Faculty Bibliography

Introduction and Objectives: Lymphedema is an incurable and disfiguring disease secondary to excessive fluid and protein in the interstitium as a result of lymphatic obstruction. Pneumatic compression (PC) offers a novel modality for treatment of lymphatic obstruction through targeting lymphatic beds and mimicking a functional drainage system. The objective of this study is to demonstrate improved quality of life in patients with lower extremity lymphedema. Methods: Consecutive patients presenting to a single institution for treatment of lymphedema were all treated with PC for at least three months. All patients underwent a pre-and post-PC assessment of episodes of cellulitis, number of ulcers, and venous insufficiency. Post-PC symptom questionnaires were administered. Symptom improvement was the primary outcome for analysis. Results: 100 patients met inclusion criteria. At presentation, 70 % were female with a mean age of 57.5 years. Secondary lymphedema was present in 78%. Mean length of PC use was 12.7 months with a mean of 5.3 treatments per week. The number of episodes of cellulitis and ulcers pre- and post-PC decreased from mean of 0.26 to 0.05 episodes (p=0.002) and 0.12 to 0.02 ulcers (p=0.007) respectively. 14 % had concomitant superficial venous insufficiency, all of whom underwent venous ablation. 100% of patients reported symptomatic improvement post-PC with 54% greatly improved. 90% would recommend the treatment to others. Conclusions: PC improves symptom relief and reduces episodes of cellulitis and ulceration in lower extremity lymphedema. It is well tolerated by patients and should be recommended as an adjunct to standard lymphedema therapy. Screening for venous insufficiency is recommended

BACKGROUND: Cannabis (marijuana) use and acceptance towards use are increasing in the US, and state-level policies are becoming more liberal. A wealth of research has been conducted to examine risk factors for use; however, studies rarely differentiate between different forms of marijuana. OBJECTIVE: We sought to determine prevalence of use and delineate who is at risk for use of hashish, a more potent form of marijuana. METHODS: We examined data from a nationally representative sample of high school seniors in the Monitoring the Future study (2007-2011; weighted n = 10 597). We determined how sociodemographic factors and reasons for marijuana use correlated with recent (12 month) hashish use. RESULTS: Prevalence of recent hashish use was 6.5% and it was used by 18.3% of recent marijuana users. Hashish and other marijuana use tended to share many of the same correlates; however, associations were often stronger for hashish use. Females were consistently at low risk for use and users of other drugs were consistently at high risk for use. Black students tended to be at low risk for hashish use. Low risk of identifying as Hispanic or religious and high risk of higher personal income or going out more evenings per week for fun disappeared when controlling for other drug use. Using marijuana because the student felt he/she was "hooked" nearly doubled the odds for hashish use. CONCLUSIONS: This was the first national study to examine prevalence and correlates of hashish use. These findings can inform prevention in a time of increasing popularity of marijuana use.

BACKGROUND: Previous studies indicate that breast milk arsenic concentrations are relatively low even in areas with high drinking water arsenic. However, it is uncertain whether breastfeeding leads to reduced infant exposure to arsenic in regions with lower arsenic concentrations. OBJECTIVE: We estimated the relative contributions of breast milk and formula to arsenic exposure during early infancy in a U.S. population. METHODS: We measured arsenic in home tap water (n=874), urine from six-week-old infants (n=72), and breast milk from mothers (n=9) enrolled in the New Hampshire Birth Cohort Study (NHBCS) using inductively coupled plasma mass spectrometry. Using data from a three-day food diary, we compared urinary arsenic across infant feeding types and developed predictive exposure models to estimate daily arsenic intake from breast milk and formula. RESULTS: Urinary arsenic concentrations were generally low (median 0.17 microg/L, maximum 3.0 microg/L) but 7.5 times higher for infants fed exclusively with formula than for infants fed exclusively with breast milk (beta = 2.02; 95% CI: 1.21, 2.83; P<0.0001, adjusted for specific gravity). Similarly, the median estimated daily arsenic intake by NHBCS infants was 5.5 times higher for formula-fed infants (0.04 microg/kg/d) compared to breastfed infants (0.22 microg/kg/d). Given median arsenic concentrations measured in NHBCS tap water and previously published for formula powder, formula powder was estimated to account for ~70% of median exposure among formula-fed NHBCS infants. CONCLUSIONS: Our findings suggest that breastfed infants have lower arsenic exposure than formula-fed infants, and that both formula powder and drinking water can be sources of exposure for U.S. infants.

Background: Mild traumatic brain injuries are frequently evaluated in EDs. Standardized concussion surveillance tools such as the SCAT 3 have been proposed. Developed as a post-injury tool for athletes, SCAT3 is routinely used in pre-injury, baseline assessment. Population-based normative data can aid in interpretation of individual variability or when baseline data are unavailable. To date, all SCAT3 data have been collected in the athlete population with an absence of data on non-athlete (N-A) controls or acutely injured nonathletes. Objectives: We investigate SCAT3 subcomponents in N-A healthy controls, corpus (non head-injured) trauma, and acutely head-injured patients presenting to the ED to derive reference values for novel populations. We hypothesize that trauma patients with suspected head injury will have worse SCAT3 metrics than uninjured controls. Methods: Target groups were extracted from a database of prospectively recruited patients. SCAT3/SAC (Standardized Assessment of Concussion) was administered at time of ED presentation or recruitment. Multi-sample comparisons were evaluated by the Kruskal- Wallis test; pairwise comparisons were analyzed by the Steel-Dwass procedure. Results: A comparison of SCAT3 subcomponents by patient group is seen in Table 732a. One hundred eleven N-A healthy controls, 121 bodily trauma not warranting head CT in ED, 242 head trauma with negative head CT findings, and 67 head trauma patients with positive head CT were evaluated. Control group comparison seen in Table 732b. In number of symptoms, symptom severity score, and SAC, there was a significant difference between control, corpus and - CT/+CT groups. In immediate memory and Balance Error Scoring System (BESS), there was a significant difference between control, corpus, and -CT/+CT, with corpus statistically similar to -CT/ +CT. In concentration, there was a significant difference between control, corpus, and -CT/+CT, with corpus similar to -CT. In orientation, there was a significant difference between control/corpus and -CT/+CT. Conclusion: In healthy, N-A controls, all SCAT3 values were significantly different from all trauma groups'. In -CT/+CT groups, all SCAT3 values were similar to each other. A graded effect was seen from control to corpus to head trauma. Diagnostic ranges of SCAT3 subcomponents vary in the N-A and bodily trauma population. (Table presented)

Because we previously identified high rates of past TBI among adolescents arriving in the New York City (NYC) jail system we engaged adolescents in nine TBI focus groups to characterize better the level of understanding regarding the relationship between TBI and violence. During these groups, the following themes emerged: 1) physical and psychological impacts of violence; 2) roots of violence; 3) the use of violence as capital in the face of a marginalized social status; and 4) the inevitability of violence, particularly in a jail setting. Although these focus groups were initiated as a means to engage adolescents around the clinical problem of TBI, their observations are strongly centered in the larger context of violence. These results suggest that intervening in the problem of TBI among our patients will require broad-based changes in the environmental and interpersonal realities, both in the jail setting, and the communities where these adolescents reside.

BACKGROUND:Transcriptomic studies hold great potential towards understanding the human aging process. Previous transcriptomic studies have identified many genes with age-associated expression levels; however, small samples sizes and mixed cell types often make these results difficult to interpret. RESULTS:Using transcriptomic profiles in CD14+ monocytes from 1,264 participants of the Multi-Ethnic Study of Atherosclerosis (aged 55-94 years), we identified 2,704 genes differentially expressed with chronological age (false discovery rate, FDR ≤ 0.001). We further identified six networks of co-expressed genes that included prominent genes from three pathways: protein synthesis (particularly mitochondrial ribosomal genes), oxidative phosphorylation, and autophagy, with expression patterns suggesting these pathways decline with age. Expression of several chromatin remodeler and transcriptional modifier genes strongly correlated with expression of oxidative phosphorylation and ribosomal protein synthesis genes. 17% of genes with age-associated expression harbored CpG sites whose degree of methylation significantly mediated the relationship between age and gene expression (p < 0.05). Lastly, 15 genes with age-associated expression were also associated (FDR ≤ 0.01) with pulse pressure independent of chronological age. Comparing transcriptomic profiles of CD14+ monocytes to CD4+ T cells from a subset (n = 423) of the population, we identified 30 age-associated (FDR < 0.01) genes in common, while larger sets of differentially expressed genes were unique to either T cells (188 genes) or monocytes (383 genes). At the pathway level, a decline in ribosomal protein synthesis machinery gene expression with age was detectable in both cell types. CONCLUSIONS:An overall decline in expression of ribosomal protein synthesis genes with age was detected in CD14+ monocytes and CD4+ T cells, demonstrating that some patterns of aging are likely shared between different cell types. Our findings also support cell-specific effects of age on gene expression, illustrating the importance of using purified cell samples for future transcriptomic studies. Longitudinal work is required to establish the relationship between identified age-associated genes/pathways and aging-related diseases.

BACKGROUND: Treatment options for neuromyelitis optica (NMO) are currently based on small retrospective case series and open label studies, ranging from 10 to 103 patients. OBJECTIVE: To compare the efficacy and tolerability of azathioprine, cyclophosphamide, mycophenolate, and rituximab in patients with neuromyelitis optica. METHODS: This is a retrospective chart review and telephone follow-up study of 71 patients with NMO or NMO spectrum disorder, 54 of whom were treated with the study drugs. We compared adverse events, annualized relapse rates and expanded disability status scales before and after treatment. RESULTS: The median ARR decreased from 1.17 to 0.25 on rituximab (P<0.01), 0.92 to 0.56 on azathioprine (P=0.475), 1.06 to 0.39 on mycophenolate (P<0.05) and 1.30 to 0.92 on cyclophosphamide (P=0.746). When compared directly to azathioprine, rituximab significantly reduced relapse rates (P=0.021). The median EDSS decreased from 7 to 5 on rituximab (P<0.01) and 7 to 6 on azathioprine (P<0.01), and did not change significantly on mycophenolate (4 to 5; P=0.463) or cyclophosphamide (6.5 to 6.5; P=0.881). Twenty-five percent of patients noted adverse events on rituximab, 36% on azathioprine, 36% on mycophenolate, and 80% on cyclophosphamide. CONCLUSION: Rituximab significantly reduces relapse rates and improves disability while maintaining comparable tolerability to other immunosuppressive treatments for NMO.

Introduction: Disconjugate eye movements have been associated with traumatic brain injury since ancient times. Ocular motility dysfunction may be present in up to 90% of patients with concussion or blast injury. Methods: We developed an algorithm for eye tracking in which the Cartesian coordinates of the right and left pupils are tracked over 200 seconds and compared to each other as a subject watches a short film clip moving inside an aperture on a computer screen. We prospectively eye tracked 64 normal healthy non-injured control subjects and compared findings to 75 trauma subjects with either a positive head CT (n=13), negative head CT (n=39) or non-head injury (n=23) to determine whether eye tracking would reveal the disconjugate gaze associated with both structural brain injury and concussion. Tracking metrics were then correlated to the clinical concussion measure SCAT3 in trauma patients. Results: Five out of five measures of horizontal disconjugacy were increased in positive and negative head CT patients relative to non-injured control subjects. Only one of five vertical disconjugacy measures was significantly increased in brain injured patients relative to controls. Linear regression analysis of all 75 trauma patients demonstrated that three metrics for horizontal disconjugacy negatively correlated with SCAT3 symptom severity score and positively correlated with total Standardized Assessment of Concussion (SAC) score. Abnormal eye tracking metrics improved over time towards baseline in brain injured subjects seen in follow-up. Conclusions: Eye tracking may help quantify the severity of ocular motility disruption associated with concussion and structural brain injury.

OBJECTIVE:To determine whether hospitalization is associated with subsequent cognitive decline or changes on brain MRI in a community-based cohort. METHODS:Baseline and follow-up cognitive testing (n = 2,386) and MRI scans with standardized assessments (n = 885) were available from a subset of white and black participants in the Atherosclerosis Risk in Communities study. Cognitive tests included the Delayed Word Recall Test (DWRT), Digit Symbol Substitution Test (DSST), and Word Fluency Test (WFT). Hospitalization characteristics were determined using ICD-9 codes. Regression models adjusted for demographics, education, comorbidities, and APOE ε4 were used to estimate the independent association of hospitalization with changes in cognition or neuroimaging. RESULTS:Over a mean 14.1 years between visits, 1,266 participants (53.1%) were hospitalized. Hospitalization compared with no hospitalization was associated with greater decline in DSST scores (1.25 points greater decline, p < 0.001) but no difference in DWRT or WFT score change. Each additional hospitalization, as well as a critical illness vs noncritical illness hospitalization, was associated with greater decline in DSST scores. A subset of participants (n = 885) underwent MRI scans separated by 10.5 years. Hospitalization (n = 392) compared with no hospitalization was associated with a 57% higher odds of increasing ventricular size at follow-up. Each additional hospitalization, as well as having a critical illness vs noncritical illness hospitalization, and having a hospitalization with major surgery vs no surgery was associated with greater odds of increased ventricular size. CONCLUSIONS:Cognitive decline and neuroimaging changes may occur after hospitalization, independent of baseline demographics and comorbidities.