Publication rate and evidence-based evaluation of abstracts presented at the annual European College of Veterinary Surgeons scientific meeting.

OBJECTIVES: To determine the publication rate of abstracts presented at 10 European College of Veterinary Surgeons conferences from 2006 to 2015, report the key publication milestones, and determine variables associated with full manuscript publication. STUDY DESIGN: Literature review. SAMPLE POPULATION: One thousand thirty-eight abstracts. METHODS: All conference abstracts (n = 1038) from the 2006 to 2015 annual ECVS scientific meetings were reviewed, and final publication was determined through a comprehensive bibliographic search. Categories for the level of evidence (LoE), subject, discipline, and institution affiliation were assigned for each abstract. Dates of manuscript submission, acceptance, and publication were recorded. RESULTS: The overall publication rate for ECVS abstracts from 2006 to 2015 was 32%. Abstracts with levels 4 (60%) and 5 (23%) evidence were presented the most at ECVS conferences and had the highest publication rates at 38% and 36%, respectively. Key publication milestones showed that most abstracts (83%) received publication within the first 36 months with most LoE 2 abstracts (91%) being published within 24 months of presentation. Most published abstracts were affiliated with academic institutions (85%), on dog (29%) and horse (27%) subjects, focused on orthopedic (35%) and soft tissue disciplines (27%), and published in Veterinary Surgery (32%). CONCLUSION: The ECVS abstract publication rate was lower, and timeline was longer to publish than other veterinary surgical conferences. Publication occurred most frequently in academic institutions, in select journals, and was limited to orthopedic, soft-tissue, dog, and horse studies. CLINICAL SIGNIFICANCE: Results from this study may help improve the publication fate of abstracts in veterinary surgery. Additionally, caution is warranted when using information from abstracts that have yet to be published to help guide clinical decisions.

Evaluation of neurological behaviour in late-preterm newborn infants using the Hammersmith Neonatal Neurological Examination.

AIM: We hypothesise that clinically well late-preterm infants (LPI) (34+0 -36+6 weeks) are neurologically more immature than their term counterparts, and this immaturity persists even when these infants reach term-corrected age (TCA). The primary aim of our study was to characterise and contrast the neurodevelopmental profile of well LPI with full-term infants (FTI) (39+0 -41+6 weeks) using the Hammersmith Neonatal Neurological Examination (HNNE). Our secondary aim was to obtain local reference ranges for the 34 items in the HNNE in an Asian-dominant population. METHODS: LPI were assessed at two time points: 12-72 h of life and at TCA of 39+0 -41+6 weeks, while FTI were assessed at 12-72 h of life using the HNNE. Each of the 34 items on the HNNE was assigned an optimality score (OS) of 0, 0.5 or 1, totalling up to 34. A quantitative comparison of the neurobehavioral patterns was made using two-sample t-tests. RESULTS: A total of 212 infants (79 LPI and 133 FTI) were recruited. Mean OSs for LPI and FTI at birth were (25.11 ± 3.36)/34 and (31.19 ± 1.50)/34, respectively, with a mean difference of 6.08 (P value <0.0001). The mean OS for LPI on reaching TCA was (28.91 ± 2.30)/34, with a mean difference of 2.28 (P value <0.0001). Reference OSs for the 34 items on the HNNE were also obtained. CONCLUSION: LPI are more immature than their term counterparts even on reaching TCA, with discrepancies most apparent in 'tone' and 'movement'. We provide reference OSs of 34 items in the HNNE for infants in an Asian-dominant population.

Gastroesophageal reflux disease and paraneoplastic neurological syndrome associated with long-term survival in limited stage small-cell lung cancer.

INTRODUCTION: Patients with small-cell lung cancer (SCLC) have a very poor prognosis. However, a subset of SCLC achieves long-term survival. The objective of this study was to investigate factors and pattern of long-term survival in patients with limited-stage small cell lung cancer (LS-SCLC) who achieved a complete response (CR) after chemoradiotherapy. PATIENT AND METHODS: This was a single-center retrospective study. The analysis of hazard ratio (HR) and 95% confidence interval (CI) was performed using Cox proportional hazards model. For pattern analysis, the date of recurrence was used as the endpoint. The nominal categorical variables were analyzed by the χ2 test. Survival was estimated using the Kaplan-Meier model, and the results were reported as the median and interquartile range. RESULTS: We identified 162 patients, median age was 64.7 (56.2-70.2) years, and 94 (58%) were females. Eighty-one patients (50%) had recurrence during follow-up. Gastroesophageal reflux disease (GERD) (HR, 0.65; 95% CI, 0.45-0.93; p = 0.016) and neurological paraneoplastic syndrome (PNS) (HR, 0.46; 95% CI, 0.29-0.72; p < 0.001) were independent factors associated with improved overall survival (OS). Patients with GERD had prolonged recurrence free survival (RFS) compared to patients without GERD (median, 29.1 months vs. 13.9 months, p < 0.001), whereas patients with neurological PNS had a reduced recurrence rate compared to those patients without neurological PNS (No. [%], 8 [20.5] vs. 73 [59.3], p < 0.001). CONCLUSIONS: Patients with LS-SCLC achieving a CR after chemoradiotherapy, GERD, and neurological PNS were associated with improved OS. GERD and neurological PNS were associated with longer RFS and lower recurrence rate, respectively.

Characteristics of Veterans With Non-VA Encounters Enrolled in a Trial of Standards-Based, Interoperable Event Notification and Care Coordination.

INTRODUCTION: Understanding how veterans use Veterans Affairs (VA) for primary care and non-VA for acute care can help policy makers predict future health care resource use. We aimed to describe characteristics of veterans enrolled in a multisite clinical trial of non-VA acute event notifications and care coordination and to identify patient factors associated with non-VA acute care. METHODS: Characteristics of 565 veterans enrolled in a prospective cluster randomized trial at the Bronx and Indianapolis VA Medical Centers were obtained by interview and chart review. RESULTS: Veterans' mean age was 75.8 years old, 98.3% were male, and 39.2% self-identified as a minority race; 81.2% reported receiving the majority of care at the VA. There were 197 (34.9%) veterans for whom a non-VA acute care alert was received. Patient characteristics significantly associated with greater odds of a non-VA alert included older age (OR = 1.05; 95% CI, 1.04-1.05); majority of care received is non-VA (OR = 1.83; 95% CI, 1.06-3.15); private insurance (OR = 1.39; 95% CI, 1.19-1.62); and higher income (OR = 4.01; 95% CI, 2.68-5.98). CONCLUSIONS: We identified several patient-level factors associated with non-VA acute care that can inform the design of VA services and policies for veterans with non-VA acute care encounters and reintegration back into the VA system.

Small-cell Lung Cancer in Very Elderly (≥ 80 Years) Patients.

BACKGROUND: This analysis was performed to describe the outcome of very elderly (≥ 80 years) patients with small-cell lung cancer (SCLC) as there is no published data regarding these patients. MATERIALS AND METHODS: One hundred forty-six very elderly patients with SCLC were identified from the Institutional Lung Cancer Database ranging in age from 80 to 92 years (median, 82 years). Of these, 47 (32%) patients had limited-stage SCLC (L-SCLC), and 99 (68%) had extensive-stage SCLC (E-SCLC). All were Caucasian, and the majority (64%) were female. Sixty-seven (46%) patients had Zubrod performance status (PS) of 0 to 1. RESULTS: Of the 146 patients, 44 (30%) received no therapy, 65 (45%) received chemotherapy alone, 27 (19%) received chemotherapy plus local therapy (thoracic radiotherapy [TRT] or surgery), and 10 (7%) received local therapy alone. The median survival was 5.4 months. On univariable analysis, age (P = .019), stage (L-SCLC vs. E-SCLC; P = .0002), PS (P < .0001), and treatment option (P < .0001) were associated with survival. On multivariable analysis, stage (P = .011), PS (P = .029), and treatment option (P < .0001) maintained significance. For entire cohort, the median survival was 1.3 months without active therapy, 6 months with local therapy alone, 7.2 months with chemotherapy alone, and 14.4 months with chemotherapy plus local therapy (P < .0001, univariable and multivariable). Similar survival findings in response to treatment were found when the L-SCLC and E-SCLC cohorts were separately analyzed. CONCLUSIONS: The survival of very elderly patients with SCLC was associated with stage (L-SCLC vs. E-SCLC), PS, and treatment option. Very elderly patients with SCLC often have limited functional reserve required to tolerate aggressive multimodality therapy but appeared to benefit from it. Geriatric assessments, careful monitoring, and extra support are warranted in elderly patients. Care should be individualized based on the desires and needs of each patient.

EGFR mediates activation of RET in lung adenocarcinoma with neuroendocrine differentiation characterized by ASCL1 expression.

Achaete-scute homolog 1 (ASCL1) is a neuroendocrine transcription factor specifically expressed in 10-20% of lung adenocarcinomas (AD) with neuroendocrine (NE) differentiation (NED). ASCL1 functions as an upstream regulator of the RET oncogene in AD with high ASCL1 expression (A+AD). RET is a receptor tyrosine kinase with two main human isoforms; RET9 (short) and RET51 (long). We found that elevated expression of RET51 associated mRNA was highly predictive of poor survival in stage-1 A+AD (p=0.0057). Functional studies highlighted the role of RET in promoting invasive properties of A+AD cells. Further, A+AD cells demonstrated close to 10 fold more sensitivity to epidermal growth factor receptor (EGFR) inhibitors, including gefitinib, than AD cells with low ASCL1 expression. Treatment with EGF robustly induced phosphorylation of RET at Tyr-905 in A+AD cells with wild type EGFR. This phosphorylation was blocked by gefitinib and by siRNA-EGFR. Immunoprecipitation experiments found EGFR in a complex with RET in the presence of EGF and suggested that RET51 was the predominant RET isoform in the complex. In the microarray datasets of stage-1 and all stages of A+AD, high levels of EGFR and RET RNA were significantly associated with poor overall survival (p < 0.01 in both analyses). These results implicate EGFR as a key regulator of RET activation in A+AD and suggest that EGFR inhibitors may be therapeutic in patients with A+AD tumors even in the absence of an EGFR or RET mutation.

A Randomized Phase IIb Trial of myo-Inositol in Smokers with Bronchial Dysplasia.

Previous preclinical studies and a phase I clinical trial suggested that myo-inositol may be a safe and effective lung cancer chemopreventive agent. We conducted a randomized, double blind, placebo-controlled phase IIb study to determine the chemopreventive effects of myo-inositol in smokers with bronchial dysplasia. Smokers with ≥1 site of dysplasia identified by autofluorescence bronchoscopy-directed biopsy were randomly assigned to receive oral placebo or myo-inositol, 9 g once a day for 2 weeks, and then twice a day for 6 months. The primary endpoint was change in dysplasia rate after 6 months of intervention on a per-participant basis. Other trial endpoints reported herein include Ki-67 labeling index, blood and bronchoalveolar lavage fluid (BAL) levels of proinflammatory, oxidant/antioxidant biomarkers, and an airway epithelial gene expression signature for PI3K activity. Seventy-four (n = 38 myo-inositol and n = 36 placebo) participants with a baseline and 6-month bronchoscopy were included in all efficacy analyses. The complete response and the progressive disease rates were 26.3% versus 13.9% and 47.4% versus 33.3%, respectively, in the myo-inositol and placebo arms (P = 0.76). Compared with placebo, myo-inositol intervention significantly reduced IL6 levels in BAL over 6 months (P = 0.03). Among those with a complete response in the myo-inositol arm, there was a significant decrease in a gene expression signature reflective of PI3K activation within the cytologically normal bronchial airway epithelium (P = 0.002). The heterogeneous response to myo-inositol suggests a targeted therapy approach based on molecular alterations is needed in future clinical trials to determine the efficacy of myo-inositol as a chemopreventive agent. Cancer Prev Res; 9(12); 906-14. ©2016 AACR.

Examining the Effectiveness of Action Plans Derived from the Root Cause Analysis of Incidents Occurring in a Radiation Therapy Department.

PURPOSE: In 2011, the Canadian Partnership for Quality Radiotherapy developed guidelines for quality improvement. In the same year, a large academic cancer centre initiated a program of root cause analysis (RCA) and incident learning for major incidents. RCAs were performed on seven incidents; more than 40 action items were developed with the intent to prevent these incidents from recurring. The aim of this study was to determine the efficacy of implementation of the six action items, evaluate radiation therapists' (RTTs') awareness of these new action items, and determine whether communication among staff members was satisfactory. METHODS AND MATERIALS: The study consisted of two components. Part one examined four action items using a questionnaire distributed to all RTTs at the cancer centre. Part two examined two action items by auditing the radiation treatment software, MOSAIQ. RESULTS: Staff communication and RTTs' awareness of the action items ranged from 71% to 98%. For the first four action items, although most RTTs were aware of them, only 40%-70% of RTTs always or often used these action items and considered them effective. The fifth action item, implementation of the new breast tolerance setting, had 51% more overrides after implementation. Further investigation indicated only 40% of the tangent breast setups had new tolerance settings applied. CONCLUSIONS: Communication plays an important role in the dissemination and application of interventions identified from an RCA. A standardized route of communication is required to ensure that all RTTs fully understand an action item. A follow-up program and continuous monitoring of the action items are key to an effective RCA program.

SH3GL2 is frequently deleted in non-small cell lung cancer and downregulates tumor growth by modulating EGFR signaling.

The purpose of this study was to identify key genetic pathways involved in non-small cell lung cancer (NSCLC) and understand their role in tumor progression. We performed a genome wide scanning using paired tumors and corresponding 16 mucosal biopsies from four follow-up lung cancer patients on Affymetrix 250K-NSpI array platform. We found that a single gene SH3GL2 located on human chromosome 9p22 was most frequently deleted in all the tumors and corresponding mucosal biopsies. We further validated the alteration pattern of SH3GL2 in a substantial number of primary NSCLC tumors at DNA and protein level. We also overexpressed wild-type SH3GL2 in three NSCLC cell lines to understand its role in NSCLC progression. Validation in 116 primary NSCLC tumors confirmed frequent loss of heterozygosity of SH3GL2 in overall 51 % (49/97) of the informative cases. We found significantly low (p = 0.0015) SH3GL2 protein expression in 71 % (43/60) primary tumors. Forced overexpression of wild-type (wt) SH3GL2 in three NSCLC cell lines resulted in a marked reduction of active epidermal growth factor receptor (EGFR) expression and an increase in EGFR internalization and degradation. Significantly decreased in vitro (p = 0.0015-0.030) and in vivo (p = 0.016) cellular growth, invasion (p = 0.029-0.049), and colony formation (p = 0.023-0.039) were also evident in the wt-SH3GL2-transfected cells accompanied by markedly low expression of activated AKT(Ser(473)), STAT3 (Tyr(705)), and PI3K. Downregulation of SH3GL2 interactor USP9X and activated ß-catenin was also evident in the SH3GL2-transfected cells. Our results indicate that SH3GL2 is frequently deleted in NSCLC and regulates cellular growth and invasion by modulating EGFR function.

Randomized phase II trial of sulindac for lung cancer chemoprevention.

INTRODUCTION: Sulindac represents a promising candidate agent for lung cancer chemoprevention, but clinical trial data have not been previously reported. We conducted a randomized, phase II chemoprevention trial involving current or former cigarette smokers (≥30 pack-years) utilizing the multi-center, inter-disciplinary infrastructure of the Cancer Prevention Network (CPN). METHODS: At least 1 bronchial dysplastic lesion identified by fluorescence bronchoscopy was required for randomization. Intervention assignments were sulindac 150mg bid or an identical placebo bid for 6 months. Trial endpoints included changes in histologic grade of dysplasia (per-participant as primary endpoint and per lesion as secondary endpoint), number of dysplastic lesions (per-participant), and Ki67 labeling index. RESULTS: Slower than anticipated recruitment led to trial closure after randomizing participants (n=31 and n=30 in the sulindac and placebo arms, respectively). Pre- and post-intervention fluorescence bronchoscopy data were available for 53/61 (87%) randomized, eligible participants. The median (range) of dysplastic lesions at baseline was 2 (1-12) in the sulindac arm and 2 (1-7) in the placebo arm. Change in dysplasia was categorized as regression:stable:progression for 15:3:8 (58%:12%:31%) subjects in the sulindac arm and 15:2:10 (56%:7%:37%) subjects in the placebo arm; these distributions were not statistically different (p=0.85). Median Ki67 expression (% cells stained positive) was significantly reduced in both the placebo (30 versus 5; p=0.0005) and sulindac (30 versus 10; p=0.0003) arms, but the difference between arms was not statistically significant (p=0.92). CONCLUSIONS: Data from this multi-center, phase II squamous cell lung cancer chemoprevention trial do not demonstrate sufficient benefits from sulindac 150mg bid for 6 months to warrant additional phase III testing. Investigation of pathway-focused agents is necessary for lung cancer chemoprevention.