Cytoplasmic HuR Status Predicts Disease-free Survival in Resected Pancreatic Cancer: A Post-hoc Analysis From the International Phase III ESPAC-3 Clinical Trial.

OBJECTIVES: We tested cytoplasmic HuR (cHuR) as a predictive marker for response to chemotherapy by examining tumor samples from the international European Study Group of Pancreatic Cancer-3 trial, in which patients with resected pancreatic ductal adenocarcinoma (PDA) received either gemcitabine (GEM) or 5-fluorouracil (5-FU) adjuvant monotherapy. BACKGROUND: Previous studies have implicated the mRNA-binding protein, HuR (ELAVL1), as a predictive marker for PDA treatment response in the adjuvant setting. These studies were, however, based on small cohorts of patients outside of a clinical trial, or a clinical trial in which patients received multimodality therapy with concomitant radiation. METHODS: Tissue samples from 379 patients with PDA enrolled in the European Study Group of Pancreatic Cancer-3 trial were immunolabeled with an anti-HuR antibody and scored for cHuR expression. Patients were dichotomized into groups of high versus low cHuR expression. RESULTS: There was no association between cHuR expression and prognosis in the overall cohort [disease-free survival (DFS), P = 0.44; overall survival, P = 0.41). Median DFS for patients with high cHuR was significantly greater for patients treated with 5-FU compared to GEM [20.1 months, confidence interval (CI): 8.3-36.4 vs 10.9 months, CI: 7.5-14.2; P = 0.04]. Median DFS was similar between the treatment arms in patients with low cHuR (5-FU, 12.8 months, CI: 10.6-14.6 vs GEM, 12.9 months, CI: 11.2-15.4). CONCLUSIONS: Patients with high cHuR-expressing tumors may benefit from 5-FU-based adjuvant therapy as compared to GEM, whereas those patients with low cHuR appear to have no survival advantage with GEM compared with 5-FU. Further studies are needed to validate HuR as a biomarker in both future monotherapy and multiagent regimens.

GABAergic synaptic plasticity during a developmentally regulated sleep-like state in C. elegans.

Approximately one-fourth of the neurons in Caenorhabditis elegans adults are born during larval development, indicating tremendous plasticity in larval nervous system structure. Larval development shows cyclical expression of sleep-like quiescent behavior during lethargus periods, which occur at larval stage transitions. We studied plasticity at the neuromuscular junction during lethargus using the acetylcholinesterase inhibitor aldicarb. The rate of animal contraction when exposed to aldicarb is controlled by the balance between excitatory cholinergic and inhibitory GABAergic input on the muscle. During lethargus, there is an accelerated rate of contraction on aldicarb. Mutant analysis and optogenetic studies reveal that GABAergic synaptic transmission is reduced during lethargus. Worms in lethargus show partial resistance to GABA(A) receptor agonists, indicating that postsynaptic mechanisms contribute to lethargus-dependent plasticity. Using genetic manipulations that separate the quiescent state from the developmental stage, we show that the synaptic plasticity is dependent on developmental time and not on the behavioral state of the animal. We propose that the synaptic plasticity regulated by a developmental clock in C. elegans is analogous to synaptic plasticity regulated by the circadian clock in other species.

New Model for Osteoporosis Risk Screening Using Emergency Department Visits.

Background Even though osteoporosis is the most common bone disease in the United States, it is frequently underscreened and underdiagnosed. In this study, we aimed to utilize the Emergency Department to conduct preemptive osteoporosis risk screening and assess the risk associated with gender and race based on a statistical analysis of survey responses. Methodology Patients >40 years of age presenting at two Emergency Departments were eligible. Consenting patients were asked questions from a modified One-Minute Osteoporosis Risk Test. Modifiable, fixed, and total (modifiable risks + fixed risks) risk sums were calculated. For the association test, chi-square and Wilcoxon rank-sum tests were used. Four total risk categories were created (0-1, 2-3, 4-5, 6+). Odds of being in a higher risk category were analyzed using univariate ordinal logistic regression. Results The prevalence of both a fixed and modifiable risk was 62.2%. Women were more likely than men to report a risk (81.2% vs. 67.5%; p = 0.0043) and to be in a higher risk category (odds ratio (OR) [95% confidence interval (CI)] = 1.63 [1.09-2.45]; p = 0.018). Evidence strongly indicated an unadjusted association of race and modifiable risk category (p < 0.001), with more than half of African Americans (53.0%) in the highest category compared to 26.0% of whites. The total risk was higher in African Americans than whites (OR [95% CI] = 1.75 [1.15-2.67]; p = 0.010). Conclusions Race and gender were associated with specific risk factors. The Emergency Department proved to be a feasible location for conducting health maintenance screenings and should be considered for patient-specific routine osteoporosis risk screenings.

Impact of eyeglasses on academic performance in primary school children.

OBJECTIVE: To assess the impact of eyeglass administration after a vision-screening program on standardized testing scores in school-aged children. DESIGN: Retrospective study of children who participated in a vision-screening program that provided free eyeglasses where indicated. PARTICIPANTS: Students in kindergarten through grade 5 in a large urban school district in North America. METHODS: Children in kindergarten through grade 3 were administered the Developmental Reading Assessment (DRA), and children in grades 3 through 5 were administered the Pennsylvania System of School Assessment (PSSA). Classroom teachers completed eyeglass adherence questionnaires. RESULTS: A total of 4523 children participated in the vision-screening program. Eyeglasses were worn most of the time (>75%) by 67.4% of the children and never or rarely worn (<25%) by 18.6% of children. DRA results were available for 2226 children. When eyeglasses were prescribed and worn, initially high reading performances (DRA level 3) were less likely to decline (odds ratio [OR] = 4.36, p < 0.001). Improvement was not observed for children who initially scored DRA level 1 or 2 (OR = 0.29, p < 0.001 and OR = 1.00, p = 0.986, respectively). PSSA reading results were available for 847 children. When eyeglasses were prescribed and worn, Asian children were more likely to score higher PSSA reading levels (OR = 2.53, p = 0.004). This trend was also observed in black and Hispanic children without reaching statistical significance (OR = 1.70, p = 0.061; OR = 2.67, p = 0.067, respectively). CONCLUSIONS: In some children, wearing eyeglasses was associated with maintenance in standardized reading scores. High adherence to wearing eyeglasses suggests that children perceive a benefit, perhaps beyond that which these standardized test results were able to document.

Patient satisfaction and cosmetic outcome in a randomized study of cesarean skin closure.

Objective: To evaluate patient satisfaction and patient and physician assessment of scar appearance after cesarean skin closure with suture versus staples. Methods: Women undergoing cesarean delivery (CD) at ≥23 weeks' gestation via low-transverse skin incisions at three hospitals in the CROSS Consortium were randomized to receive skin closure using subcuticular absorbable suture or nonabsorbable metal staples. The primary outcome of this substudy, patient satisfaction, was assessed by surveys at the postpartum visit using a 10-point Likert scale. Scar outcomes according to patients and trained observers were assessed at the primary research site using the Patient and Observer Scar Assessment Scale (POSAS). The POSAS is comprised of a patient-completed assessment including subjective data such as pain and itchiness, and an observer-completed assessment about cosmetic criteria. Results: Between June 2010 and August 2012, 746 women were randomized; 370 received suture and 376 received staples. Satisfaction data were available for 606 (81%). Complete patient scar assessment data were available for 577 (77%) and complete observer scar assessment data were available for 275 (57% of the 480 planned for evaluation at the primary research site). Demographic data for women in the two groups were similar. Satisfaction with the closure method was higher (superior) among women who received suture closure: median 10 (interquartile range 9, 10) versus 9 (interquartile ranges (IQR) 6, 10); p < .01. The suture group also had higher satisfaction with the scar's appearance at the postpartum visit: median nine (IQR 7, 10) versus 8 (IQR 6, 10); p = .02. Receiving one's preferred closure method was associated with higher patient satisfaction, and wound complications were associated with lower satisfaction. POSAS scores were superior (lower) in the suture group. Patient Scar Assessment Scale scores were median 15 (IQR 10, 25) for sutures versus 20 (IQR 11, 28) for staples; p < .01. Observer Scar Assessment Scale scores were median 12 (IQR 9, 15) for sutures versus 13 (IQR 9, 16) for staples; p = .01. Conclusions: Satisfaction with the closure method, satisfaction with the scar's appearance, and patient and physician assessments of scar cosmesis were all superior in those closed with suture. These results further support the use of sutures for cesarean skin closure.

Esophageal adenocarcinoma in a first-degree relative increases risk for esophageal adenocarcinoma in patients with Barrett's esophagus.

Background: The significance of a family history of esophageal adenocarcinoma in the progression to esophageal adenocarcinoma in patients with Barrett's esophagus has not been thoroughly evaluated. The purpose of this study is to evaluate the presence of esophageal adenocarcinoma in a first-degree relative in patients with Barrett's esophagus. Methods: A retrospective cohort study was conducted of patients with Barrett's esophagus at a tertiary care center undergoing radiofrequency ablation. Family history, demographics, and pathology and endoscopy reports were assessed in all patients. Findings: Three hundred and one patients with Barrett's esophagus were assessed. Nineteen patients who had a diagnosis of esophageal adenocarcinoma on index endoscopy were excluded. Nineteen (6.7%) patients had a first-degree relative with esophageal adenocarcinoma. Four (21.1%) of these patients progressed to esophageal adenocarcinoma. Of patients without first-degree relative with esophageal adenocarcinoma 22/263 (8.7%) progressed to esophageal adenocarcinoma. In a logistic regression model adjusted for sex and the number of radiofrequency ablation treatments, we found that family history of esophageal adenocarcinoma was a significant independent predictor of progression to esophageal adenocarcinoma (odds ratio = 5.55, 95% confidence interval: 1.47-20.0). Conclusion: Our study indicates that Barrett's esophagus patients with a first-degree family member with esophageal adenocarcinoma are at 5.5-fold higher risk for disease progression to esophageal adenocarcinoma. Family history of esophageal adenocarcinoma in Barrett's esophagus patients should be considered in patient surveillance and radiofrequency ablation treatment, beyond recommended guidelines.

A Proposed Intervention to Decrease Resident-Performed Cataract Surgery Cancellation in a Tertiary Eye Care Center.

BACKGROUND: Cataracts are the leading cause of preventable blindness globally. As a result, competence in cataract surgery is an important component of ophthalmology residency training. Residency programs must optimize the number of cataract surgery cases to train proficient physicians. However, the rate of cataract surgery cancellations is high, and some are canceled because of preventable causes. OBJECTIVE: To evaluate the effect of mandatory on-site preadmission testing, including having a physical examination, on resident-performed cataract surgery cancellation rates. METHODS: For this study, patients scheduled for cataract surgery at the Wills Eye Hospital resident cataract clinic between January 2015 and November 2015 were enrolled and randomized into 2 groups: usual care or intervention. The patients randomized to the usual care group were instructed to complete preadmission testing and to have a physical examination with their primary care physician. The patients randomized to the intervention group were escorted to a Wills Eye Hospital-affiliated cardiologist to complete preadmission testing and to have a physical examination. Patients in both groups received a reminder call before the cataract surgery. RESULTS: A total of 441 patients were included in the study-240 patients in the usual care group and 201 patients in the intervention group. The overall cataract surgery cancellation rate was 14.5%; the rate was 12.4% in the intervention group and 16.3% in the usual care group (P = .28). The patients receiving the intervention were more likely to have preadmission testing and a physical examination than the patients in the usual care arm (P <.001). CONCLUSIONS: Facilitating the completion of preadmission testing for patients decreased the rates of resident-performed cataract surgery cancellation at a Wills Eye Hospital resident clinic and has the potential to improve patient outcomes and prevent blindness.

The Combination of Pancreas Texture and Postoperative Serum Amylase in Predicting Pancreatic Fistula Risk.

Postoperative pancreatic fistula (PF) remains one of the most significant complications after pancreaticoduodenectomy (PD). Recently, studies have suggested that post-PD serum hyperamylasemia (HA) may be a risk factor. In this study, we evaluate the relationship of pancreas texture and post-operative serum amylase levels in determining PF risk. This retrospective cohort study evaluated all patients who underwent PD at Thomas Jefferson University from 2009 to 2014. The highest postoperative serum amylase level from postoperative day (POD) 0 to POD 5 was obtained. Chi-square analyses and odds ratio (OR) evaluated the relationship between pancreas texture, serum amylase level, and the development of PF. Data from 524 consecutive patients were analyzed. Serum amylase threshold value of 165 IU/L yielded greatest accuracy from the receiver operating characteristic curve analysis (Sensitivity, 0.70; specificity, 0.72). Grade B or C PF were more common among HA patients (20 vs 3%; P < 0.001). HA was associated with increased rates of PD-associated complications. On multivariable analysis, early postoperative serum HA was more predictive of PF risk (OR, 4.87; P < 0.001) than either pancreatic duct size ≤3 mm (OR, 2.97; P = 0.01) or pancreas texture (OR,1.87; P = 0.05). CONCLUSION: The presence of HA on POD 0 or POD 1 is more predictive than soft pancreas texture or small pancreas duct size alone.

Patient Symptoms Are the Most Frequent Indicators of Recurrence in Patients with American Joint Committee on Cancer Stage II Melanoma.

BACKGROUND: Patients with stage II melanoma have a considerable risk for recurrence. Current guidelines are imprecise as to optimal follow-up. We hypothesized that by examining recurrence patterns, we could help to better inform guidelines. STUDY DESIGN: We queried IRB-approved melanoma databases of Thomas Jefferson University and University of North Carolina, identifying 581 patients with stage II melanoma between 1996 and 2015 with at least 1 year of follow-up. Data included location of first recurrence and how recurrence was detected (ie patient symptom, physician examination, or routine surveillance imaging). Cox regression with backward elimination was used for multivariable analysis. RESULTS: One hundred and seventy-one patients had a recurrence (29.4%), the incidence increased considerably by stage sub-group. Significant predictors of recurrence included male sex (p = 0.003), ulceration (p = 0.03), and stage (p < 0.001). On multivariable analysis, male sex and stage continued to be significant (p < 0.01). For overall survival, regression, ulceration, stage, and age were significant predictors of survival. Stage, regression, and age remained significant by multivariable analysis. Patient symptoms were the most frequent mode of detection (40%), followed by physician examination (30%) and surveillance imaging (26%)-this did not differ significantly by stage. Regional nodes were the most common site of recurrence (30%), followed by lung (27%) and in-transit (18%). CONCLUSIONS: The majority of recurrences in stage II melanoma are detected by patients and their physicians and rarely by routine imaging. As such, clinical follow-up and patient education are critical factors in detection of recurrence. With the prevalence of regional nodal recurrences, ultrasound might prove to be an important strategy in early recurrence detection.

Sleep-dependent plasticity requires cortical activity.

Recent findings in humans and animals suggest that sleep promotes synaptic plasticity, but the underlying mechanisms have not been identified. We have demonstrated recently an important role for sleep in ocular dominance (OD) plasticity, a classic form of in vivo cortical remodeling triggered by monocular deprivation (MD) during a critical period of development. The mechanisms responsible for the effects of sleep on OD plasticity are unknown but may depend on neuronal activity in the sleeping brain. We investigated the role of cortical activity in sleep-dependent plasticity by reversibly inactivating the sleeping visual cortex (V1) after a period of MD. Critical period cats were bilaterally implanted with cannulas in V1 and standard EEG/EMG electrodes for polysomnographic recording. After a period of MD, visual cortices were infused with the sodium channel blocker lidocaine in vehicle or vehicle only during sleep. A third group of cats served as sham controls and were infused with lidocaine outside of V1 (into the CSF). Both optical imaging of intrinsic cortical signals and microelectrode recordings showed that OD plasticity was significantly reduced in cats whose visual cortices were reversibly silenced during sleep. These findings demonstrate that the mechanisms governing this form of sleep-dependent plasticity require cortical activity. They provide an important insight into how sleep modifies synaptic circuitry by narrowing the range of possible candidate mechanisms to those that are activity dependent.

Improving access to vision screening in urban Philadelphia elementary schools.

BACKGROUND: The Wills Eye Vision Screening Program for Children is a community-based vision screening program for children in urban Philadelphia elementary schools that aims to provide vision screening, remedy refractive error by providing glasses, and refer children with suspected nonrefractive eye disease for eye care. METHODS: Children in grades K-5 from 45 Philadelphia elementary schools were screened for distance and near visual acuity, stereopsis, and color vision from January 2014 to June 2015. Children who failed were assessed by an on-site optometrist. Two pairs of eyeglasses were provided at no cost. Children with suspected, nonrefractive disease were referred to Wills Eye Hospital Pediatric Ophthalmology and contacted by a social worker to schedule an appointment. RESULTS: Over 84 days, 10,726 children were screened for vision problems at 45 schools. A total of 1,321 children (12%) had refractive error and 1,015 children (77%) returned the consent form and received two pairs of glasses. Of the 509 children (5%) referred to Wills Eye, 177 returned consent forms and were not being followed by an ophthalmologist. Of these, 127 children (72%) completed an eye examination at Wills. CONCLUSIONS: The program described herein can provide comprehensive vision screening, with eyeglasses and/or referrals, to children within an underserved community.

Dielectrophoresis of Caenorhabditis elegans.

We demonstrate for the first time the dielectrophoretic trapping and manipulation of a whole animal, the nematode Caenorhabditis elegans. We studied the effect of the electric field on the nematode as a function of field intensity and frequency. We identified a range of electric field intensities and frequencies that trap worms without apparent adverse effect on their viability. Worms tethered by dielectrophoresis (DEP) exhibit behavioral responses to blue light, indicating that at least some of the nervous system functions are unimpaired by the electrical field. DEP is useful to dynamically tether nematodes, sort nematodes according to size, and separate dead worms from live ones.