Faculty Bibliography

Background: Sideline diagnostic tests for concussion are vulnerable to volitional poor performance ("sandbagging") on baseline assessments, motivated by desire to subvert concussion detection and potential removal from play. We investigated eye movements during sandbagging versus best effort on the King-Devick (KD) test, a rapid automatized naming (RAN) task. Methods: Participants performed KD testing during oculography following instructions to sandbag or give best effort. Results: Twenty healthy participants without concussion history were included (mean age 27 ± 8 years). Sandbagging resulted in longer test times (89.6 ± 39.2 s vs 48.2 ± 8.5 s, p < .001), longer inter-saccadic intervals (459.5 ± 125.4 ms vs 311.2 ± 79.1 ms, p < .001) and greater numbers of saccades (171.4 ± 47 vs 138 ± 24.2, p < .001) and reverse saccades (wrong direction for reading) (21.2% vs 11.3%, p < .001). Sandbagging was detectable using a logistic model with KD times as the only predictor, though more robustly detectable using eye movement metrics. Conclusions: KD sandbagging results in eye movement differences that are detectable by eye movement recordings and suggest an invalid test score. Objective eye movement recording during the KD test shows promise for distinguishing between best effort and post-injury performance, as well as for identifying sandbagging red flags.

Although policies to remove lead from gasoline have resulted in a substantial reduction in airborne lead, multiple industries are known to generate lead that is released in the air. The present study examines the extent to which residential proximity to a documented source of airborne lead is associated with intellectual and executive function in children. Data were available for n = 849 children from the Family Life Project. Geolocation for children's residences between birth and 36 months were referenced against the Environmental Protection Agency's Risk Screening Environmental Indicators (RSEI) database, which estimates exposure for each ½ mile grid in the contiguous United States. Instrumental variable models were employed to estimate causal associations between exposure and cognitive outcomes measured at 36, 48, and 60 months, using census-documented density of manufacturing employment as the instrument. Models of continuous lead dosage indicated small negative effects for both child IQ and executive function (EF). These results indicate that RSEI estimates of airborne lead exposure are meaningfully associated with decrements in cognitive development.

PURPOSE/OBJECTIVE:Tobacco-use is a causative or exacerbating risk factor for benign and malignant urologic disease. However, it is not well known how often urologists screen for tobacco use and provide tobacco cessation treatment at the population level. Therefore, we sought to evaluate how often urologists see patients for tobacco-related diagnoses in the outpatient setting and how often these visits include tobacco-use screening and treatment. MATERIALS AND METHODS/METHODS:We used the National Ambulatory Medical Care Survey (NAMCS) public use files for the years 2014-2016 to identify all outpatient urology visits with adults 18 years and older. Clinic visit reasons were categorized according to diagnoses associated with the encounter: all urologic diagnoses, a tobacco-related urologic condition, or a urologic cancer. Our primary outcome was the percentage of visits during which tobacco screening was reported. Secondary outcomes included reported delivery of cessation counseling and provision of cessation pharmacotherapy. RESULTS:We identified 4,625 unique urologic outpatient encounters, representing a population-weighted estimate of 63.9 million visits over three years. Approximately a third of all urology visits were for a tobacco-related urologic diagnoses and 15% were for urologic cancers. An estimated 1.1 million visits over three years were with patients who identified as current tobacco users. Of all visits, 70% included tobacco screening. However, only 7% of visits with current smokers included counseling and only 3% were prescribed medications. No differences in screening and treatment were observed between visit types. CONCLUSIONS:Urologists regularly see patients for tobacco-related conditions and frequently, though not universally, screen patients for tobacco. However, urologists rarely offer counseling or cessation treatment. These findings may represent missed opportunities to decrease the morbidity associated with tobacco use.

BACKGROUND:Pancreatic cancer (PC) is a complex disease in which both non-genetic and genetic factors interplay. To date, 40 GWAS hits have been associated with PC risk in individuals of European descent, explaining 4.1% of the phenotypic variance. METHODS:We complemented a new conventional PC GWAS (1D) with genome spatial autocorrelation analysis (2D) permitting to prioritize low frequency variants not detected by GWAS. These were further expanded via Hi-C map (3D) interactions to gain additional insight into the inherited basis of PC. In silico functional analysis of public genomic information allowed prioritization of potentially relevant candidate variants. RESULTS:We identified several new variants located in genes for which there is experimental evidence of their implication in the biology and function of pancreatic acinar cells. Among them is a novel independent variant in NR5A2 (rs3790840) with a meta-analysis p value = 5.91E-06 in 1D approach and a Local Moran's Index (LMI) = 7.76 in 2D approach. We also identified a multi-hit region in CASC8-a lncRNA associated with pancreatic carcinogenesis-with a lowest p value = 6.91E-05. Importantly, two new PC loci were identified both by 2D and 3D approaches: SIAH3 (LMI = 18.24), CTRB2/BCAR1 (LMI = 6.03), in addition to a chromatin interacting region in XBP1-a major regulator of the ER stress and unfolded protein responses in acinar cells-identified by 3D; all of them with a strong in silico functional support. CONCLUSIONS:This multi-step strategy, combined with an in-depth in silico functional analysis, offers a comprehensive approach to advance the study of PC genetic susceptibility and could be applied to other diseases.

BACKGROUND:Altered postinjury platelet behavior is recognized in the pathophysiology of trauma-induced coagulopathy (TIC), but the mechanisms remain largely undefined. Studies suggest that soluble factors released by injury may inhibit signaling pathways and induce structural changes in circulating platelets. Given this, we sought to examine the impact of treating healthy platelets with plasma from injured patients. We hypothesized that healthy platelets treated ex-vivo with plasma from injured patients with shock would impair platelet aggregation, while treatment with plasma from injured patients with significant injury burden, but without shock, would enhance platelet aggregation. METHODS:Plasma samples were isolated from injured patients (pretransfusion) and healthy donors at a Level I trauma center and stored at -80°C. Plasma samples from four separate patients in each of the following stratified clinical groups were used: mild injury/no shock (injury severity score [ISS] 2-15, base excess [BE]>-6), mild injury/with shock (ISS 2-15, BE≤-6), severe injury/no shock (ISS>25, BE>-6), severe injury/with shock (ISS>25, BE≤-6), minimal injury (ISS 0/1, BE>-6), and healthy. Platelets were isolated from three healthy adult males and were treated with plasma for 30 min. Aggregation was stimulated with a thrombin receptor agonist and measured via multiple-electrode platelet aggregometry. Data were normalized to HEPES Tyrode's (HT) buffer-only treated platelets. Associations of plasma treatment groups with platelet aggregation measures were tested with Mann-Whitney U tests. RESULTS:Platelets treated with plasma from patients with shock (regardless of degree of injury) had significantly impaired thrombin-stimulated aggregation compared with platelets treated with plasma from patients without shock (P = 0.002). Conversely, platelets treated with plasma from patients with severe injury, but without shock, had amplified thrombin-stimulated aggregation (P = 0.030). CONCLUSION:Shock-mediated soluble factors impair platelet aggregation, and tissue injury-mediated soluble factors amplify platelet aggregation. Future characterization of these soluble factors will support development of novel treatments of TIC.

BACKGROUND:Black heart transplant recipients have higher risk of mortality than White recipients. Better understanding of this disparity, including subgroups most affected and timing of the highest risk, is necessary to improve care of Black recipients. We hypothesize that this disparity may be most pronounced among young recipients, as barriers to care like socioeconomic factors may be particularly salient in a younger population and lead to higher early risk of mortality. METHODS:We studied 22 997 adult heart transplant recipients using the Scientific Registry of Transplant Recipients data from January 2005 to 2017 using Cox regression models adjusted for recipient, donor, and transplant characteristics. RESULTS:=0.1). CONCLUSIONS:Young Black recipients have a high risk of mortality in the first year after heart transplant, which has been masked in decades of research looking at disparities in aggregate. To reduce overall racial disparities, clinical research moving forward should focus on targeted interventions for young Black recipients during this period.

Kidney transplant (KT) outcomes for HIV-infected (HIV+) persons are excellent, yet acute rejection (AR) is common and optimal immunosuppressive regimens remain unclear. Early steroid withdrawal (ESW) is associated with AR in other populations, but its utilization and impact are unknown in HIV+ KT. Using SRTR, we identified 1225 HIV+ KT recipients between January 1, 2000, and December 31, 2017, without AR, graft failure, or mortality during KT admission, and compared those with ESW with those with steroid continuation (SC). We quantified associations between ESW and AR using multivariable logistic regression and interval-censored survival analysis, as well as with graft failure and mortality using Cox regression, adjusting for donor, recipient, and immunologic factors. ESW utilization was 20.4%, with more zero HLA mismatch (8% vs 4%), living donors (26% vs 20%), and lymphodepleting induction (64% vs 46%) compared to the SC group. ESW utilization varied widely across 129 centers, with less use at high- versus moderate-volume centers (6% vs 21%, P < .001). AR was more common with ESW by 1 year (18.4% vs 12.3%; aOR: _1.08 1.61_2.41 , P = .04) and over the study period (aHR: _1.02 1.39_1.90 , P = .03), without difference in death-censored graft failure (aHR _0.60 0.91_1.36 , P = .33) or mortality (aHR: _0.75 1.15_1.77 , P = .45). To reduce AR after HIV+ KT, tailoring of ESW utilization is reasonable.