Abstracts from John B. Graham Student Research Day

The John B. Graham Student Research Society

46th Annual Student Research Day

January 16, 2014

Slitrk Gene Expression Patterns in Developing Zebrafish Nervous System

Jennifer Round, Brittany Ross, Barbra Lom

The Slitrk family of leucine-rich repeat (LRR) transmembrane proteins bears structural similarity to the Slit and the Trk receptor families, which each exert well-established roles in directing nervous system development. Slitrks are less well understood, though they are highly expressed in the developing vertebrate nervous system. Moreover, slitrk variants are associated with several sensory and neuropsychiatric disorders, including myopia, deafness, obsessive-compulsive disorder (OCD), schizophrenia, and Tourette syndrome. Loss-of-function studies in mice suggest that Slitrks modulate neurite outgrowth and inhibitory synapse formation, though the molecular mechanisms of Slitrk function remain poorly characterized. As a pretext to examining the functional roles of Slitrks, we identified eight slitrk orthologs in zebrafish and observed that seven of the eight orthologs were actively transcribed in the nervous system at embryonic, larval, and adult stages. Similar to previous findings in mice and humans, zebrafish slitrks exhibited unique but overlapping spatial and temporal expression patterns in the developing brain, retina, and spinal cord. Zebrafish express Slitrks in the developing central nervous system at times and locations important to neuronal morphogenesis and synaptogenesis. Future studies will utilize zebrafish as a convenient, cost-effective model organism to characterize the functional roles of Slitrks in nervous system development.

Understanding Short Inter-pregnancy Intervals in Relation to Postpartum Contraception

Emily Bardolph, Christina Olson, Dr. Beat Steiner

Objective: The purpose of this study was to examine factors associated with short inter-pregnancy intervals (IPIs) in a largely underserved population in North Carolina.

Methods: A retrospective cohort study design was to review the charts of 114 women with short IPIs (<18mo) compared to 71 controls (IPI >18mo). This chart review represented a cross-section of Piedmont Health Services clinics. Hypotheses for factors associated with short IPIs were examined using chi-square tests.

Results: Rates of unplanned pregnancies were higher in women with short IPIs compared to controls, with a trend toward significance (p=0.07). No statistical difference in the rates of contraceptive counseling was found between the groups (p=0.25 prenatal, p=0.93 postpartum, p=0.11 both). Rates of counseling in the prenatal period were low overall for both groups. Clinic visit frequency, both prenatal and postpartum, was similar between groups. Documented uptake of long-acting, reversible contraception was similarly low between groups.

Limitations: Only information documented in charts could be quantified. Actual rates of contraceptive counseling and uptake might have been higher if obtained elsewhere or not documented.

Conclusions: Short inter-pregnancy intervals appear undesirable for patients, as indicated by higher rates of unplanned pregnancies among women with short IPIs. The prenatal period may be an area for quality improvement in counseling. Low rates of long-acting, reversible contraception uptake highlight an area for potential improvement in contraceptive management to prevent unplanned and/or poorly-spaced pregnancies.

A New Method of Invasive Measurement of Left Ventricular Diastolic Function

Ted Hodges, MS2; Louis Kolman, MD; George Stouffer, MD

Background: Abnormalities in diastolic filling of the left ventricle, referred to as diastolic dysfunction, are a common cause of cardiac morbidity. Echocardiography is the method most commonly used to assess diastolic function and characterizes diastolic filling as normal or abnormal based primarily on a comparison of blood flow across the mitral valve during early and late periods of diastole. This study whether a new variable, change in pressure (delta P) divided by change in time (delta T) during diastasis (the middle one-third of diastole) as measured during cardiac catheterization, would correlate with diastolic function as determined by echocardiography.

Methods: This was a retrospective study of consecutive patients who underwent left heart catheterization in the Cardiac Catheterization Laboratory at the University of North Carolina. Inclusion criteria were age between 18 and 80 years, an echocardiogram within 14 days of the catheterization and normal sinus rhythm with heart rate < 100 bpm during both left heart catheterization and echocardiogram. Exclusion criteria were cardiogenic shock or ST elevation myocardial infarction. Echocardiograms were reviewed and diastolic function graded based on established criteria (normal, grade 1, 2, or 3 dysfunction). Left ventricular pressure tracings obtained at the time of heart catheterization were analyzed as follows: diastole was divided into three equivalent intervals and the change in pressure divided by the change in time was calculated for each portion.

Results: There was no difference in age, weight, BMI or systolic blood pressure between patients with normal diastolic function (n = 25), grade 1 diastolic dysfunction (n = 52), grade 2 diastolic dysfunction (n = 98) or grade 3 diastolic dysfunction (n = 17). Left ventricular end diastolic pressure was similar in patients with normal, grade 1 or grade 2 diastolic dysfunction but higher in grade 3 diastolic dysfunction (15 ± 5, 14 ± 6, 19 ± 8 and 23 ± 9 mm Hg, respectively; p < 0.05 for comparison of normals and grade 3 dysfunction). Median ΔP/ΔT values during diastasis were lower in patients with normal diastolic function by echocardiography (0.0113 ± 0.0170 mm Hg/msec) than in patients with grade 1, 2 or 3 diastolic dysfunction (0.0191 ± 0.0178, 0.0232 ± 0.0328, 0.0662 ± 0.107 mm Hg/msec; p = 0.004 for difference among groups by ANOVA; all groups with diastolic dysfunction were significantly different from normal group by Dunn’s multiple range test). There was a linear correlation between delta P/delta T during diastasis and left atrial size, another echocardiographic feature of diastolic dysfunction (r = 0.222, P = 0.00188).

Conclusions: delta P/delta T during diastasis, obtained at the time of left heart catheterization, correlates with diastolic function as determined by echocardiography. More studies are necessary to determine whether diastolic function determined using this method has clinical utility.

Kwashiorkor and pregnancy: An unusual cause of fatty liver

Romin Bonakdar, Patricia Jones, Christopher McGowan, A. Sidney Barritt

Kwashiorkor is a severe form of protein-energy malnutrition seen most commonly in children in the developing world. Common gastrointestinal manifestations of kwashiorkor include intestinal atrophy and villus flattening, reduced synthesis of pancreatic enzymes and severe hepatic steatosis and hepatomegaly. We report the case of a 31-year-old woman with type 1 diabetes mellitus who presented at 16 weeks of pregnancy with kwashiorkor-induced fatty liver and synthetic liver dysfunction due to intentional caloric restriction. This condition is rarely seen in adults, especially in the United States of America, and this represents the first case of kwashiorkor described during pregnancy in the literature.

The Effect of Interoceptive Awareness and Diagnosis of Anorexia Nervosa on Susceptibility to the Rubber Hand Illusion

Mary Katherine Weinel

Introduction. Previous studies have reported that women with anorexia nervosa (AN) are more susceptible to the rubber hand illusion, “a perceptual illusion used to measure somatosensory processing deficits” compared to healthy women. Susceptibility to the rubber hand illusion is measured by a shift in perceived location of one’s index finger and skin temperature changes pre- and post-exposure to the task as well as a self-report questionnaire. This study aimed to assess whether there is a significant effect of an interoceptive-awareness-raising task on susceptibility to the illusion.

Methods. The rubber hand illusion was elicited twice (once during each of the two visits) in 19 healthy women (HC group) and 13 women with a current diagnosis of AN. Skin temperatures were taken before and during exposure to the illusion. Perceived locations of the index finger were measured before and after exposure. During the second visit, participants monitored and reported their perceived heart beats before undergoing the rubber hand illusion task.

Results. Women with AN had significantly lower scores on the Body Awareness Questionnaire compared to healthy control women. Contrary to previous research findings, women with AN endorsed less susceptibility to the illusion compared to healthy women based on results from a self-report questionnaire, and there were no significant differences in perceived index finger location changes (proprioceptive drift) between AN and HC groups.

Discussion. Nonsignificant results on the heart rate monitoring task and proprioceptive drift could have resulted from a change in methodology used in this study. On subjective measures, women with AN are less likely to report feeling susceptible to the illusion. Low body awareness and higher age may cause women with AN to be less likely to endorse susceptibility to the illusion. Because there were no significant differences in any measure across visits, no support was found for a possible learning effect or effect of the heart-rate monitoring (possible interoceptive awareness-raising) task.

Simvastatin, an HMG-CoA reductase inhibitor, exhibits anti-metastatic and anti-tumorigenic effects in endometrial cancer.

M. Schointuch, J.E. Stine, T. Gilliam, C. Zhou, X. Han, P.A. Gehrig and V.L. Bae-Jump

Objectives: Statin use has been associated with improved overall survival in women with endometrial cancer. However, if this is due to direct biologic effects or due to overall improved health is not clear. Thus, we evaluated the effects of simvastatin on cell proliferation, apoptosis, cellular stress and adhesion/invasion in human endometrial cancer cell lines and endometrial primary culture.

Methods: Two endometrial cancer cell lines (ECC-1 and Ishikawa) were used. Cells for primary culture were obtained from 5 patients who underwent endometrial cancer staging surgery. Cell proliferation was assessed by MTT assay. Cell cycle progression was evaluated by Cellometer. Apoptosis was evaluated by Annexin V-FITC assay using Cellometer. Invasion was demonstrated by a transwell invasion assay. ROS and cell adhesion were assessed by ELISA assay. Effects of stimvastatin on phosphorylated-S6, phosphorylated-p42/p44, pan-S6 and pan-p42/44 expression were documented by Western immunoblotting. Mitochondrial DNA damage was confirmed by QPCR.

Results: Simvastatin significantly inhibited cell proliferation in a dose-dependent manner in both ECC-1 and Ishikawa within 48 to 72 hours of exposure (IC50 range of 15-18 nM, p<0.001-0.05). Treatment with simvastatin resulted in G1 cell cycle arrest, induction of apoptosis, cellular stress and reduction in the enzymatic activity of HMG-CoA reductase. Western immunoblot analysis demonstrated that simvastatin decreased phosphorylation of S6 and p42/44 expression within 18 hours of exposure. In parallel, treatment with simvastatin reduced cell adhesion (p<0.001-0.03) and invasion (p<0.01-0.03) and increased mitochondrial DNA damage in both cell lines. Cell proliferation was also inhibited by simvastatin in a dose dependent manner in primary endometrial cancer cells (5/5, IC50 range 8-25 nM).

Conclusion: Simvastatin potently inhibited endometrial cancer cell growth via G1 arrest, cellular stress, mitochondrial DNA damage and increased apoptosis. These anti-tumorigenic effects may be partially mediated through inhibition of the mTOR and MAPK pathways. These findings are of particular interest as many women with endometrial cancer also have cardiovascular risk factors that could be mitigated by statin use.

African American College Students’ Attitudes About HIV and AIDS: An assessment of HIV knowledge and attitudes and current prevention strategies

Timica Campbell

Background: Until recently, African American college students were not considered to be a high risk population for HIV. Epidemiologic data reveals that the HIV incidence and prevalence in this group is significantly higher than that of white college students, and these numbers are rising.

Objective: To describe the HIV knowledge, attitudes and preventive or risk-taking behaviors of African American undergraduates in an attempt to better understand the causes for this increased incidence and to assess current prevention strategies.

Methods: In-depth interviews with African American undergraduate students from both Historically Black Colleges/Universities and Traditionally White Institutions and a systematic review and critical appraisal of the literature.

Findings: The media are the most influential source of information for HIV, but not enough of this information they present is distributed to students. Despite this lack of information, students are knowledgeable on the subject, though their answers show that many of the myths and misconceptions still exist about the virus. Students recognize the need for being tested for HIV, and are able to discuss testing with close friends, but the stigma that surrounds HIV-infected individuals and HIV testing is large enough to present a barrier to testing. Among other testing barriers, the most notable were a fear of a breech in confidentiality when seeking testing and a fear of knowing one’s HIV status. Some university policies and practices may contribute to these barriers.

Conclusion: The public health community must increase the amount of HIV knowledge promoted in the media. New methods of prevention must be developed that help students understand HIV risk and discussions of safe sex methods with partners.”

Bacterial cheating limits the evolution of antibiotic resistance

Hui Xiao Chao, Eugene Yurtsev, Manoshi Datta, Tanya Artemova and Jeff Gore

The widespread use of antibiotics has led to the evolution of resistance in bacteria. Bacteria can gain resistance to the antibiotic ampicillin by acquiring a plasmid carrying the gene beta-lactamase, which inactivates the antibiotic. This inactivation may represent a cooperative behavior, as the entire bacterial population benefits from removing the antibiotic. The cooperative nature of this growth suggests that a cheater strain—which does not contribute to breaking down the antibiotic—may be able to take advantage of cells cooperatively inactivating the antibiotic. Here we find experimentally that a “sensitive†bacterial strain lacking the plasmid conferring resistance can invade a population of resistant bacteria, even in antibiotic concentrations that should kill the sensitive strain. We observe stable coexistence between the two strains and find that a simple model successfully explains the behavior as a function of antibiotic concentration and cell density. We anticipate that our results will provide insight into the evolutionary origin of phenotypic diversity and cooperative behaviors.

Recruitment Tools for Preconception Cohort Studies: a Quantitative and Qualitative Analysis

Joylyn Daniel, Ashley Calingo, Anne Z. Steiner

Background

Prospective, preconception, cohort studies are considered the gold standard for assessing the impact of exposures on reproductive outcomes including fecundability, infertility, and miscarriage. However, identification, recruitment, and enrollment of subjects can be challenging and costly.

Methods

We present a quantitative analysis of the recruitment tools employed for Time to Conceive, a prospective time-to-pregnancy, cohort study of women ages 30-44 years of age and a qualitative analysis of focus groups conducted to assess potential phrases, images, and modes for recruitment.

Results

Distributed ads and emails recruited the highest percentage of participants (21.4% and 24.7% respectively). However, some modes of recruitment appeared to target or exclude certain races (P<0.001). Personal referrals were more common among White participants (17.6% of whites), and Hispanic women responded disproportionately to letters (17.2% of Hispanic participants). Black women responded to the study website (14.8% of Black participants) and television commercials (14.8% of Black participants). Focus groups identified 6 themes including: need to avoid the term ""fertility"" in recruitment materials, to use terms that target the planning stage of pregnancy, to use social media, to emphasize study benefits (pregnancy ultrasound and free pregnancy tests), and to utilize images relevant to the study.

Conclusion

Women can effectively be recruited to prospective time-to-pregnancy studies. Distributed ads and mass email are effective tools for recruiting large, diverse groups of women, while other recruitment tools may target specific races. Recruitment tools should avoid the use of the word “fertility” but should include the cost and benefits of study participation and use images relevant to the study purpose.

Augmenting Anti-Leukemia Immunity Through the Expression of Leukemia Associated Antigens in an Alphavirus System and the Delivery of BAFF

Margaret Williams, Wei Jia, Stefanie Sarantopoulos

Based on the previous findings that an activated potentially autoreactive B cell compartment present early post-hematopoietic stem cell transplant can target tumor cells for destruction, we have developed two systems for augmenting the anti-tumor effect. The first system can be used to express the tumor associated antigen (TAA), here we used FMS-like tyrosine kinase (FLT3), in an alphavirus-based virus-like replicon particle (VRP) system, which will be used as a tumor vaccine strategy in an acute myeloid leukemia (AML) mouse model to stimulate a B-cell immune response against FLT3 expressing tumor cells. At the same time, purified recombinant B cell activating factor of the TNF family (BAFF), will be administered to test whether BAFF can enhance the B cell response against the TAA of leukemia.

Portable Head CT

Yuxuan Mao; Jing Shan; Andrew Tucker; Laurel Burk; Pavel Chtcheprov, BS; Jianping Lu; et al

PURPOSE

This study describes the design of a novel carbon nanotube (CNT) based head CT. Current CT scanners are relegated to hospital use due to their size and moving gantry. CNT based x-ray sources allow novel gantry geometries unattainable by conventional sources. The lack of moving parts and ability to fit sources closely improve robustness and portability. A vehicle based CT scan to exclude hemorrhagic stroke enables early thrombolytic treatment, which is critical for better outcomes. Vehicle based CT scanners have already been demonstrated in limited applications. We evaluated a prototype CNT head CT scanner, with a conventional circular and a novel 16-sided polygon geometry, using standard phantoms and cadaveric heads.

METHOD AND MATERIALS

Imaging was performed with a linear array of 75 CNT cone beam sources (80 kVp) placed 1m opposite a digital detector. A rotation stage with either a Gammex 464 phantom, a skull phantom, or a cadaveric head was placed .25m from the detector. In the conventional CT setup, the object was rotated 200° while being scanned by a single source. In the 16-sided geometry (8 source-detector pairs), 20 sources in the array were fired in succession. The object was then rotated 22.5°. This was repeated 8 times until the object was scanned 200°. Exposures varied between 25-100 mAs. The reconstructed images were compared to those from a clinical Siemens Definition CT scanner using standard head protocol.

RESULTS

The SNR for Bone, Acrylic, Polyethylene, and Air elements of the Gammex 464 at 100 mAs were 10.4, 8.8, 7.6, and 4.0 respectively. CNR’s were 4.7, 1.0, 0.6, 4.2, and CT numbers were 898, 191, -106, and -799 respectively. lp/cm was 10. Radiation dose was 17 mGy. This compared favorably to conventional cone beam CTs. The different geometries produced images using skull phantom and cadaveric heads with good osseous detail.

CONCLUSION

This study is the first demonstration of a CNT based CT scanner for clinical applications. The images produced are on par with conventional CT in quality and dose. This is also the first report of a novel polygon geometry producing clinically useful CT images with cadaveric heads, showing that polygon geometries are feasible in general.

CLINICAL RELEVANCE/APPLICATION

This study demonstrates the potential imaging utility of the carbon nanotube based x-ray sources in a clinical CT application.

HIV Diversity: A Useful Biomarker for HIV Incidence Estimation

Matthew M. Cousins, Jacob Konikoff, Oliver Laeyendecker, Thomas C. Quinn, Ron Brookmeyer, and Susan H. Eshleman

BACKGROUND: Multi-assay algorithms (MAAs) can be used for cross-sectional HIV incidence estimation. A disadvantage of many MAAs is that they require CD4 cell count data, which must be obtained at the time of sample collection from all HIV-infected individuals in the cross-sectional survey. We studied HIV diversity as an alternative biomarker to replace CD4 cell count data and evaluated the performance of 4-assay MAAs that include two serologic assays, viral load, and the high resolution melting (HRM) diversity assay.

METHODS: The HRM diversity assay is a high-throughput assay that does not require sequencing; diversity measures are reported as HRM scores. HRM scores were determined for eight regions of the HIV genome (2 in gag, 1 in pol, and 5 in env). MAAs were evaluated that used the following assays: BED capture enzyme immunoassay (BED-CEIA), BioRad-Avidity assay, viral load, and the HRM diversity assay. HRM scores from different regions and varied region-specific HRM diversity assay cutoffs were examined. Mean window periods for MAAs were determined using 1,782 samples from three cohorts. Cross-sectional incidence estimates obtained using the MAAs were compared to incidence rates observed in three longitudinal studies.

RESULTS: The performance of the new HRM-based MAA was nearly identical to a previously-optimized MAA that included CD4 cell count. The HRM-based MAA had a mean window period of 154 days and provided cross-sectional incidence estimates that were similar to those based on longitudinal follow-up.

CONCLUSIONS: HIV diversity is a useful biomarker for HIV incidence estimation. MAAs that include the HRM diversity assay can provide accurate HIV incidence estimates using stored plasma or serum samples, without the need for CD4 cell count data.

Diagnosing HIV Infection in Primary Care Settings: Missed Opportunities

Tammy Chin, BS, Charles Hicks, MD, Gregory Samsa, PhD, and Mehri McKellar, MD

In the United States, 20% of HIV-infected persons are unaware of their diagnosis. Improved application of HIV screening recommendations in healthcare settings may facilitate diagnosis. Clinical patient data and previous healthcare visits were reviewed from medical records of newly diagnosed HIV-infected persons in Durham County, North Carolina, who initiated HIV care at Duke University Medical Center in 2008-2011. Comparisons were made to similar data from 2002-2004 using the Pearson’s chi-square test and logistic regression. 101 consecutive newly diagnosed patients were identified: 67 males; 73 black, 20 white, and 8 Hispanic/Latino. Mean age was 39 years (range, 17-69), and 73 had health insurance. Median baseline CD4 count was 313 cells/L (range, 4-1302), and HIV-1 viral load was 45,700 copies/mL (range, 165-10,000,000). One-third had a baseline CD4 count <50 cells/L, and 15% presented with opportunistic infections. Compared to patients newly diagnosed in 2002-2004, significantly greater proportions were black and less immunocompromised in 2008-2011. Most had been seen at least once by a healthcare provider in the year prior to HIV diagnosis: 72 had 1 prior visits, and 47 had 2 visits. Among those with prior visits, 37/72 (51%) were seen in an emergency department on the first or second visit. Men were three times more likely than women to be diagnosed at their first healthcare encounter (p=0.03, OR=3.2). Despite CDC recommendations for widespread HIV screening in healthcare settings, HIV diagnosis remains delayed, even among those with frequent healthcare encounters. Educating providers and removing barriers to HIV screening may improve this problem.

Self-Reported vs. Performance-Based Assessments of Physical Function Among Older Adults in the Emergency Department

Kyle Roedersheimer, Greg F. Pereira, Timothy F. Platts-Mills

Objectives: Accurately determining the mobility of independent-living older adults is an essential step in assessing whether they may be safely discharged from the emergency department (ED). We assessed the accuracy of self-reported ability to get out of bed, walk 10 feet, and return to bed among older ED patients.

Methods: Patients were enrolled during 32 randomly selected 4-hour blocks over 8 weeks. Time blocks ran from 9am-1pm, 1pm-5pm, and 5pm-9pm. Cognitively intact patients aged 65 years and older who were not nursing home residents and were not critically ill were eligible. Consenting participants were asked whether they could get out of bed, walk 10 feet, turn around, and get back in bed without assistance and if not whether they could do perform this task with a cane or walker or with human assistance. Patients were then asked to perform the task.

Results: Of 174 patients screened, 112 met eligibility criteria and consented to participate. Participants were white (67%), female (58%), and discharged (52%). Routine use of a cane or walker was reported by 34%. Among those who said they could perform the task without assistance, 3% required a cane or walker and 3% could not walk even with human assistance. Among those who said they could perform the task with a cane or walker, 60% required either human assistance or could not perform the task. Among those who said they could perform the task with human assistance, 66% were unable to perform the task even with human assistance.

Conclusion: Older ED patients who reported needing assistance to perform a simple task necessary for independent living often underestimated the amount of assistance they would need or were unable to perform the task even with assistance. For older patients who require assistance with ambulation, direct observation of ambulation by emergency providers may improve decision making regarding disposition and the need for in-home care.

An Evaluation of Prophylactic Treatments to Prevent Post Traumatic Joint Stiffness

William M. Efird; Patrick J. Kellam; Shawn Yeazell; Paul Weinhold, PhD; Laurence Dahners MD

Objectives: Arthrofibrosis poses a major obstacle to restoring joint function after trauma. This study evaluated methods which might provide prophylaxis against arthrofibrosis by targeting components of the inflammatory process that induces fibrosis: 1. oral administration of montelukast (leukotriene inhibitor) 2. intra-articular injections of forskolin (blocks TGF-beta 1)3. intra-articular injections of triamcinolone acetonide (steroid).

Methods: Forty-eight Sprague-Dawley rats underwent surgical knee trauma with postop immobilization in full flexion. Four treatment groups: control (CTL), oral montelukast (3.75 mg/kg/day) (MLK), day 1 and 4 intra-articular forskolin injections (0.6 mg/kg) (FSK), and day 1 and 4 intra-articular triamcinolone injections (0.68 mg/kg) (STR). Rats were sacrificed after 14 days and femorotibial contracture angles were measured with the posterior capsule intact, the posterior capsule cut, and with cruciate ligaments cut. Angles were measured with a 0.015Nm extension moment applied to the knee.

Results: All treatment groups had significant reductions in contracture angle compared to the control (p<0.05). The mean contracture angles with the posterior capsule intact were 32º(CTL), 20º(MLK), 22º(FSK), and 7º(STR). The contractures with the posterior capsule cut were 28º (CTL), 19º (MLK), 20º (FSK), 5º(STR). With the cruciate ligaments cut the contractures were 18º(CTL), 12º(MLK), 10º (FSK), -3º(STR). There was no significant difference between the FSK and MLK measurements in any group. The STR group was significantly better than FSK and MLK(p<0.05).

Conclusions: Triamcinolone injections provided dramatic reductions in stiffness. Both forskolin and montelukast provided significant, though lesser, reductions in stiffness. While triamcinolone contracture angles were significantly better in all measurements, the novel treatments of forskolin and montelukast provided encouraging results and should be studied further.

Examining the Associations of Parents’ and Teenagers’ Attitudes of Blood Donation and Intentions to Donate Blood

Meredith Johnson, Kimberly Jacob Arriola, Eric Nehl

Background. At present, approximately one-third of the U.S. population is eligible to donate blood. However, only a small fraction does donate blood. With a depleted blood donor pool, there is a foreseeable shortage in the blood supply. The inclusion of minors with parental consent is the most recent strategy to increase the blood donor pool. In order to increase the amount of young donors, a deeper understanding of the attitudes and intentions among parents and teenagers is essential. The present study seeks to examine relationships between parental and teenage attitudes and intentions to donate blood, and explore the importance of potential barriers to donating blood.

Methods. A cross-sectional survey was administered to parents and their dependent teenagers between 14 and 17 years of age. Survey items assessed one’s attitudes and intentions to donate blood, and the degree of importance for potential barriers in the blood donation process. Correlational statistical analyses were performed to analyze potential associations.

Results. From the 29 paired surveys used for analysis, results of a Pearson correlation suggest that there is no statistically significant association between parental attitudes and intentions to donate blood, or teenage attitudes and intentions to donate blood. When controlling for demographic characteristics in a linear regression, there is no statistically significant association between attitudes and intentions to donate blood. Moderate agreement was observed between parental and teenage cognitive attitudes of blood donation (κ =0.60, p < 0.05). Barriers related to fear were deemed low importance among parents and teenagers, while barriers related to the logistics of the blood donation process were deemed high importance.

Discussion. Among the participants in the study, parents and teenagers seem to have similar attitudes and intentions to blood donation. When targeting minors for blood donation, it is important to include parents in the interventions.

Going Local: Successes in Online Recruitment of MSM for Biomedical HIV Prevention Research

Lindsey Buckingham, Chelsea D. Voytek, Julie Becher, David S. Metzger, Ian Frank

Background: Online and mobile-phone based social networking applications can be valuable tools for recruitment of human subjects to interventional clinical trials. We report successes using various online social networking sites, especially with the employment of GRINDR, a mobile phone social/sexual networking application (app), to recruit men who have sex with men (MSM) to a phase 2b HIV vaccine trial.

Methods: The University of Pennsylvania HIV Vaccine Trials Unit (Penn HVTU) has utilized online recruitment methods since July of 2010. In October 2012, we combined existing national recruitment images/messages with Philadelphia-specific language and imagery to advertise on the social/sexual networking mobile phone app GRINDR. To analyze the ability of this app to engage eligible participants we compare this strategy to other online recruitment methods.

Results: While advertising on GRINDR, the rate of contact and engagement of eligible participants increased dramatically. In 17 days of advertising, the phillyvax.org website was viewed over 18,000 times and 329 unique contact forms were completed. Staff spoke to 233 participants for a phone screen and 122 were eligible. Fifty-nine came to the clinic for face-to-face screens and 16 remained eligible. Our site enrolled all 16 participants for our 2 year interventional trial. GRINDR recruits comprised 22.5% of enrolled participants contacted via online methods.

Conclusion: Advertising via mobile phone apps can be a valuable method for recruitment of human subjects to biomedical HIV prevention trials. The Penn HVTU saw significant success when this recruitment strategy employed Philadelphia-focused imagery combined with national images and language.

The Use of Biomarkers to Predict Survival In Patients with Severe Renal Artery Stenosis

Rick Stouffer, Josh Dilley

Atherosclerotic renal artery stenosis (RAS) is the narrowing of one or both renal arteries, which carry blood from the aorta to the kidneys. RAS is found in 7% of the population whom are over 65 years of age, up to 40% of patients with peripheral vascular disease and approximately 12% of patients undergoing cardiac catheterization. Patients with RAS have a high risk of cardiovascular death, myocardial infarction and stroke. The leading cause of death in patients with RAS is cardiovascular events. Dismal outcomes for patients with RAS are a consistent finding in clinical studies. Despite the poor outcomes observed in patients with RAS, no biomarkers have been identified that predict survival. This study used data obtained from a clinical study performed between 2004 and 2006 to see if biomarkers of systemic inflammation or activation of renin-angiotensin system are useful in predicting survival in severe RAS. Markers of systemic inflammation (high sensitivity c-reactive protein and high sensitivity interleukin-6), renin-angiotensin system activation (renin) and renal function (creatinine) were measured in 33 patients with severe RAS undergoing unilateral percutaneous revascularization. Survival was determined using electronic medical records and on-line data bases. At a mean follow-up of 8.2 years, 20 patients were alive and 13 had died. None of the variables were found to correlate with survival in the patients. Increasing the study size would provide greater statistical power and allow better determination of the variables that influence survival in patients with severe renal artery stenosis.

Pediatric Fellows’ Participation in Therapeutic Camp: A Mixed-Methods Approach

Marley Burns, Nicole Fenton, Karina Javalkar, Sarah Cohen, Maria Ferris

Background: Fellows’ experiences at therapeutic camp and the impact on their subspecialty selection have not been characterized.

Purposes: This study uses a mixed-methods approach to characterize the demographics of fellows who have participated in a therapeutic camp, to assess the potential impact of the camp experience on subspecialty choice, and to understand the broader impact of the camp experience.

Methods: Pediatric fellowship directors from all ACGME programs in 18 subspecialties were asked to forward an anonymous 13-question online survey about therapeutic camps to their fellows. Information was collected on the type of residency training, type of fellowship, gender, and details of the fellows’ therapeutic camp experience as well as qualitative feedback on their camp experience and what effect camp had on their subspecialty choice. Quantitative and qualitative analyses were conducted.

Results: A total of 382 fellows participated in this study. The majority of fellows had never participated in a therapeutic camp (261, 68.3%). Of those who had not participated in camp, 201 (77.0%) reported interest in having this experience. Fellows who attended camp were significantly more likely select a chronic illness subspecialty (X2=.92, p=.05). Fellows who were pursuing an “intense†subspecialty were significantly less likely to have attended camp (X2=6.77, p=.001).

Qualitatively, fellows felt camp was a rewarding experience, a time of medical growth, and a means of appreciating the chronically ill patient as a normal child. Many fellows who attended camp reported that the experience helped them choose or reaffirmed their subspecialty choice.

Conclusions: Therapeutic camps are a valuable experience to trainees and may encourage them to pursue subspecialty training that focuses on chronic illness. Pediatric programs may want to consider adding a rotation at therapeutic camp as part of fellowship training.

Round Window Electrocochleography (ECoG) and Speech Outcomes in Adult Cochlear Implant Patients

Joseph H McClellan, BS; Eric J Formeister, MS; William H Merwin III, BS; Baishakhi Choudhury, MD; Craig A Buchman, MD, FACS; Oliver F Adunka, MD, FACS; Douglas C Fitzpatrick, PhD

Speech outcomes after cochlear implantation (CI) demonstrate substantial variability. Recently, the magnitude of Electrocochleography (ECoG) signals recorded intraoperatively from the round window (RW) was shown to account for almost half of the variance in postoperative word scores. The present study seeks to determine if including previously known predictive factors such as pure tone average (PTA) and duration of hearing loss (DHL) improves the correlation. RW ECoG was performed in adult patients undergoing CI. The magnitudes of the ongoing response across multiple frequencies at 85-95 dB HL were summed to obtain the total response (TR). A multiple linear regression analysis was used to correlate the TR, PTA, age and DHL with postoperative CNC word scores. Significant correlations with CNC word scores were found for TR (r2=0.44, p<.001, n=24) and PTA (r2=0.21, p=.024). However, when combined in a multiple regression the correlation was not significantly different from TR alone (TR, adjusted-R2=0.41 vs. TR and PTA, adj-R2=0.40; extra sum of squares (ESS) test: F(1,21)=0.40, p=0.53). Age and DHL did not significantly correlate with CNC scores, and the addition of these data did not significantly improve the model (adj-R2=0.41; ESS test: F(3,19)=1.01, p=0.41). These results suggest that intraoperative ECoG measurements largely contain the predictive information provided by preoperative audiometric tests and biographical information such as duration of hearing loss.

Understanding Indoor Tanning Behavior Among Sorority Women

Alexandra Zeitany B.S., Seth Noar Ph.D., Brenda Morales-Pico, B.S., Jessica Myrick, M.A., Nancy Thomas, M.D., Ph.D.

The indoor tanning industry has grown immensely in recent decades and multiple studies reveal that young, white women are particularly likely to go indoor tanning. The data also reveal increases in melanoma among precisely this group – with indoor tanning behavior the likely culprit. But what motivates young women to frequent these indoor tanning facilities remains unclear. The goal of this study was to develop and validate a comprehensive, multi-dimensional, theory-based outcome expectations measure to advance the understanding of the sets of beliefs that underlie indoor tanning behavior among young women. We worked closely with the Panhellenic Council at a large southeastern university and invited all Panhellenic sororities to participate in our study (N=1,805). Incentives for chapter participation were provided. Data was collected via web-based surveys for 3 weeks. A comprehensive scale assessing indoor tanning outcome expectations was developed. Six positive outcome expectation factors and five negative factors were identified. These subscales were reliable (coefficient alpha .76 – .93) and were significantly (mostly at p<.001) correlated with a set of established measures, including intention to tan indoors. While positive outcome expectations generally had the larger effect sizes between tanners and non-tanners, the two subscales with the largest differences across the groups of tanners were mood enhancement (positive) and psychological/physical discomfort (negative). Interestingly, perceived health risk had the smallest difference across the groups compared with all other subscales. Our data suggests that interventions focusing solely on skin cancer risk may not be persuasive, as many tanners appear to already be aware of the risks. Reducing positive expectations of tanning appears to be more influential than increasing the negative expectations; particularly in regards to mood enhancement, convenience factors, and appearance motivations. Future studies can apply this scale to better understand what beliefs to target in communications to deter indoor tanning, as well as use the scale to assess whether interventions were successful in changing the targeted beliefs.

Induction of Akt by Low Intensity Vibration Does Not Require Focal Adhesion Mechanosome in Mesenchymal Stem Cells

Sean Miller, Gunes Uzer, Natasha Case, Janet Rubin

Background/Objective: Mechanical loading, including low intensity vibration (LIV), is an anabolic stimulus for bone, biasing mesenchymal stem cell (MSC) lineage towards osteogenesis. Substrate strain, analogous to strenuous exercise, has been shown to limit MSC adipogenesis by generating βcatenin via a Wnt independent process. The critical pathway stimulated by strain is initiated at focal adhesions where Fyn/FAK activation leads to mTORC2 activation of Akt. While LIV is virtually absent of strain, signaling pathways activated by LIV influencing MSC fate also involve nuclear trafficking of βcatenin. The mechanism by which LIV promotes βcatenin nuclear entry is poorly understood. Here we asked if LIV utilized a similar pathway to strain, initiated at focal adhesions and resulting in phosphorylation and inhibition of GSK3beta.

Methods: Marrow derived MSCs were treated with LIV (0.7 g, 90 Hz, 20 min) and phosphorylation of Akt, GSK3beta, and FAK was analyzed by Western blot. siRNA against Fyn and inhibitors for Src, mTOR, and FAK were utilized to characterize LIV activated pathways.

Results: Compared to non-vibrated controls, LIV activated Akt (+77%) and increased GSK3beta phosphorylation (+28%). Both pAkt and pGSK3beta were reduced when MSC were pretreated with mTOR inhibitor (pAkt to -86% and GSK3beta to -69%, p<0.05). However, in contrast to strain, LIV-induced Akt activation and GSK3beta inhibition were unaffected by the presence of a Src inhibitor (e.g., Fyn was not required). We confirmed Fyn-independence: siRNA against Fyn did not impair LIV induced phosphorylation of either Akt or GSK3beta. Further, although FAK was also phosphorylated by LIV (+22%), inhibition of FAK had no significant effects on pAkt, suggesting that LIV might not activate Akt at focal adhesions.

Conclusions: Our data suggest that LIV activates βcatenin through mTOR regulated inhibition of GSK3beta. The proximal events leading to mTORC2 activation, however, depart from strain induced pathway components: LIV proximal events leading to Akt activation do not require Fyn or FAK, components of the focal adhesion mechanosome. As such, our data demonstrate that cells sense substrate strain and LIV via different mechanisms. Considering the anabolic potential of LIV as a non-pharmacologic intervention for bone loss, an improved understanding of LIV induced signaling will be critical for clinical translation.

Criterion-related validity of the Sociability Factor among children with autism spectrum disorder

Elise Stephenson, Marina Spanos, Linmarie Sikich

Background: The sociability factor questionnaire (SF) is a caregiver-rated assessment of reciprocal social interaction (RSI) in children and adolescents with autism spectrum disorder (ASD). This instrument was developed to improve upon current outcome measures used in psychotherapeutic clinical trials that do not focus on sociability or have not been shown to be sensitive to clinical change.

Aims: To assess the criterion-related validity of SF and measure whether it is sensitive to clinical change. The construct validity of the Clinical Global Impressions-Improvement score (CGI-I) was also evaluated.

Methods: Criterion-related validity was measured by correlating SF with the social withdrawal sub-score of the Aberrant Behavior Checklist (ABC-SW), the raw SOCDEF score of Pervasive Developmental Disorders Behavior Inventory-Screening Version (PDDBI-SV), and the total raw and subscale scores of the Social Responsiveness Scale (SRS), three validated outcome measures for RSI in children and adolescents with ASD. Correlations between SF and both IQ and age were calculated to determine whether change in SF is independent of these secondary variables. Sensitivity to change was measured by correlating SF with CGI-I and the construct validity of CGI-I was measured by correlating it with change in the Clinical Global Impressions-Severity score (CGI-Sdiff¬).

Results: Pearson correlations between SF and ABC-SW, PDDBI-SV, and SRS were 0.74, 0.72, and 0.55, respectively (p<0.0001). SF was not associated with age (r = 0.14) or IQ (r = -0.05).

Neither SF nor CGI-Sdiff were correlated with CGI-I (r = 0.02, r = 0.06).

Conclusions: SF was highly correlated with ABC-SW, PDDBI-SV, and SRS while independent of age and IQ, supporting its criterion-related validity. The construct validity of CGI-I as a measure of change in children with ASD could not be confirmed, suggesting that the lack of correlation between SF and CGI-I is insufficient to disprove its sensitivity to change.

Endometrial cancer outcomes in diabetic women treated with metformin, statins and aspirin

Stuart Richard Pierce, MD, Kemi Morenikeji Doll, MD, Brittany Davidson, MD, Courtney Lee, B.S., Emily M. Ko, MD, MSCR, Anna C Snavely, PhD, Paola A. Gehrig, MD, Angeles Secord, MD, Laura Jean Havrilesky, MD and Victoria L. Bae-Jump, MD, PhD

Objectives:

The anti-diabetic drug, metformin, has shown promising anti-tumorigenic effects in pre-clinical studies, and clinical trials are underway in endometrial cancer (EC) patients. Emerging evidence suggests that metformin, statins, and aspirin may improve overall survival in women with EC. Thus, our goal was to evaluate the contributory effect of statins and aspirin, in combination with metformin, on outcomes in diabetic women with EC.

Methods:

We conducted an IRB-approved retrospective analysis of all women treated for EC at two academic institutions between 1/1997 and 7/2012. Demographic and clinical data were abstracted from medical records. A cohort of diabetic EC patients treated with metformin was identified. Further division within this cohort included patients treated with statins or aspirin. Fisher’s exact tests and Wilcoxon two-group tests were used. Cox regression modeling analyzed progression-free survival (PFS), time-to-progression (TTP) and overall survival (OS).

Results:

1995 women diagnosed with EC in the study period, 494 (25%) were women with DM comprising the study cohort. There were 282 (57%) metformin, 232 (46%) statin, and 165 (33%) aspirin users. Metformin use was associated with better OS (p<0.0002, HR 0.50, 95% CI: 0.34-0.72) and better PFS (p=0.0036, HR 0.61, 95% CI: 0.43-0.85), but not TTP. After adjusting for stage, grade, BMI, age, and treatment, metformin remained significantly associated with better OS (HR 0.49, 95% CI: 0.34-0.71) and better PFS (HR 0.60, 95% CI: 0.43-0.84), Aspirin or statin use alone was not associated with OS, PFS or TTP. Aspirin or statin use among metformin users had no additive benefit over metformin alone.

Conclusions:

Metformin remained significantly associated with improved OS and PFS in diabetic patients, and this persists in models accounting for the use of aspirin and statins. The resilience of metformin’s association with improved outcomes further supports its role in EC treatment and management, particularly in high-risk diabetic populations.

Development of a chimeric antigen receptor (CAR) to target Ewing’s sarcoma via CD276

Paola Lopomo, Dimiter Dimitrov, Waleed Haso, Zhongyu Zhu, Bradley St. Croix, Crystal Mackall, and Rimas Orentas

Ewing sarcoma is one of the deadliest pediatric cancers. Between 50% and 70% of patients are cured at primary diagnosis, however the 10-year relapse-free survival rate is a mere 30% for patients with metastasis to the lung and 16% for patients with metastasis to the bone. CD276, also known as B7H3, was first described as a co-stimulatory molecule of the B7 family. It has been shown to both inhibit and enhance T cell proliferation. CD276 can also be found on osteosarcoma, neuroblastoma, and Ewing sarcoma. Our aim was to create an immunotherapeutic approach for Ewing sarcoma based on its prominent expression of CD276. We molecularly cloned antibody-derived single-chain variable fragment (scFv) sequences to those encoding T cell transmembrane and signaling motifs (CD28 and CD3-zeta) to create a CAR, and we created retroviral gene vectors for the transduction of activated T cells. We isolated CD276-specific scFv from a human B cell yeast display cDNA library. Three anti-CD276 scFv candidates were analyzed and found to be of varying affinity for the CD276 antigen. The three scFvs were each placed into a CAR expression vector, and activated human peripheral blood mononuclear cells were transduced with this vector. CAR expression on transduced T cells was demonstrated by staining for the CH2CH3 domain, which was included in the CAR construct, by flow cytometry. Anti-CD276 CARs generated in this manner were able to lyse both CHO cells transfected to express recombinant CD276 and CD276(+) patient-derived Ewing sarcoma lines in a chromium release assay. Interestingly, lytic activity did not correspond to the affinity of the scFV domains. Looking forward, we plan to optimize a CD276-specific CAR and to evaluate its potential to treat EWS in pre-clinical models.

Combination of Photodynamic Therapy and Hyperthermia for the Treatment of Malignant Pleural Mesothelioma

Joseph Friedberg, Michael Tenuto, Warren Naselsky

Malignant pleural mesothelioma is an incurable form of lung cancer which currently has very few viable treatment options. Recent evidence suggests that surgical resection with adjuvant intraoperative photodynamic therapy is able to extend the lives of patients with mesothelioma.1,2 In order to further advance this therapeutic option, the hypothesis that combining photodynamic therapy with hyperthermic conditions would synergistically enhance its ability to kill mesothelioma tumor cells was tested. Mice harboring subcutaneous flank tumors derived from AB12 mesothelioma cells, were treated with Photofrin photosensitizer 24 hrs prior to photodynamic therapy laser treatment. An additional cohort of mice had their flank tumor submerged in 43.5 C water during the above laser treatment. Tumor volume was tracked for one week following all treatments. The AB12 flank tumor exhibited consistent growth in those mice that didn’t receive treatment, indicating its viability as a tumor model. Mice exposed to body temperature water showed decreased tumor growth after one week as compared to those mice treated with hyperthermia. These results indicate that hyperthermia alone is not successful at controlling the growth of mesothelioma in mice models.

Causes of Rotavirus Vaccine Failure in Zambian Children: Study Overview

Seth Congdon, Roma Chilengi

Diarrhea caused by rotavirus infection kills over half a million children worldwide each year. In Zambia, diarrhea is the third leading cause of under-5 mortality, and rotavirus accounts for over a quarter of these deaths. Zambia has recently introduced the rotavirus vaccine RotarixTM into its national immunization program. For reasons that are poorly understood, RotarixTM has been found to be less efficacious among children in poor, developing countries as opposed to children in middle-income and industrialized nations, and efficacy varies widely across developing countries. In order to investigate possible causes of vaccine failure, we are conducting a prospective, open-label, nonrandomized observational study of infants receiving the RotarixTM vaccine in Lusaka, Zambia. The study has three objectives: 1) Evaluate the contribution of maternal immune factors to failed infant anti-rotavirus antibody seroconversion following vaccination; 2) Evaluate the contribution of maternal and infant factors to post-vaccination breakthrough severe rotavirus gastroenteritis; 3) Monitor the molecular epidemiology of breakthrough rotavirus infection among vaccinated infants. 420 mother-infant pairs will be enrolled as they visit Kamwala Health Centre in Lusaka for routine immunizations. Study participants will be followed until one year after the final participant has been enrolled. At present, the enrollment target is halfway reached. We hypothesize that maternal anti-rotavirus antibodies passed to infants in breastmilk lead to failed seroconversion by reducing vaccine titer, as RotarixTM is an attenuated live virus vaccine.

Can family caregivers screen for delirium in persons with dementia? Designing a delirium decision-making tool for informal dementia caregivers

Brendan Payne, Philip Sloane, Anna Beeber

Background: Dementia progression increases susceptibility to and severity of delirium while simultaneously impairing communication and decision-making capacity. Consequently, family and other informal caregivers often must evaluate, manage, and communicate with health care providers about signs of delirium in people with dementia. Yet existing instruments for delirium evaluation tend to be too clinical or research-focused, so informal dementia caregivers lack tools to help them identify delirium. The objective of our study was to address this discrepancy by designing a decision-making tool to help informal dementia caregivers identify delirium.

Methods: A nine-member caregiver advisory panel determined the formatting and content criteria for the delirium decision-making tool. To identify content, we searched UpToDate and PubMed for studies and reviews that examined diagnostic criteria of delirium and delirium detection tools. Based on this review and the criteria established by the advisory panel, we constructed an evidence-based delirium decision-making tool that could be used by informal dementia caregivers. The drafted tool was revised by medical professionals and will be field-tested as part of a randomized trial over the next 3 years.

Results: The evidence-based delirium decision-making tool for informal dementia caregivers includes the following: 1) concise caregiver education on the definition and common causes of delirium; 2) a six-item survey describing dementia-specific signs and examples of delirium; 3) simple instructions for quickly interpreting the survey results; and 4) access via hyperlink to a caregiver guide for understanding delirium in people with underlying dementia.

Conclusions: If field-testing demonstrates use, sensitivity, and specificity, the delirium decision-making tool may empower informal dementia caregivers to facilitate more reliable delirium diagnoses.

Myeloid-Derived Suppressor Cell Mediated Induction of Th2 Polarization in Head and Neck Cancer

Kola Agboola, BS; Grace Kim Austin, MD; Karen Mckinnon, Ph.D.; Jonathan Serody, MD; Adam Zanation, MD

Background: Myeloid-derived suppressor cells (MDSCs) are a subset of immunologic cells that hinder anti-tumor immune responses through release of cytokines and subsequent induction of M1/Th1 to M2/Th2 polarization of macrophages and T cells. Human papillomavirus (HPV) associated head and neck squamous cell carcinoma (HNSCC) have been shown to have larger MDSC populations compared HPV-negative HNSCC, potentially resulting in modified lymphocyte polarization and immune activity. We hypothesized that HPV-associated HNSCC would have increased gene expression of Th2 cytokines (e.g. IL4, IL10, IL13, and TGFβ1) and decreased expression of Th1 associated cytokine IL12, compared to HPV-negative HNSCC and tonsillar tissue.

Methods: Cryopreserved lymphocytes from HNSCC (HPV-, HPV+) and tonsil samples, previously acquired through an IRB-approved study, were used in our investigation. RNA extraction and RT-PCR were performed to produce cDNA complements of each sample. Taqman qRT-PCR analysis of cDNA samples was used to quantify expression of target genes relative to the housekeeping gene GADH.

Results: Eleven patient samples were included in this analysis: tonsils (n=4), HPV- (n=3), HPV+ (n=4). TGFβ1 [copy #]/GAPDH [copy #] ratios were 9.6270E-03 ± 7.9897E-03 and 1.8783E-02 ± 1.5507E-02 for HPV- and HPV+ samples, respectively. This upward trend was found to be insignificant (pvalue= 0.200). IL10 [copy #]/GAPDH [copy #] ratios were 2.8926E-03 ± 4.3112E-03 and 2.1027E-03 ± 1.8133E-03 for HPV- and HPV+ samples, respectively. This difference was found to be insignificant (pvalue= 0.444). IL12 [copy #]/GAPDH [copy #] ratios were 5.49483E-05 ± 2.38627E-05 and 2.0202E-04 ± 2.3645E-04 for HPV- and HPV+ tumor, respectively. This difference was insignificant (pvalue= 0.091). Detectable levels of IL4 and IL13 mRNA transcripts were not found.

Conclusions: We did not observe the hypothesized differences in M1/M2 gene transcript levels between HPV+ and HPV- HNSCC. We attribute this unexpected result primarily to the low cellular viability and subsequent RNA degradation of the cryopreserved samples.

Painful down-and-out eye in a diabetic patient

Jonathan Manhard

Diabetic ophthalmoplegia is a rare complication of diabetes mellitus most commonly arising from oculomotor nerve palsy. Poor glycemic control over time results in small vessel ischemia of the oculomotor nerve. This cranial mononeuropathy classically presents with unilateral pain and ptosis, diplopia, and maintenance of pupillary function. An acute onset of this constellation of symptoms produces a differential with several life threatening conditions with drastically different treatment modalities.

A 56 year old man arrived at the emergency department with unilateral eye pain, blurry vision, dizziness, and headaches. He had a history of hypertension and type 2 diabetes mellitus. Physical exam showed a ‘down and out’ right eye with visual acuity of approximately 20/50, with a normal left eye with 20/40 vision. His HbA1c was measured at 11.1%. One week prior, he was diagnosed with bilateral iritis that prompted dilation with cyclopentolate, inadvertently preventing assessment of pupillary response in the ED. The differential for such a presentation includes diabetic ophthalmoplegia, internal carotid or posterior communicating artery aneurysm, neoplasm, Tolosa Hunt syndrome, and cranial arteritis.

Diagnostic workup involves MR angiogram, CT angiogram, or cerebral angiogram to evaluate for potential aneurysm. The standard of care for this condition is centered on improving glycemic control by increased adherence to diabetes medications. With appropriate glycemic control, complete palsies generally resolve in about 3 months, whereas incomplete palsies last about 2 months.

This case demonstrates a rare complication of uncontrolled diabetes mellitus that requires further work-up due to involvement of the central nervous system. It is important for clinicians to understand the diagnosis of this mononeuropathy, as the presentation of this benign and self-limited disease may belie a more severe and time-sensitive underlying etiology.

DNA-methylation Patterns in Primary Melanomas Indicate Distinct Hypermethylated Phenotype

Nathaniel Slater, Kathleen Conway, Pei Fen Kuan, Sharon N. Edmiston, Nancy E. Thomas

Melanoma is an aggressive malignancy with a high metastatic propensity. DNA methylation, which most frequently occurs at CpG loci in promoter regions, has become increasingly recognized as an important contributor to malignant transformation, and holds promise as a novel target for improvements in diagnosis, monitoring, and treatment of melanoma. High-throughput DNA-methylation array technology has emerged as a sensitive technique for simultaneously evaluating promoter methylation in many cancer-related genes. To date, tumor DNA-methylation studies have been able to distinguish primary melanomas from benign nevi, to uncover novel genes that may be important in melanoma progression, and as a potential prognostic aid. However, it is unclear whether methylation in primary melanomas is associated with tumor progression or defines a subtype. Characterizing the relationship between melanoma methylation patterns and clinicopathologic features could impact selection of methylation biomarkers for diagnostic or prognostic purposes. The present study used the Illumina GoldenGate Cancer Panel I array, which has been previously validated for detecting DNA-methylation in tumors, to evaluate methylation at 1402 CpG sites in 47 primary melanomas. Methylation patterns were examined in relationship to tumor attributes, focusing on tumor features used in American Joint Committee on Cancer (AJCC) staging and somatic BRAF mutational status. On array-wide analysis, methylation levels tended to be higher with increasing Breslow depth and BRAF-positive tumors. In contrast, mitotic rate exhibited an opposite trend with methylation overall, while ulceration was weakly associated with methylation status. On analysis of methylation differences at the 235 most variant loci, K means clustering identified 3 methylation clusters, with one cluster exhibiting distinctly higher methylation across nearly all loci. These clusters differed significantly in Breslow thickness and mitotic rate, with the high-methylation melanoma cluster exhibiting the highest mean Breslow thickness. The observed high-methylation melanoma cluster suggests the existence of a CpG island methylator phenotype (CIMP) in melanoma.

C-Reactive Protein and Erythrocyte Sedimentation Rate as Indicators of the Resolution of Periprosthetic Joint Infection

Christopher P. Lindsay, Daniel J. Del Gaizo, M.D., Christopher W. Olcott, M.D.

Following total joint replacement, periprosthetic joint infection (PJI) can dramatically decrease quality of life for patients. Performing a successful two-stage revision of the infected joint, however, can dramatically improve prognosis. This study aims to evaluate the usefulness of erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels in predicting long-term outcomes of patients following two-stage surgical revision for PJI. To evaluate the utility of these tests, a retrospective cohort study was performed. Participants were recruited from an NC TraCS Institute search of patients who underwent 2-stage revision and re-implantation of the hip or knee joint at UNC Hospitals between July 2004 and July 2012. Twenty-five patients qualified for analysis (16 knees and 9 hips). For each patient selected, ESR and CRP labs drawn prior to the second stage (re-implantation) of the revision, as well as 1 to 5 year follow-up records, were extracted from the charts. For the purposes of this study, ESR values greater than 20 mm/hr and CRP values greater than 1 mg/dL were considered elevated. Recurrence after revision was defined as necessity of additional revisions due to persisting infection OR positive culture on aspiration OR the need for chronic antibiotics to control infection. In both groups, the negative predictive value for recurrence was over 80% for each of four tests: elevation of CRP, elevation of ESR, elevation of both values, and elevation of CRP or ESR. In the knee group, no patient for whom both values were normal suffered a recurrence after revision. These results indicate that when CRP and ESR return to normal prior to the second stage of a two-stage revision, most patients will not experience recurrent infection or require chronic antibiotic maintenance. It seems promising that ESR and CRP could be used as reliable prognostic indicators in two-stage revision of periprosthetic infection.

Intraoperative Round Window Electrocochleography and Speech Perception Outcomes in Pediatric Cochlear Implant Recipients

Eric John Formeister, Douglas C. Fitzpatrick,. Dr. Oliver F. Adunka

Background: Speech perception outcomes following cochlear implantation vary substantially in children. The use of round window electrocochleography (ECoG) at the time of implantation for characterizing hair cell and neural survival shows promise as a quantitative measure of residual cochlear function and as a predictor of speech perception performance.

Methods: ECoG recordings were obtained from 61 children during cochlear implantation. A total power metric was derived from the summed magnitudes of ECoG signals over a frequency series at 90 dB normal hearing level. Implanted children were followed prospectively, and at >12 months postoperatively, children were evaluated with the phonetically balanced kindergarten (PB-k) word list to test open set speech perception. PB-k scores were compared to ECoG power and other clinical covariates using multiple linear regression to construct a parsimonious general linear model for predicting speech outcomes in implanted children.

Results: Total power was weakly and inversely correlated with preoperative audiometric pure tone averages (PTA) (r^2=0.10, p=0.007, n=70). Postoperative PB-k scores were significantly correlated with total ECoG power (r^2=0.30, p=0.005, n=26) and to a lesser extent, with preoperative PTA (r^2=0.18, p=0.04, n=25). After removing patients with significant cognitive deficits and post-lingual hearing loss, the correlation between PB-k scores and ECoG power improved (r^2=0.38, p=0.009, n=17). The addition of PTA, duration of cochlear implant use, age at testing, and age at implantation to the ECoG power did not significantly increase the ability of the model to predict PB-k scores.

Conclusions: Intraoperative ECoG recordings can account for a greater proportion of variance in pediatric speech perception outcomes in prelingually deafened patients than traditionally recognized influences such as mode of communication and educational placement. The relatively weak correlation between total power and PTA and PTA and speech outcomes suggests that the ECoG recordings contain additional information about residual cochlear function than can be determined audiometrically.

Proyecto Puentes de Salud: Disconcordant Weight Perception in Overweight and Obese Mexicans in Rural Guanajuato

Jimmy Chen, Sean Miller, Thayne Dalrymple, Jocelyn Wang, Christina Dean, Melissa Kepke, Yolanda Paylor, Gisselle Mani, Evan Ashkin MD, Sandra Clark MD MPH

Obesity is a growing problem in North America. According to the most recent report by the United Nations Food and Agricultural Organization, the rate of obesity in Mexico is 32.8%, surpassing that of the United States, which stands at 31.8%. Moreover, NHANES data document an obesity rate of 40.4% among Mexican-Americans. A first step in combating obesity among Mexicans in both countries is to gain an understanding of how Mexicans perceive weight.

We asked Mexican citizens living in the state of Guanajuato Mexico several questions about weight perception (for example, whether they considered themselves normal, over-, or under-weight) as part of their participation in health fairs conducted by UNC Chapel-Hill medical faculty and students in 38 rural communities in the spring and summer of 2013. We also collected height, weight, blood pressure and glucose levels at that time.

There were 682 adult participants in the study and 86% were women. Using adult standards developed by the CDC for body mass index (BMI), 41% of participants were overweight and 30.3% were obese. There was a statistically significant difference in participants’ ability to assess their weight: 87% of those with a BMI less than 25 kg/m2 accurately assessed their weight as normal or underweight whereas only 61% of patients with a BMI of greater than 24.9 kg/m2 assessed themselves as overweight or obese (chi squared test, p= <0.001). Furthermore, when presented with drawings of eight persons of varying weight, overweight and obese participants chose diagrams with higher BMIs as their ideal body image compared to normal or under- weight participants (p=0.018).

Overweight and obese Mexicans have altered perceptions of both their own weight and what they consider an ideal weight. Our findings emphasize the need for education about healthy weight as part of any intervention to address obesity in Mexicans and Mexican-Americans.

The Impact of New Born Screening for Cystic Fibrosis on Invasive Proicedures

Manasi Tannu, Marianne Muhlebach

Background/Objective: Newborn screening (NBS) for Cystic Fibrosis (CF) is deemed important in improving CF outcomes because it permits pre-symptomatic diagnosis and earlier treatment initiation. Previously, symptoms of CF had to manifest before diagnostic sweat-testing was performed and often irreversible nutritional and pulmonary morbidities had already occurred. At UNC, bronchoscopies are performed in CF patients presenting with increased respiratory symptoms suggestive of infection. Thus, the number of bronchoscopies performed is an indicator of the number pulmonary exacerbations experienced by young CF patients. The aim of this study was to determine whether CF NBS resulted in fewer bronchoscopies in children at UNC.

Methods: Using a retrospective cohort study, we analyzed the number of CF bronchoscopies using the UNC Pediatric Bronchoscopy database in 4 year intervals from April 2001 until the present. Patients were divided into two groups: patients diagnosed by NBS (patients born after April 2009) and a control group of patients with symptom-based diagnosis of CF (born before April 2009). Since NBS CF patients were born after 2009 and all aged less than 4.5 years at the time of analysis, the control group of CF was age-matched.

Results: The number of bronchoscopies performed on CF patients were 149, 113 and 48 in the time intervals of 2001-2005, 2005-2009, and 2009-2013, respectively. This represents a 58% and 67% decrease in bronchoscopies on NBS-diagnosed patients compared to symptom-based, whereas only a 24% change was observed between the two control periods. The total number of CF and non-CF bronchoscopies was similar throughout these three time intervals.

Conclusions: Early NBS-diagnosis of CF with early initiation of mucus clearance therapies and pancreatic enzyme replacement can lead to less bronchoscopic procedures necessitated. Fewer invasive procedures result in reduced health care costs, potential for complication, and anxiety for parents and patients.

The Effect of Intravitreal Bevacizumab on Macular Edema of Prematurity as Detected by Handheld Spectral Domain Optical Coherence Tomography (SDOCT)

Sailaja Bondalapati, Dr. Michelle Cabrera, Dr. Niklas Ulrich

Retinopathy of prematurity (ROP) is the second leading cause of childhood blindness in the United States. It develops due to insufficient maturation of blood vessels in the retina of premature infants. Between 29% – 60% of infants develop retinal cystoid macular edema (CME) diagnosed by SDOCT but not visible by routine ophthalmoscopy. Our aim is to explore characteristics associated with CME, including response to intravitreal bevacizumab in premature infants screened for ROP. Fifty premature infants undergoing routine screening for ROP underwent imaging with the Envisu R2300 II handheld SDOCT. Images were analyzed using InVivoVue 2.0 software looking for presence of CME. Of the 50 infants, 11 (22%) had CME on SDOCT, of which 8/11 (73%) had ROP. CME was associated with type 1 ROP (p=0.0002), younger gestational age (P=0.0087), higher postmenstrual age at imaging (p=0.0009), and male sex (p=0.0379), however, no significant associations were found for race, birth weight, or ROP zone, stage, or plus status by itself. All five infants (100%) requiring intravitreal bevacizumab for type 1 ROP had CME on OCT compared to 13% (6/45) of infants not requiring treatment (p=0.0002). CME resolved following treatment in two of the five infants, at one and two weeks post-treatment, respectively. CME in a third infant remained stable one week post-treatment. The remaining two infants were recruited after receiving treatment and were found to have CME at the first imaging sessions, which was at eight and 16 weeks post-treatment, respectively. Both infants were discharged soon after and therefore CME status could not be reassessed. This study suggests that the impact of intravitreal bevacizumab on macular edema of prematurity is variable. CME was associated with type 1 ROP, younger gestational age, higher postmenstrual age at imaging, and male sex. The long term visual significance of CME in premature infants is unknown.

β-Globin Sleeping Beauty Transposon Reduces Red Blood Cell Sickling in a Patient-Derived CD34+-Based In Vitro Model

Lucas M. Sjeklocha, Phillip Y.-P. Wong, John D. Belcher, Gregory M. Vercellotti, Clifford J. Steer

Sickle cell anemia (SCA) is a devastating monogenetic illness affecting hundreds of thousands of people worldwide. There are currently limited therapeutic options for patients, and gene therapy is a promising potential treatment for SCA patients. The ultimate goal of gene therapy for sickle cell anemia is an improved phenotype for the patient, but this can be inherently difficult to demonstrate and translate from a mouse model. In this study, we utilized bone marrow from a sickle cell patient as a model of disease in an in vitro setting for the hyperactive Sleeping Beauty transposon gene therapy system. We demonstrated that mature sickle red blood cells containing hemoglobin-S and sickling in response to metabisulfite can be generated in vitro from SCA bone marrow. These cells showed the characteristic morphology and kinetics of hemoglobin-S polymerization, which we quantified using video microscopy and imaging cytometry. Using video assessment, we showed that delivery of an IHK-Beta-T87Q antisickling globin gene by Sleeping Beauty via nucleofection improves metrics of sickling, decreasing percent sickled from 53.2 ± 2.2% to 43.9 ± 2.0%, increasing the median time to sickling from 8.5 to 9.6 min and decreasing the maximum rate of sickling from 2.3 x 10-3 sickling cells/total cells/sec in controls to 1.26 x 10-3 sickling cells/total cells/sec in the IHK-Beta-T87Q-globin group (p < 0.001). Using imaging cytometry, the percentage of elongated sickled cells decreased from 34.8 ± 4.5% to 29.5 ± 3.0% in control versus treated (p < 0.05). These results support the potential use of Sleeping Beauty as a clinical gene therapy vector and provide a useful tool for studying sickle red blood cells in vitro.

Volumetric Reductions of Subcortical Regions of Interest in MDD

Dana Kelley, Jared Minkel, Lisa Ji, Moria Smoski, Gabriel Dichter

Volumetric reductions in the hippocampus, basal ganglia and other reward processing regions have been found to be associated with major depressive disorder (MDD). The most extensive and robust correlations were found for hippocampal reductions. Additionally, more pronounced volumetric alterations have been found to correlate with more severe disease pathology. The ultimate goal of this investigation is to predict individual response to behavioral treatment for MDD. For this portion of the study we had two specific aims, 1) to investigate potential correlations between volumetric characteristics of subcortical grey matter regions and duration of symptoms, 2) to investigate the utility of structural MRI auto-segmentation software for quantitative analysis of clinical data. We hypothesized that we would find volumetric reductions in brain areas associated with reward pathways (hippocampus, basal ganglia, nucleus accumbens, and amygdala) as well as cortical grey matter reductions in patients with MDD and that these findings would correlate with duration of depression. We also hypothesized that greater volumetric reductions would be associated with decreased response to behavioral therapy. We successfully replicated previously demonstrated, robust correlations between reduced hippocampal volume and duration of depression, showing that subjects who had spent more of their lives suffering from depression also tended to have smaller hippocampus volumes than their less depressed counterparts. Additionally we found a negative correlation between volumes of reward pathway regions – namely pallidum/basal ganglia and nucleus accumbens – and duration of depression. Additional parts of this study will explore these subjects response to behavioral activation treatment.

Distinguishing Round Window Electrocochleography Hair Cell from Neural Potentials in a Gerbil Model of High Frequency Sensorineural Hearing Loss

Malika Rakhmankulova, Chris McLaughlin, Douglas Fitzpatrick

In 2004, World Health Organization determined that over 275 million people in the world have moderate-to-profound hearing impairment. Changes in inner ear activity and function remain as one of the major causes of deafness. Cochlear implants are one of the available treatments. Intra-operative electrocochleography (ECOG) has been suggested as one of the possible procedures to assess residual hearing and predict post-operative outcomes. To better understand the signals from hair cells and auditory nerve fibers that add to produce the ECoG, previous studies were done in normal hearing gerbils. To better understand the signal that would be obtained in a candidate for cochlear implantation, the current study used gerbils with noise induced hearing loss (NIHL) to better approximate sloping hearing loss patients (preservation of low frequency hearing, loss of high frequency hearing). Round window ECOGs were obtained pre and post kainic acid treatment (neural excitotoxin), so as to resolve neural from hair cell potentials. It was determined that NIHL ECOG differed from normal hearing ECOG, as shown by the increased number of distortions in the ECOG signal and the relatively larger contribution made by auditory nerve phase locking (auditory nerve neurophonic) to the second and third harmonic distortion. This finding agrees with the general model of ANN distortions as proposed by Forgues, M., et al. (2013), which predicts that nerve carry both an elementary second harmonic distortion due to the nerve rectification, as well as third harmonic distortion under conditions when the nerve signal distribution is narrowed.

Delivery of Therapeutic Wharton’s Jelly Stem Cells on Fibrin Scaffolds for Glioblastoma Multiforme

Guillaume Pegna, Juli R. Bago, Christof Smith, Shawn Hingtgen

Glioblastoma multiforme (GBM) is the most common primary central nervous system malignancy in adults. Current treatment modalities for this disease have proven only marginally effective, with mean survival time after diagnosis of approximately 14 months. As such, more effective treatments are needed. Of particular interest to this lab, 50% of GBMs are sensitive to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) which induces caspase-mediated apoptosis. A secretable form of this cytotoxic agent (S-TRAIL) has been developed by this lab and has been shown to be effective against U87 lineage models of human GBM. As with any GBM chemotherapeutic however, delivery of this agent can be an enormous challenge. Stem cells that have been transformed by a lentivirus to secrete S-TRAIL have tremendous potential in this regard, as they have been shown to have an inherent ability to migrate towards tumor cells. As a delivery system for these stem cells, this lab has tested rapid-assembly fibrin scaffolds, which have previously been approved by the FDA for surgical hemostatic uses in humans. In order to determine the best delivery method for these S-TRAIL transformed Wharton’s Jelly Stem Cells (WJSCs), we tested different ways of loading the WJSCs onto the fibrin scaffolds. Four groups with equal initial quantities of WJSCs were tested in vitro for WJSC survival, migration, scaffold degradation, and S-TRAIL secretion: non-flattened “drops†of fibrin with WJSC encased within, flattened “drops†of fibrin with WJSC encased within, flattened “drops†of fibrin with WJSC encased within and placed on the exterior surfaces, and flattened “drops†of fibrin with WJSC placed only on the exterior surfaces. These initial studies have demonstrated that the group with WJSC placed only on the exterior surfaces demonstrate good WJSC survival and migration and higher S-TRAIL secretion and slower scaffold degradation than the other groups.

The incidence of neoplastic gastric cardia nodules following radiofrequency ablation of neoplastic Barrett’s esophagus

Cotton CC, Wolf W, Pasricha S, Li N, Hathorn K, Madanick RD, Dellon ES, Spacek MB, Moist SB, Shaheen NJ

Introduction: Radiofrequency ablation (RFA) is safe and effective for the eradication of dysplastic Barrett’s esophagus (BE). Following RFA, nodular neoplasia may occur in the gastric cardia.

Methods: We conducted a retrospective cohort study of patients who underwent RFA for BE at the UNC Hospitals between 2006 and 2013. Neoplastic gastric nodules were defined as any raised area at or distal to the top of the gastric folds (TGF) with histology of LGD, HGD, or IMC, or invasive adenocarcinoma. The gastric cardia was defined as extending from the TGF to 3 cm distal to TGF. Patients were excluded for non-dysplastic BE, prior treatment of BE with other modalities, and familial adenomatous polyposis. Bivariate analyses used Fisher’s exact test and survival analysis used the product-limit method.

Results: Of 299 patients receiving RFA, 284 met the inclusion criteria. During 589 person-years of follow-up, 19 nodules arose in the gastric cardia; all were submitted for histology. Eight neoplastic nodules of the cardia arose (42% of all nodules, 3% of patients), an incidence rate of 2.3% per person-year. All were completely excised with EMR. In bivariate analysis, development of nodular cardiac neoplasia exhibited borderline associations with advanced age (75 vs. 68, p = 0.07) and elevated BMI (33.8 vs. 29.7, p = 0.06).

Discussion: Most nodules arising in the cardia after RFA are benign, and the incidence of neoplastic cardia nodules following RFA was low. However, 3% of patients did develop neoplastic cardia nodules. Close endoscopic evaluation of the cardia is warranted after RFA for neoplastic BE and raised lesions should be excised.

Manual liquid-based cytology: A pilot study

Lisa Rahangdale, MD, MPH, Debra Budwit, MD; Davoud Asgari, PhD ; Linda Ohadugha, BS

Introduction: Automated liquid-based cytology methods for cervical cancer screening require processing systems that may not be affordable in low resource settings. The purpose of this study was to assess the utility of the manual liquid-based cytology product VitroPrepâ„¢ Gyn/Cytology Processing Kit (chemQ bioscience, LLC, RTP, NC).

Methods: This is a descriptive pilot study. Women underwent cervical sampling to be processed by the Thin Prep liquid-based cytology system. This was followed by cervical sampling for the VitroPrep system. All samples were evaluated by a single blinded gynecologic pathologist. Results were scored as follows: 1=unsatisfactory, 2=borderline, 3=acceptable, 4=good, 5=excellent. These criteria were assessed: monolayer cell adhesion, overall cellularity, background clarity, preservation of cellular morphology, red cell lysis, and elimination of mucus/debris. Specimens were evaluated for adequacy based on Bethesda criteria and diagnosis was compared to results from Thin Prepâ„¢. Additional women were sampled prior to conization procedures.

Results: Forty-seven women underwent dual cytologic sampling. Five manual samples were unsatisfactory due to low cellularity and excluded. All scores were 3-5 with >90% graded 4-5. The VitroPrep diagnosis correlated with the Thin Prep diagnosis 90% (38/42). All Vitroprep specimens obtained from 15 additional women prior to conization were satisfactory and correlated abnormal cytologic findings with CIN 1-3 pathology.

Conclusions: Despite the disadvantage of obtaining samples after an initial cytologic or biopsy sample, VitroPrep was able to provide adequate specimens for evaluation and diagnosis. This low cost processing method may provide a useful alternative in settings where automated liquid-based cytology systems may not be feasible.

Is it really a UTI? How Useful REALLY Are Clinical Signs in Older Persons?

Kaleb Keyserling; Anna Beeber, PhD, RN; Phillip Sloane, MD

Background: Urinary Tract Infections (UTIs) are the most commonly diagnosed infection in long-term care facilities, and antibiotics are prescribed at a rate that many consider inappropriately high. Diagnostic criteria have been accepted by many national organizations as the standard of care for diagnosing UTIs; however, much uncertainty and disagreement remains among health care professionals about how to diagnose a UTI. Particularly common are disagreements about whether and to what extent certain nonspecific signs and symptoms, such as change in urine odor, confusion, or agitation, are indicative of a UTI. To address these issues, we reviewed the scientific literature, with a focus on common clinical questions.

Methods: A PubMed search was performed to evaluate specific clinical findings in nursing home residents and their association with UTIs. Data were compiled to determine which signs/symptoms are the best markers for UTIs. A second search was done to evaluate current diagnostic criteria for UTIs including their ability to detect UTIs and decrease the number of antibiotics prescribed.

Results: Fever, changes in urine characteristics, and several nonspecific symptoms may be associated with bacteriuria but are not specific to UTIs. In addition, UTI diagnostic criteria have been shown to decrease antibiotic use, but may not be particular sensitive in identifying UTIs.

Conclusions: Research suggests that mental status changes and variations in the character of urine (such as odor) are less specific to urinary tract infections than is commonly believed. It is clear that more research is needed in determining what signs/symptoms are actually associated with UTIs and to determine a more clinically valid marker for UTIs than bacteriuria. A further large-scale randomized evaluation of current UTI diagnostic algorithms is needed to determine if they effectively decrease antibiotic use.

Evaluation of Community Bridges to Cancer Clinical Trials: a faith-based intervention for increasing African American awareness of cancer clinical trials

Pranay Prabhakar, Melissa Green, Adebowale Odulana, Malika Roman Isler, Michelle Hayes, Mimi Kim, Margo Michaels, Natasha Blakeley, Giselle Corbie-Smith

Background: Cancer morbidity and mortality disproportionately burdens African American (AA) communities, and yet AAs remain underrepresented in cancer clinical trials (CCT). To understand etiologies of disparate outcomes and address issues of social justice and generalizability of results, representation of AAs in CCTs is imperative. Assessing and improving knowledge, advocacy, and comfort with discussing CCTs is an important step in increasing trial diversity. The Community Bridges (CB) intervention is a structured workshop delivered by members of faith communities that focuses specifically on cancer clinical trials and uses a presentation and role-play format. Objective: We evaluated and compared the efficacy of CB in improving three domains of competency—knowledge, advocacy, and comfort—with discussing CCTs versus a comparison intervention that focused on other health advocacy topics (advance care planning and tissue/organ donation). Methods: Individuals from 8 churches from various NC counties were trained to deliver either CB or the comparison workshops at their respective churches. We obtained baseline, post-test and one-month follow-up responses to 12 survey questions, assessing the three aforementioned domains, from workshop participants (CB (n=145) and comparison (n=119)). Data was analyzed using JMP10.0 (SAS). Results: Compared to participants in the comparison intervention, participants in CB showed greater improvement in all three domains adjusted for age and gender (p<0.01) suggesting that the structured, interactive, and focused content and delivery of CB made a positive impact. However, domain-level improvements were attenuated at one-month follow-up. Topic-specific analyses revealed specific strengths (e.g., a 1.4 to 2 fold greater increase in comfort level with discussing CCTs with others versus the comparison group) and areas that need improvement (e.g., knowledge about placebos). Conclusion: Targeted faith-based delivery of CB showed promise in improving knowledge, advocacy, and comfort level regarding CCTs in AA communities and with a few improvements may serve as a model program for implementation in similar communities across the US.

Fingertip dermatitis of unknown etiology: Response to systemic therapies

Patrick O’Shea, Aida Lugo-Somolinos MD

Background: There is no consensus about the classification or treatment of hand dermatitis. The clinical picture can be shared by several etiologies, so diagnosis and treatment is often difficult and frustrating both to the patient and the dermatologist. Recent studies have produced treatment algorithms for hand dermatitis, but there are no current indications of systemic treatments for chronic hand dermatitis.

Objective: To evaluate the response of hand dermatitis with fingertip involvement to systemic treatments.

Methods: A chart-retrospective review of all patients with hand dermatitis seen at the University of North Carolina Dermatology and Skin Cancer Center from September 2007 to April 2013.

Results: Eighty-three hand dermatitis charts were reviewed. Twenty-seven had hand dermatitis with fingertip involvement. Thirteen of these patients were treated with acitretin and/or methotrexate. At 6 months, acitretin achieved clearance/almost clearance in 50% (4 of 8) of patients, compared to 0% (0 of 8) treated with methotrexate. Three patients were treated with both acitretin and methotrexate.

Conclusion: Systemic retinoids are a good alternative for the treatment of hand dermatitis with fingertip involvement.

The Development and Feasibility of an Electronic Decision-Support Tool in Treating Pediatric Obesity

Megan Campbell, Sarah Armstrong MD, Eliana Perrin MD, MPH

Despite the prevalence of pediatric obesity and national recommendations urging physicians to counsel patients at-risk, provider self-efficacy regarding pediatric obesity counseling remains suboptimal. This study aimed to develop and assess the feasibility of an electronic-decision support tool, MeTree Jr., and to evaluate its ability to increase Motivational Interviewing (MI) fidelity and obesity knowledge of providers, improving provider self-efficacy. We are developing MeTree Jr to be evidence-based, gather information from patients, and provide recommendations to providers in real time. It will facilitate counseling by incorporating the principles of MI to promote behavior change. The tool will be evaluated with pre- and post- tool questionnaires and structured observations assessing MI. The pre-tool questionnaire was administered to physicians within an academic-setting pediatric clinic, with the goal of acquiring a baseline for MI knowledge, familiarity with evidence-based measures promoting healthy lifestyles among children and provider self-efficacy. These providers will use the tool for one month and complete a post-test questionnaire.In pretesting, provider confidence for counseling to increase healthy eating behaviorsand identifying inadequate physical activity each had 29% of providers feeling less than confident. Confidence was also less than optimal for counseling to increase physical activity and calculating BMI in children with 21% feeling less than confident. Provider comfort with MI was also less than optimal with 46% feeling neither comfortable nor uncomfortable and 15% feeling uncomfortable or not comfortable at all. From this pre-testing, it is hoped that the interactive, web-based decision-support tool, MeTree Jr. will improve provider self-efficacy through increasing confidence and MI comfort among providers.

Provision of a clean water supply and diagnostic lab equipment to a rural health center in the Democratic Republic of Congo and its utility in the diagnosis of infectious diarrhea

Claire Hailey, Melissa Bauserman, Justin Gado, Carl Bose

“Purpose

In low-income countries (LICs), lack of clean water sources and deficits in healthcare delivery result in poor health outcomes. These health centers may gain significant benefits from donations. However, the donations can be impractical substitutes for technologies that are truly needed. The purpose of this project is to evaluate the utility and durability of healthcare equipment and supplies donated to a rural health center and to improve the capacity to diagnose intestinal pathogens common in the Democratic Republic of Congo (DRC).

Methods

We assembled a set of supplies to donate, including physical diagnostic equipment, non-invasive instrument tests, and laboratory supplies. We provided facility upgrades, including restoration of the fresh water supply. For one year, we collected information on equipment usage for each patient encounter. Quarterly we surveyed the functionality of the instruments.

Results

The five most commonly utilized physical diagnostic equipment items are typically used in obtaining vital signs. The non-invasive instrument tests (pulse oximetry and blood glucose) were infrequently utilized. The most commonly used diagnostic laboratory tests (blood smear for malaria and stool analysis) reflect the prevalence of diseases in the region. Nearly all of the donated instruments were available and functional for the entire assessment period.

Conclusion

This study adds valuable information about the utility and durability of equipment supplied to a health center in the DRC. We presume that better equipment will improve diagnostic ability, thereby improving treatment and outcome. Information from this pilot study can be used to determine the appropriateness of donated medical equipment in similar settings.”

Oil the Wheel that Doesn’t Squeak: The Underappreciated Importance of Passive Behavioral Symptoms in People with Dementia

Christopher Schifeling; Philip D. Sloane, MD, MPH; Anna Beeber, PhD, RN

BACKGROUND: Passive psychomotor symptoms, such as weakness and inactivity, and active psychomotor symptoms, such as agitation and aggression, are both common in people with dementia. The purpose of this study was to review caregiver resources and academic literature on passive and active psychomotor symptoms in dementia to guide the development of internet-based resources for caregivers.

METHODS: Three national websites for dementia (Alzheimer’s Association, Alzheimer’s Society and Alzheimer’s Australia) were reviewed for pages devoted to passive and active psychomotor symptoms. Journal articles were searched through PubMed using the search terms dementia in combination with passivity, apathy, inactivity, agitation, aggression and wandering.

RESULTS: Several studies showed that passive symptoms are more predictive of acute illness than active symptoms. All three national websites for caregivers we analyzed had pages specifically devoted to active symptoms but none had pages specifically devoted to passive symptoms. Likewise, searching PubMed found five validated scales for measuring active psychomotor symptoms but no validated scales were found for measuring passive psychomotor symptoms.

CONCLUSION: While passive psychomotor symptoms are more predictive of acute illness than active psychomotor symptoms, the former have received much less attention than the latter in both resources for caregivers and in academic journal articles. More attention needs to be given to passive psychomotor symptoms in scientific research and in the education of caregivers.

Optimizing Decellularized Porcine Maxillary Bone as a Scaffold for Novel Autologous Stem Cell Treatments

Justin Morse, Alexandra Halevi, Montserrat Caballero, Amita Shah, Jeyhan Wood, John van Aalst

Introduction: Our lab has previously demonstrated bone generation with autologous stem cell treatments in a surgically created maxillary cleft model in juvenile swine. However, our current nano- scaffolds are < 1mm thick and do not provide the volume to fill the surgically created cleft. Decellularized bone as a scaffold may provide a solution because it provides volume and retains matrix proteoglycans with growth factors to provide a roadmap for bone regeneration. The aim of this work is to optimize a protocol for decellularization of adult swine maxillary bone and examine in vitro MSC growth on these scaffolds.

Methods: Bilateral maxillae were harvested from 3 fresh adult swine heads. Decellularization was performed using an enzymatic protocol (phospholipase A2 (36u/L) with 4.2M salt washes) with agitation or sonication. A single piece of maxilla was fixed in 10% PFA as a control. Samples were cryosectioned in 5µM sections and stained with H&E. Mean percent of sample decellularized was calculated using the average nuclear remnants visible in 5 high power fields. Six additional pieces of maxilla were decellularized with sonication. Umbilical cord (UC) MSCs were grown to confluence in standard MSC growth media, transduced with lentivirus expressing GFP, and seeded onto decellularized maxillae. Cell attachment and proliferation was examined by immunofluorescent microscopy at days 3 and 7.

Results: The superior maxilla of the porcine facial skeleton offers the best cancellous bone for decellularization. Agitation resulted in 21.30% (SD 15.28) of sample decellularized, while sonication resulted in 43.35% (SD 10.23) standardized to control. Fluorescent microscopy demonstrated attachment and proliferation of UC MSCs expressing GFP on decellularized samples after day 3.

Conclusion: Sonication results in improved bone decellularization. MSCs attach and proliferate on these maxillary scaffolds suggesting that they will be suitable for in vivo testing in our swine model.

Data fidelity in the database migration and documentation of the clinical care of prehospital patients

Andrew T. Hnat, Jane Brice

Background: The EMS Agenda for the Future stressed the need for Emergency Medical Services (EMS) to be fully recognized as a member of the overall healthcare system. Such a partnership will require the transmission and integration of data. The North Carolina Office of EMS has developed and implemented the Prehospital Medical Information System (PreMIS). Every EMS system in North Carolina is required to transmit a patient care report for every EMS response within 24 hours. This study aimed to determine the data fidelity in the data collection and transmission process to assess for data loss within the process of patient evaluation, documentation by EMS staff, and data migration to the PreMIS system.

Methods: EMS personnel from two North Carolina counties completed scripted and observed patient care simulations. Three potential data loss points were assessed. Data acquisition during the scenario was assessed by a trained observer. Documentation accuracy of those scenarios was recorded by review of the documented patient care report within the EMS systems’ software package. Finally, the patient care reports were allowed to migrate to the state database where they were again assessed for consistency.

Results: A total of 107 simulations were observed. During data acquisition, EMS staff failed to obtain 15.1% of the data points being tracked. Of those data points that were obtained, 86.5% were correctly documented in the patient care report. Between the counties’ systems and the PreMIS database, 4.7% of patient care reports (PCRs) were lost. Additionally, of the data that did migrate correctly, 15.5% of the data points at the state level were incorrect compared with the county documentation.

Conclusions: Significant data loss occurs between patient assessment and data deposition within the state EMS database. We strongly urge PreMIS database staff to locate the sources of data loss and to ensure data fields, including optional or case-specific fields, are being completely imported from each county.

Mindfully Targeting Burnout: An Open-Label Trial of a Mindfulness-based Curriculum for Psychiatry Residents

Jonny Gerkin, MD; Jason Tatreau, MD; Kenan Penaskovic, MD; Rushil Patel, MSIII; Anna Brandon, PhD, ABBP.

Even after the implementation of ACGME work-hour regulations, psychiatry residents continue to report burnout. Mindfulness-Based Stress Reduction (MBSR) has been shown to effectively reduce psychological distress among physicians, but the time commitment (8 weekly, 150-minute sessions, day-long retreat) appears impractical for resident physicians. This pilot study is designed to assess the acceptability and feasibility of a novel mindfulness-based curriculum, Mindfully Targeting Burnout Curriculum (MTBC), while examining its effects on symptoms of burnout in a cohort of psychiatry residents. The curriculum was integrated into didactics for senior psychiatry residents. Participants (n=15) were exposed to 8 weekly, 45-minute sessions adapted from MBSR-based, Mindfulness Based Cognitive Therapy. Survey responses and other measures indicate the curriculum was acceptable and feasible. Of the 14 participants who completed these surveys, 11 felt the curriculum to be valuable to their self-care, and 9 incorporated mindfulness practices upon completion. The mean number of sessions attended was 6.4. Secondary measures, the Mindfulness Attention Awareness Scale (MAAS) and Maslach Burnout Inventory (MBI), were administered, and scores were compared using a paired t-test. Means of pre- and post-curriculum MAAS scores differed by -2.36 (p=0.3554). Differences between the means for pre- and post-MBI scores were computed for three dimensions Personal Accomplishment (PA), Emotional Exhaustion (EE), and Depersonalization (DP) which were 11.64 (p<0.0001), 7.71 (p=0.002), and 5.73 (p=0.0004), respectively. An increase in the PA score corresponded with decreased burnout whereas increases in EE and DP did not. There was no statistically significant change in the MAAS score. These inconsistencies can be explained by study limitations, such as small and heterogeneous sample, lack of randomization or control, time-intensive nature of some of the interventions, mandatory curriculum and test-retest biases. A randomized and controlled study with a larger cohort composed of a less heterogeneous, voluntary group of learners may demonstrate other findings.

The Effect of a Lactation Counseling Program on Rates of Early and Exclusive Breastfeeding Initiation in a Public Institutional Delivery Setting in Jammu, India

Shivani Sud

Early and Exclusive Breastfeeding Initiation (EEBI), within the first day or optimally first hour following birth, reduces neonatal mortality and morbidity. First milk, colostrum, possesses immunologic and nutritious properties. In India and Pakistan only 24%–26% of newborns are breastfed within the first hour. We implemented a breastfeeding initiation program that draws upon cognitive behavioral therapy (CBT) elements to promote EEBI. We conducted a randomized trial on the effect of this lactation counseling program on EEBI in a public hospital in Jammu City, India. Mother-neonate dyads were enrolled (n=204) and placed in intervention (n=102) or control (n=102) groups. All mothers expressed intention to breastfeed (n=204). Approximately 20% of mothers believed colostrum should be discarded. Within the control group, timing of breastfeeding initiation correlated with method of delivery. Women were most likely to initiate 2 and 3 days after birth for vaginal and cesarean delivery, respectively. The first hour initiation rate was negligible independent of delivery method. Mothers most frequently cited the following barriers to EEBI: painful stitches, belief that milk is not present or formula is superior to breast milk, and lack of breastfeeding knowledge. Within the intervention group, 90% of women accepted immediate intervention to initiate breastfeeding including latch assistance and all participants accepted verbal counseling. Between 75-85% of intervention participants breastfed exclusively during their inpatient stay. Mothers utilizing formula cited concerns regarding inadequate milk supply. Between 25-40% of mothers offered the breast at least 8 times per day as instructed. However, nearly 95% of mothers increased feeding frequency and 95% awoke at night to breastfeed as recommended. The high acceptability and compliance with this intervention program delivered by non-physician personnel who received moderate training suggests the CBT-based intervention presented here is a high impact program adaptable to other institutional delivery settings.

Diffuse Leptomeningeal Oligodendroglioma

Brice Kessler, Yueh Lee

This case report reviews the presentation and pathology of diffuse leptomeningeal oligodendrogliomatosis with a focus on imaging. This rare tumor predominately affects pediatric patients and can present with a variety of neurologic symptoms. Of great concern is the nonspecific appearance of diffuse leptomeningeal uptake on early MRI. This case describes a 12 year old patient who presented with new onset non-localizing neurologic symptoms with diffuse leptomeningeal enhancement. Ultimately two biopsies were necessary to arrive at the diagnosis of primary leptomeningeal oligodendroglioma. The patient’s indolent disease course is reviewed and postmortem histology is shown to demonstrate anaplastic transformation and invasion and serve as a correlate to imaging. The literature on this rare pathology is also reviewed with an emphasis on current diagnosis and treatment protocols.

Etiologies of Altered Mental Status: a retrospective observational cohort of patients presenting to the adult medical ward at Kamuzu Central Hospital, Lilongwe, Malawi

Bryna Harrington, Charles Kyriakos Vorkas, Cecilia Kanyama, Irving Hoffman, Mina Hosseinipour

Altered mental status (AMS) is a common symptom among patients presenting to acute health care settings and has a wide spectrum of etiologies. Little is known about causes of AMS in patients in resource-limited setting (RLS) hospitals. We evaluated etiologies of AMS among patients admitted to the adult medical wards at Kamuzu Central Hospital in Malawi from April 15 through May 31, 2013 through a retrospective observational cohort study. Inclusion criteria required having one of the following: (1) a Glasgow Coma Score <15; (2) a chart containing any one of the AMS key words: confused, drowsy, delirious, disoriented, convulsing, unconscious, or comatose; OR (3) a lumbar puncture (LP) indicated in the diagnostic plan. Of the 643 adult admissions during the study period, 546 charts were located, with 170 (31%) patients meeting inclusion criteria (49% female, median age 38, HIV status: positive 48%, negative 29%, unknown 23%). 92 (54%) had a Glasgow Coma score recorded, of which 62 (67%) had a score <15. 117 (68%) were described with a key AMS term, and 114 (67%) were assigned to receive an LP with 72 (63%) LPs successfully completed. The most common diagnoses in patients with AMS were infectious (66%), including malaria (21%), meningitis (bacterial 11%, cryptococcal 6%), and sepsis of unknown source (14%); bacterial meningitis carried higher mortality (69%). Non-infectious etiologies included diabetic ketoacidosis (2%), kidney injury (4%), seizures (8%), and stroke (10%); kidney injury carried higher mortality (83%). 40% of patients meeting inclusion criteria for AMS or receiving an LP died. Of the patients who died, 55% were HIV+, 19% HIV-, and 26% had unknown HIV status. In conclusion, AMS carries significant mortality. The majority of AMS cases had infectious diagnoses, yet a substantial portion was associated with non-infectious illnesses. Attention to clinical management of these conditions in RLS is needed.

The mucosal tissue metabolome is altered in obesity

Nugent, Julia; McCoy, Amber; Sandler, Robert; Keku, Temitope

Obesity is a complex, multifactorial disease that is associated with significant increased risk of development of life-threatening and debilitating secondary disorders. Studies have linked an altered microbiome with obesity, yet the functional implications of gut bacterial dysbiosis remain unclear. Gut bacteria contribute to nutrient metabolism and produce small molecules termed the “metabolome,†which is the ultimate physiological response of biological systems to genetic or environmental changes and may contribute to the development of many diseases.

To determine if the metabolome was altered in obesity, we assessed the metabolome in rectal mucosal biopsies of 19 overweight subjects (body mass index ≥ 25 kg/m2) and 8 normal weight controls (body mass index between 18.5 kg/m2 and 24.9 kg/m2) by liquid and gas chromatography time-of-flight spectrometry. Study participants were from the Diet and Health Study V, a study on colorectal adenomas, in which persons age 30 years or older who had normal screening colonoscopy at the University of North Carolina Hospitals (Chapel Hill, NC). For this study, participants were randomly selected from the subjects confirmed to have no colorectal adenomas or cancer. Cases (overweight subjects) and controls (normal weight subjects) were comparable for general characteristics. We identified a total of 264 metabolites in rectal mucosal biopsies. Cluster analysis suggested a separation of metabolomic profiles between overweight cases and normal weight controls. Ten metabolites were significantly different between cases and controls, notably a decrease in overweight cases of the antioxidant alpha-tocopherol (vitamin E; fold change -3.13, p-value 0.0280) and an increase of the bile acid metabolite deoxycholate (fold change 2.28, p-value 0.0754). Previously studies have shown that alpha-tocopherol and deoxycholate play a role in oxidative stress and inflammation, both of which are associated with obesity. Taken together, these findings suggest that metabolic products and an altered metabolome may contribute to the development of obesity.

Study of the Role of Transcription Factor MIST1 in Paneth Cells

Deepak Ravindranathan

Doxorubicin (dox), a commonly used chemotherapeutic drug, has often been associated with damaging the intestinal epithelium causing various side effects such as nausea, vomiting, diarrhea, and malabsorption, which can present potential dose limiting complications. Currently, there are no effective means of minimizing these side effects; the symptoms can only be managed. Dekaney et al. reported that dox induces mucosal damage in mice including loss of intestinal stem cells (ISC); however, concomitantly, significant expansion in Paneth cells (PC) compartment was observed resulting in increases in PC number, granule number, granule size, and secretory capacity. However, the factors involved in this phenomenon are not well understood. This project focused on the role of the transcription factor, MIST1, which has been shown to play a role in secretory function in a variety of exocrine cells such as PCs. As MIST1 is a scaling factor, we anticipated that MIST1 controls the PC secretory capacity in both normal homeostasis and during intestinal epithelial repair following Dox-induced damage. In an effort to begin examining the function of this protein, its respective knockout mice, MIST1-/- were generated. Deleting MIST1 did not seemingly affect the structural integrity of the crypts while in vitro crypt cultures suggest that loss of MIST1 did not impair the ability to affect the crypt budding process. However, histological analysis of the intestinal tissue of a MIST1-/- mice after doxorubicin treatment interestingly shows loss of a majority of crypts, which suggests that this transcription factor may play a role under disturbed conditions. Further investigation is necessary to elucidate the exact role of this transcription factor.

Cochlear nerve contribution to the electrocochleography (ECoG) signal

Chris McLaughlin, Malika Rakhmankulova, Doug Fitzpatrick

Electrocochleography (ECoG) is an important technique used to record the electrical potentials of the inner ear in response to stimuli. This technique is used intraoperatively to examine the health of the cochlea, specifically for the identification of endolymphatic hydrops in patients with Meniere’s disease, in addition to the diagnosis of auditory neuropathy. Moreover, ECoG is currently being used here at UNC during Cochlear Implantation (CI) to assess the integrity of the cochlea before surgery and to reduce cochlear trauma caused during electrode placement. Our project involved studying ECoG potentials from the round window of gerbils with noise induced hearing loss (NIHL). These gerbils provide a hearing model for many cochlear implant patients, with significant hearing loss at high frequencies, with some residual hearing at lower frequencies. The application of kainic acid at the round window was used to eliminate neural potentials from the ECoG signal. It was determined that NIHL ECoG differed from normal hearing ECoG by larger summating potentials with increased contribution from auditory nerve, which disagrees with the generally established model of pure inner hair cell contribution to the summating potential. This agrees with the proposed model by Forgues, M., et al., which suggests that nerves contribute to summating potential in normal hearing gerbils, but are made more obvious with the destruction of additional hair cells in cochlea. This general trend also agrees with some intra-operative recordings done in humans, which show increased summating potential in patients with damaged auditory nerve.A greater understanding of the ECoG signal during intraoperative recordings may provide better outcomes for patients receiving CI surgery.

Viability of Chondrocytes after In Vivo Injection of Local Anesthetic and/or Corticosteroid

Michael Sola, Dr. Laurence Dahners, Dr. David Flood, Dr. Paul Weinhold, Stephen Kallianos

Background: Injections of corticosteroids and/or anesthetics are frequently used in clinical settings to decrease inflammation and pain. However, there are many in vitro studies showing that these substances are toxic to chondrocytes. This in vivo study was performed to determine whether common clinical injections are as toxic as described in vitro.

Methods: The left knees of Sprague-Dawley rats were injected with 0.03mL of either saline, 0.5% bupivacaine with 4mg/mL methylprednisolone, or pH balanced 0.2% or 0.5% ropivacaine, or preservative free 1mg/ml or 4mg/mL triamcinolone acetonide, or a combination of pH balanced 0.2% ropivacaine and preservative free 1mg/mL triamcinolone acetonide, or a combination of pH balanced 0.5% ropivacaine and preservative free 4mg/ml triamcinolone acetonide. The rats were sacrificed after one week and live/dead staining was performed on the cartilage of the knees. Confocal microscopy and image processing was used to quantify the number of live and dead cells within each sample.

Results: All injections (even saline) excepting pH balanced 0.2% ropivacaine combined with preservative free 1mg/mL triamcinolone acetonide resulted in significant decreases in chondrocyte viability (P<0.05). We did not detect a significant difference in viability between 0.2% and 0.5% ropivacaine but the 4mg/mL concentration of triamcinolone did result in lower viability than the 1mg/mL concentration (P=0.038). The viability of the combination of 0.2% ropivacaine combined with 1mg/ml triamcinolone acetonide was significantly higher than the individual injections of each of the other solutions (P<0.05).

Conclusions: At 0.2% and 0.5% concentrations, pH balanced ropivacaine solutions were similarly toxic to chondrocytes. The lower concentration combination (0.2% ropivacaine and 1mg/ml triamcinolone acetonide) was less toxic than individual injections of ropivacaine and triamcinolone acetonide and was significantly less toxic than all of the other injections except saline (P<0.05).

Patient Expectations and Perceptions of Endoscopic Skull Base Surgery

Yemeng Lu, Candace Mitchell, Adam Zanation

Background:

In recent years, the endoscopic approach has become the increasingly utilized surgical approach for many skull base pathologies. While the safety and efficacy of this approach have been demonstrated, little is known regarding patients’ understanding of the procedure and their expected post-operative course prior to undergoing these surgeries

Objective:

In order to provide more effective guidance and consent to future patients, the authors of this study aim to understand the expectations that patients have regarding endoscopic skull base surgery.

Methods:

Subjects are 21 adult patients who underwent endoscopic skull base procedures for a variety of relevant pathologies. They were enrolled in an IRB approved study in their post operative period after complete healing (>4 months). Qualitative research methodology in forms of a survey was used to assess expectations and experiences regarding the surgery, the risks associated, and the post-operative course. The survey was administered to a cohort of patients (21 subjects) consists of post-operative patients who have undergone endoscopic skull base surgery and who are returning to clinic for follow-up.

Results:

Patients were asked to compare their outcome results and risks to their pre-operative expectations. They expressed somewhat less operative time, length of hospitalization, pain, and cosmetic adverse effect. For time to recovery and sinus function, they experienced similar outcomes compared to expected, but for effect on ability to smell, their experiences was somewhat more than expected. In terms of expectations of risks of surgery including stroke, bleeding, vision changes, brain damage, CSF leak, meningitis, infection and overall operative risk, their post-operative perceptions were somewhat less than expectations prior to surgery. When stratified by tumor malignancy, the patients with malignant tumors perceived more effect on cosmesis (p=0.05), increased risk of stroke (p=0.04) and vision damage (p=0.08) compared to those without malignant tumors. Patients who have had previous skull base surgeries also perceived increased risk of infection (p=0.06) compared to those without prior surgeries. Free response comments from these patients revealed a generally positive perception and experience with the endoscopic skull base procedures.

Conclusion:

This is a pilot study to gain a qualitative understanding of the patients’ experiences and perceptions about their endoscopic skull base surgery. Overall, patients reported less outcome dysfunctions and risk for complications compared to their pre-operative expectations. However, some patients perceived similar to more negative effect on their ability to smell after their operation. Results of this study have potential benefit for future patients; they can be incorporated into the informed consent for future endoscopic procedures, thus more effectively aligning patient expectations with patient experience.