset of osteoarthritis. It is important to have a comprehensive understanding of all possible risk factors for ACL injury to identify individuals who are at risk for future injuries and to provide an appropriate level of counseling and programs for prevention. Objective: This review, part 1 of a 2-part series, highlights what is known and still unknown regarding anatomic and neuromuscular risk factors for injury to the ACL from the current peer-reviewed literature. Data Sources: Studies were identified from MEDLINE (1951–March 2011) using the MeSH terms anterior cruciate ligament, knee injury, and risk factors. The bibliographies of relevant articles and reviews were cross-referenced to complete the search. Study Selection: Prognostic studies that utilized the case-control and prospective cohort study designs to evaluate risk factors for ACL injury were included in this review. Results: A total of 50 case-control and prospective cohort articles were included in the review, and 30 of these studies focused on neuromuscular and anatomic risk factors. Conclusions: Several anatomic and neuromuscular risk factors are associated with increased risk of suffering ACL injury—such as female sex and specific measures of bony geometry of the knee joint, including decreased intercondylar femoral notch size, decreased depth of concavity of the medial tibial plateau, increased slope of the tibial plateaus, and increased anterior-posterior knee laxity. These risk factors most likely act in combination to influence the risk of ACL injury; however, multivariate risk models that consider all the aforementioned risk factors in combination have not been established to explore this interaction.

Determination of hprt mutant frequencies in T-lymphocytes from a healthy pediatric population: statistical comparison between newborn, children and adult mutant frequencies, cloning efficiency and age

Somatic cell mutant frequencies at the hprt locus of the X-chromosome were measured with the T-lymphocyte cloning assay in a healthy pediatric population. Assays were performed on 49 subjects (29 males and 20 females) ranging in age from 0.08 to 15.2 years. A statistical analysis of the thioguanine-resistant (TGr) mutant frequency (MF), unselected cloning efficiency (CE) and age was performed using data obtained in this study and those previously obtained in our laboratory on 66 newborn umbilical cord blood samples and 230 adult blood samples. For statistical comparisons pediatric subjects were divided into 4 groups. Group I included cord blood samples (age 0 years); Group II were subjects between 0 and 5 years; Group III were between 6 and 11 years and Group IV were between 12 and 17 years. The ln MF of Groups I and II were significantly lower than Groups III and IV (p < 0.05). The mean ln MF for each of Groups I-IV was significantly lower than the adult value. The cloning efficiency for Group I was significantly lower than that for Groups II-IV and adults. The relationships among the ln MF, unselected CE and age were expressed by the equations: ln (MF) = 0.945 -2.453 CE (p < 0.001) and ln (MF) = 0.114 + 0.063 age (p 0.004). The slope coefficients for unselected CE and age were significantly different from adults (p < 0.05). Regression analysis of combined data from Groups I-IV and adults were performed using both age and unselected CE as well as terms to reflect differences in their relationships with ln MF in adults and children. The results showed that the intercept and the age coefficients differ significantly for children and adults after adjustment for CE and yielded the following equations: ln (MF) = 0.548 -1.676 CE + 0.075 age, (Groups I-IV) and ln (MF) = 2.263 -1.676 CE + 0.014 age (adults). An alternative statistical model using ln (age ), ln (MF) = 0.381 -1.767 CE + 0.673 ln (age + 1), (p < 0.001), describes the rapid increase in MF with age that levels off in late adolescence. These findings demonstrate the changing influence of age on mutant frequency in the pediatric population as compared to the adult populations. These studies also illustrate that the increase in background somatic mutant frequencies at the hprt locus in T-lymphocytes is not linear from birth to adolescence and is significantly different from that seen in the adult population.(ABSTRACT TRUNCATED AT 400 WORDS)

Relationship Between Mammographic Density and Breast Cancer Death in the Breast Cancer Surveillance Consortium

BACKGROUND Women with elevated mammographic density have an increased risk of developing breast cancer. However, among women diagnosed with breast cancer, it is unclear whether higher density portends reduced survival, independent of other factors. METHODS We evaluated relationships between mammographic density and risk of death from breast cancer and all causes within the US Breast Cancer Surveillance Consortium. We studied 9232 women diagnosed with primary invasive breast carcinoma during 1996-2005, with a mean follow-up of 6.6 years. Mammographic density was assessed using the Breast Imaging Reporting and Data System (BI-RADS) density classification. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated by Cox proportional hazards regression; women with scattered fibroglandular densities (BI-RADS 2) were the referent group. All statistical tests were two-sided. RESULTS A total of 1795 women died, of whom 889 died of breast cancer. In multivariable analyses (adjusted for site, age at and year of diagnosis, American Joint Committee on Cancer stage, body mass index, mode of detection, treatment, and income), high density (BI-RADS 4) was not related to risk of death from breast cancer (HR = 0.92, 95% CI = 0.71 to 1.19) or death from all causes (HR = 0.83, 95% CI = 0.68 to 1.02). Analyses stratified by stage and other prognostic factors yielded similar results, except for an increased risk of breast cancer death among women with low density (BI-RADS 1) who were either obese (HR = 2.02, 95% CI = 1.37 to 2.97) or had tumors of at least 2.0 cm (HR = 1.55, 95% CI = 1.14 to 2.09). CONCLUSIONS High mammographic breast density was not associated with risk of death from breast cancer or death from any cause after accounting for other patient and tumor characteristics. Thus, risk factors for the development of breast cancer may not necessarily be the same as factors influencing the risk of death after breast cancer has developed.