tbuckley/cabot-search huggingface dataset:
The Influence of Body Mass Index on Overall Survival Following Surgical Resection of Non–Small Cell Lung Cancer
Authors: Boris Sepesi, Kathryn A. Gold, Arlene M. Correa, John V. Heymach, Ara A. Vaporciyan, Jason Roszik, Ethan Dmitrovsky, Xi Liu
Journal: Journal of Thoracic Oncology (2017)

BackgroundPopulation studies suggest that high body mass index (BMI) correlates with a reduced risk for death from lung cancer. The aim of our study was to evaluate definitively the influence of BMI on long-term overall survival (OS) in surgical patients with NSCLC.MethodsThe study population consisted of 1935 patients who underwent surgical resection for lung cancer at M. D. Anderson Cancer Center (2000–2014). Study variables included both patient- and treatment-related characteristics. Univariate and multivariate Cox regression analyses were performed to identify variables associated with OS.ResultsOn univariate analysis, significant predictors of improved survival were higher BMI, pathologic tumor stage (stage I versus stage II, III, or IV), type of surgical procedure (lobectomy/pneumonectomy versus wedge resection/segmentectomy), younger age, female sex, and adenocarcinoma histologic subtype (versus squamous) (all p < 0.05). Morbidly obese patients (BMI ≥ 35) demonstrated a trend toward better outcomes than those classified as obese (BMI ≥30 and <35 kg/m2) (p = 0.05), overweight (BMI ≥ 25 and <30 kg/m2) (p = 0.13), or healthy weight (BMI <25 kg/m2) (p = 0.37) (hazard ratio = 0.727, 0.848, 0.926, and 1, respectively). On multivariate analysis, BMI remained an independent predictor of survival (p = 0.02). Propensity matching analysis demonstrated significantly better OS (p = 0.003) in patients with a BMI of 30 kg/m2 or higher as compared with a BMI of 25 kg/m2.ConclusionsIn this large, retrospective, single-center series, after control for disease stage and other variables, higher BMI was associated with improved OS after surgical resection of NSCLC. Further studies are necessary to elucidate the precise relationship between BMI and treatment outcomes.
LGG-11. LOW-GRADE ASTROCYTOMA CORE MUTATIONS IN IDH1, P53 AND ATRX COOPERATE TO BLOCK DIFFERENTIATION OF HUMAN NEURAL STEM CELLS VIA EPIGENETIC REPRESSION OF SOX2
Authors: Aram Modrek, Danielle Golub, Themasap Khan, Jod Prado, Christopher Bowman, Jingjing Deng, Guoan Zhang, Pedro Rocha, Ramya Raviram, Harris Lazaris, Michael Kader, Joravar Dhaliwal, Andrew Chi, John Golfinos, Aristotelis Tsirigos, David Zagzag, Matija Snuderl, Jane Skok, Thomas Neubert, Dimitris Placantonakis
Journal: Neuro-Oncology (2017)

To model low-grade astrocytoma (LGA) formation, we introduced R132H IDH1, P53 shRNA and ATRX shRNA in human neural stem cells (NSCs). These oncogenic hits blocked NSC differentiation, increased invasiveness in vivo and led to an epigenetic and transcriptional profile resembling IDH1-mutant human LGAs. The differentiation block was caused by transcriptional silencing of transcription factor SOX2. Ectopic expression of SOX2 was sufficient to rescue the differentiation block. We found that SOX2 down-regulation was secondary to disassociation of its promoter from a putative long-range enhancer ~700kb downstream of SOX2. This occurred due to reduced binding of the chromatin organizer CTCF to its methylated DNA motifs and disrupted chromatin looping. Our human model of IDH-mutant LGA implicates impaired NSC differentiation due to epigenetic repression of SOX2 as an early driver of gliomagenesis.
IMMU-14. REMODELING IMMUNITY AGAINST MEDULLOBLASTOMA VIA RNA LOADED NANOPARTICLES
Authors: Elias Sayour, Gabriel De Leon, Adam Grippin, Catherine Flores, Christina Pham, Duane Mitchell
Journal: Neuro-Oncology (2017)

BACKGROUND: While recurrent medulloblastoma (MB) remains almost uniformly fatal, our group has shown a trend (p=0.07) toward improved progression-free survival in patients receiving autologous tumor RNA pulsed dendritic cells (DCs) coupled with ex vivo expanded total RNA activated T-cells. However, the advancement of autologous cellular therapeutics through the commercialization pipeline has been encumbered by significant cost, complexity and time to generation. To circumvent these challenges, we developed a novel treatment platform, which leverages the use of commercially available and clinically translatable nanoparticles (NPs) that can be combined with tumor-derived RNA to systemically activate peripheral immunity against MB antigens. OBJECTIVE: To overcome the limitations of poorly immunogenic local vaccination strategies, we assessed if intravenous delivery of tumor-derived RNA encapsulated in lipophilic NPs could systemically activate antigen presenting cells (APCs) for induction of therapeutic anti-tumor immunity in pre-clinical MB models. RESULTS: We identified a clinically translatable NP formulation for the delivery of RNA to APCs that induces in vivo gene expression and preserves RNA stability over time. When administered intravenously, RNA-NPs lead to systemic activation (i.e. MHCI/II, CD40, CCR7 and CD86) of host APCs within reticuloendothelial organs and within the intratumoral microenvironment. We demonstrated that both model-antigen encoding RNA and physiologically-relevant tumor-derived RNA, when encapsulated in NPs, could expand potent anti-tumor T-cell immunity. T-cell immunity elicited by RNA-NPs was superior to peptide vaccines formulated in complete Freund’s adjuvant. We enhanced the immunogenicity of this platform by simply combining mRNAs encoding for immunomodulatory molecules (i.e. HCV-PAMPs, GM-CSF). In a pre-clinical cellular immunotherapy model targeting an anaplastic murine MB, RNA NPs supersede DCs in mediating anti-tumor activity. CONCLUSION: Since RNA-NPs bypass cost/complexity of cellular therapeutics, are amenable to central distribution, and can be made within days of tumor-resection, these formulations supplant DCs by providing near-immediate immune induction for patients with recurrent MBs.
Allergic adverse events following 2015 seasonal influenza vaccine, Victoria, Australia
Authors: Hazel J Clothier, Nigel Crawford, Melissa A Russell, Jim P Buttery
Journal: Eurosurveillance (2017)

Australia was alerted to a possible increase in allergy-related adverse events following immunisation (AEFI) with 2015 seasonal trivalent influenza vaccines (TIV) by the Victorian state vaccine safety service, SAEFVIC. We describe SAEFVIC's initial investigation and upon conclusion of the 2015 influenza vaccination programme, to define the signal event and implications for vaccine programmes. Allergy-related AEFI were defined as anaphylaxis, angioedema, urticaria or generalised allergic reaction. Investigations compared 2015 TIV AEFI reports to previous years as proportions and reporting risk (RR) per 100,000, stratified by influenza vaccine brand. The initial investigation showed an increased proportion of allergy-related AEFI compared with 2014 (25% vs 12%), predominantly in adults, with insufficient clinical severity to alter the programme risk-benefit. While overall TIV AEFI RR in 2015 was similar to previous years (RR: 1.07, 95% confidence interval (CI): 0.88-1.29), we identified a near-doubling RR for allergy-related AEFI in 2015 (RR: 1.78, 95% CI: 1.14-- 2.80) from 2011 to 2014 with no difference by vaccine brand or severity increase identified. This increase in generalised allergy-related AEFI, across all used vaccine brands, supports evidence of variable reactogenicity arising from influenza vaccine strain variations. This investigation underlines the importance of effective seasonal influenza vaccine pharmacovigilance.
Defining parameters that can guide public cord blood units (CBUs) in Korea.
Authors: Junglim Lee, Jun Ho Ji
Journal: Journal of Clinical Oncology (2013)

7123 Background: It is well recognized that TNC and CD34 define a superior Cord blood unit (CBU). According to “the Law of Korean CB Banking and Research”, only 40% of collected CBUs meet the criteria. To improve a rate of banking, we analyzed the characteristics of CBUs and assessed predictive factors for numbers of TNC and CD34+ in collected CBUs. Methods: 2004 to 2012, CBUs donated to the Daegu Fatima Hospital Public CB Bank (n = 1074) were analyzed. The associations between TNC, CD34+ and variables including body weight (BW), GA, delivery type, gender, collecting volumes (CV) were analyzed by logistic regression analysis. Results: In our study cohort (n = 1074, male;553, female;521, all Koreans), the median value of TNC, numbers of CD34+, GA, BW and CV were 10.6úI10 8 /unit (6.0-35.1), 3.41úI10 6 /unit ( 0.8-27.0), 39 weeks (36-42 weeks), 3310g (1660-4600g) and 75.4ml (35-179ml) respectively. In univariate analysis, maternal /donor (M/D) characteristics that were associated with high TNC (&gt; 10úI10 8 ) included higher GA(GA &gt; 39 weeks) [OR 2.02 (95% CI 1.54-2.66 p &lt; 0.001)], normal delivery [OR 3.05 (95% CI 2.21-4.22 p &lt; 0.001)], female [OR 1.46 (95% CI 1.15-1.86 p=0.001)], BW &gt; 3310g [OR 2.05 (95% CI 1.60-2.60 p &lt; 0.001)] and CV&gt; 75ml [OR 6.99 (95% CI 5.34-9.14 p &lt; 0.001)].In multivariate analysis of TNC, CV &gt; 75ml [OR 7.91 (95% CI 5.92-10.56 p &lt; 0.001)] was the best predictor of followed by female [OR 1.73 (95% CI 1.30-2.30 p &lt; 0.001)], BW &gt; 3310g [OR 1.70 (95% CI 1.27-2.26 p &lt; 0.001)] and GA &gt; 39 weeks [OR 1.45 (95% CI 1.04-2.04 p = 0.03)]. In univariate analysis, M/D characteristics that were associated with high numbers of CD34+ (&gt;3x10 6 ) included normal delivery [OR 2.09 (95% CI 1.49-2.93 p &lt; 0.001)], BW &gt; 3310g [OR 1.94 (95% CI 1.52-2.47 p &lt; 0.001)] and CV &gt; 75ml [OR 3.22 (95% CI 2.51-4.14 p &lt; 0.001)]. In multivariate analysis of CD34+, CV &gt; 75ml [OR 3.13 (95% CI 2.43-4.05 p &lt; 0.001)] and BW &gt; 3310 [OR 1.84 (95% CI 1.41-2.40 p &lt; 0.001)] were significant predictors. Conclusions: M/D characteristics were associated with CV which is the best predictor followed by BW for both TNC and CD34+ in collected Korean CBUs. These associations could be used to prioritize donations, collections, optimizing and financial modeling in Korean CB banks.
Interim analysis of a phase 1, open-label, dose-escalation study of SGN-CD19A in patients with relapsed or refractory B-lineage non-Hodgkin lymphoma (NHL).
Authors: Andres Forero-Torres, Craig Moskowitz, Ranjana H. Advani, Bijal D. Shah, Ana Kostic, Tina M. Albertson, Larissa Sandalic, Baiteng Zhao, Michelle A. Fanale
Journal: Journal of Clinical Oncology (2014)

8505 Background: CD19, a member of the immunoglobulin superfamily, is expressed in most patients with B-cell NHL. SGN-CD19A is a novel antibody-drug conjugate composed of a humanized anti-CD19 monoclonal antibody conjugated to the microtubule-disrupting agent monomethyl auristatin F (MMAF) via a maleimidocaproyl linker. Methods: This phase 1, open-label, dose-escalation study investigates the safety, tolerability, pharmacokinetics (PK), and antitumor activity of SGN-CD19A in patients with relapsed or refractory B-cell NHL with at least 1 prior systemic regimen (NCT01786135). Patients with DLBCL or follicular lymphoma grade 3 (FL3) must have received intensive salvage therapy. A modified continual reassessment method is used for dose allocation and maximum tolerated dose (MTD) estimation. SGN-CD19A is given by IV on Day 1 of 21-day cycles. Results: To date, 22 patients with a median age of 63 years (range, 33 to 81) with DLBCL (18), MCL (3), and FL3 (1) have been treated with SGN-CD19A. 50% of patients were refractory to their last treatment; 6 patients received prior autologous SCT. Patients have received a median of 2 cycles (range, 1 to 9) at dose levels from 0.5 mg/kg to 6 mg/kg. 11 patients remain on treatment and 11 have discontinued due to progressive disease (10) and patient decision (1). No dose-limiting toxicity (DLT) has been reported in 21 DLT-evaluable patients; the MTD has not yet been identified. Adverse events occurring in ≥10% of patients are fatigue (27%), blurred vision (27%), dry eye (23%), constipation (23%), dyspnea (14%), and keratitis (14%). Of the 20 patients evaluated, objective responses were observed in 8 patients (40%), 6 CRs (30%) and 2 PRs (10%); 3 patients had SD (15%) and 9 had PD (45%). SGN-CD19A ADC plasma exposures were approximately dose-proportional in preliminary PK analysis with mean terminal half-lives between 9-30 days. Conclusions: To date, SGN-CD19A has shown evidence of clinical activity with an objective response rate of 40% (8 of 20 patients) and an observed CR rate of 30% (6 of 20 patients). No DLTs have been reported in tested dose levels; enrollment is ongoing to identify the optimal dose of SGN-CD19A for future studies. Clinical trial information: NCT01786135.
LGG-10. PROTEOGENOMICS DISCRIMINATES PEDIATRIC AND ADULT PILOCYTIC ASTROCYTOMA AS DISTINCT BIOLOGICAL ENTITIES
Authors: Daniel Picard, Jörg Felsberg, Maike Langini, David Pauck, Viktoria Marquardt, Frauke Meyer, Anja Stefanski, Kai Stühler, Arndt Borkhardt, Guido Reifenberger, Cláudia Faria, Marc Remke
Journal: Neuro-Oncology (2017)

Pilocytic astrocytoma (PA) is a well-circumscribed, slow growing, low-grade brain tumor predominantly affecting children and considered a single-pathway disease with activation of MAPK signaling, typically driven by BRAF alterations. While five-year overall survival rates exceed 95%, incompletely resected tumors recur frequently despite radiation and/or chemotherapy. Less favorable responses to multimodal therapies are observed in adults compared to pediatric patients. Thus, we utilized a proteogenomics approach to discern the biological heterogeneity of PA across all age-groups to identify novel therapeutic targets. Our proteogenomic approach encompasses RNA sequencing (RNAseq) and LC/MS-based proteomic profiling in a cohort of pediatric (n=55) and adult cases (n=24). Unsupervised hierarchical clustering is used to determine the biological heterogeneity of the disease. Integrative genomics, combined with downstream pathway analysis, dissects aberrant pathway activation in biological subgroups. Lastly, we utilize a drug screening pipeline encompassing conventional chemotherapeutics and targeted therapeutics (n=211) currently evaluated in phase III and IV clinical trials to validate novel molecular targets in PA culture models (n=8). Pediatric and adult PA segregate into two subgroups identified by unsupervised hierarchical clustering using RNAseq and proteomic profiling (p=0.001). Adult tumors form a single entity, while we observed additional heterogeneity in pediatric tumors segregating into two subgroups (p=0.01). Initial analyses show that adult PA demonstrate an over-representation of genes involved in translation initiation and ciliogenesis according to GeneSet Enrichment Analysis, whereas pediatric PA show a significant enrichment of pathways involved in glycolysis, signal transmission and AKT signaling. In all, our proteogenomic approach reveals important biological heterogeneity in pediatric and adult PA. Ongoing drug profiling is used to determine therapeutics with preferential activity against pediatric and adult PA cultures compared to neural stem cells and astrocytes. These biological insights may improve biological classification and reveal novel therapeutic targets specifically useful for non-resectable tumors with high risk of progressive disease.
Predictors of recommended academic adjustments among concussed student-athletes presenting to the primary care setting
Authors: Erin Wasserman, Mackenzie Herzog, Johna Register-Mihalik, Valerie De Maio, Janna Fonseca, Kristen Phillips, O. Josh Bloom
Journal: British Journal of Sports Medicine (2017)

Objective The purpose was to describe academic ajdustments recommended by primary care physicians to paediatric concussion patients and to identify predictors of recommended adjustments. Design Prospective cohort. Setting Primary care sports medicine clinic. Subjects Participants were 8–18 years old, injured during organised or recreational sports, and presented to the clinic within 3 days of concussion. Intervention Symptom scores, average visual near-point convergence, and ImPACT composite scores were evaluated as predictors of accommodations using logistic regression. Outcome measures Academic adjustment information was obtained from a standardised, provider completed form. Patients with no recommendation form were excluded (N=31). Academic accommodations were grouped into: 1) cognitive (e.g. limited or no testing, extra time for schoolwork) and 2) visual-vestibular (e.g. auditory participation only, limited visual stimulants). Results 163 patients met the inclusion criteria; 88 (54%) were male. The mean age was 14.3±2.2 years. Most patients received academic adjustment recommendations (N=140; 86%). 21 (13%) received cognitive recommendations, 13 (8%) visual-vestibular, and 105 (64%) both. The most common recommendations were: “Take rest breaks during the day as needed” (N=108, 66%), “Patient is to limit visual stimulants and screen time” (N=102, 63%), and “Allow extra time to complete tasks” (N=97, 60%). Patients with higher symptom scores (OR=1.03 per 1-point increase; 95% CI: 1.00–1.05; p=0.03) and lower processing speed scores (OR=1.07 per 1-point decrease; 95% CI: 1.01–1.13; p=0.02) were more likely to receive visual-vestibular accommodations. There were no significant predictors of cognitive adjustments. Conclusions Most student-athletes received academic adjustment recommendations. Symptom and neurocognitive measures may aid clinicians in decision-making about academic adjustments. Competing interests Study funded in part by a research grant from the National Operating Committee on Standards for Athletic Equipment. Ms. Fonseca is employed at the study setting. Ms. Phillips is employed at the study setting. Dr. Bloom is employed at the study setting.
GP is suspended for 12 months for treatment failures in four patients
Authors: Clare Dyer
Journal: BMJ (2017)

An experienced GP who wrongly diagnosed addiction to painkillers in a patient and then failed to suspect an ectopic pregnancy when she returned with abdominal pain has been suspended for 12 months by a medical practitioners tribunal in Manchester.

Shahabuddin Syed, who qualified in India but has worked in the UK since 1971, largely in Kent, was found guilty of serious misconduct in his treatment of all four patients considered in the case. He was also found to have been rude to a social worker who had called him out to see one of the patients.

The social worker had asked Syed to make a home visit to an elderly woman, referred to as Patient A, who had recently been admitted to …
What domains of clinical function should be assessed after sport-related concussion? A systematic review
Authors: Nina Feddermann-Demont, Ruben J Echemendia, Kathryn J Schneider, Gary S Solomon, K Alix Hayden, Michael Turner, Jiří Dvořák, Dominik Straumann, Alexander A Tarnutzer
Journal: British Journal of Sports Medicine (2017)

<h3>Background</h3> Sport-related concussion (SRC) is a clinical diagnosis made after a sport-related head trauma. Inconsistency exists regarding appropriate methods for assessing SRC, which focus largely on symptom-scores, neurocognitive functioning and postural stability. <h3>Design</h3> Systematic literature review. <h3>Data sources</h3> MEDLINE, EMBASE, PsycINFO, Cochrane-DSR, Cochrane CRCT, CINAHL, SPORTDiscus (accessed July 9, 2016). <h3>Eligibility criteria for selecting studies</h3> Original (prospective) studies reporting on postinjury assessment in a clinical setting and evaluation of diagnostic tools within 2 weeks after an SRC. <h3>Results</h3> Forty-six studies covering 3284 athletes were included out of 2170 articles. Only the prospective studies were considered for final analysis (n=33; 2416 athletes). Concussion diagnosis was typically made on the sideline by an (certified) athletic trainer (55.0%), mainly on the basis of results from a symptom-based questionnaire. Clinical domains affected included cognitive, vestibular and headache/migraine. Headache, fatigue, difficulty concentrating and dizziness were the symptoms most frequently reported. Neurocognitive testing was used in 30/33 studies (90.9%), whereas balance was assessed in 9/33 studies (27.3%). <h3>Summary/conclusions</h3> The overall quality of the studies was considered low. The absence of an objective, gold standard criterion makes the accurate diagnosis of SRC challenging. Current approaches tend to emphasise cognition, symptom assessment and postural stability with less of a focus on other domains of functioning. We propose that the clinical assessment of SRC should be symptom based and interdisciplinary. Whenever possible, the SRC assessment should incorporate neurological, vestibular, ocular motor, visual, neurocognitive, psychological and cervical aspects.
Factors Associated With Diabetes-Specific Health-Related Quality of Life in Youth With Type 1 Diabetes: The Global TEENs Study
Authors: Barbara J. Anderson, Lori M. Laffel, Catherine Domenger, Thomas Danne, Moshe Phillip, Carmen Mazza, Ragnar Hanas, Sheridan Waldron, Roy W. Beck, Francoise Calvi-Gries, Chantal Mathieu
Journal: Diabetes Care (2017)

OBJECTIVE Our objective was to characterize diabetes-specific health-related quality of life (D-HRQOL) in a global sample of youth and young adults with type 1 diabetes (T1D) and to identify the main factors associated with quality of life. RESEARCH DESIGN AND METHODS The TEENs study was an international, cross-sectional study of youth, 8–25 years of age, with T1D. Participants (N = 5,887) were seen in clinical sites in 20 countries across 5 continents enrolled for 3 predetermined age groups: 8–12, 13–18, and 19–25 years of age. To assess D-HRQOL, participants completed the PedsQL Diabetes Module 3.0 and were interviewed about family-related factors. Specifics about treatment regimen and self-management behaviors were collected from medical records. RESULTS Across all age groups, females reported significantly lower D-HRQOL than did males. The 19–25-year age group reported the lowest D-HRQOL. Multivariate linear regression analyses revealed that D-HRQOL was significantly related to HbA1c; the lower the HbA1c, the better the D-HRQOL. Three diabetes-management behaviors were significantly related to better D-HRQOL: advanced methods used to measure food intake; more frequent daily blood glucose monitoring; and more days per week that youth had ≥30 min of physical activity. CONCLUSIONS In all three age groups, the lower the HbA1c, the better the D-HRQOL, underscoring the strong association between better D-HRQOL and optimal glycemic control in a global sample of youth and young adults. Three diabetes-management behaviors were also related to optimal glycemic control, which represent potentially modifiable factors for clinical interventions to improve D-HRQOL as well as glycemic control.
Роль біомаркерів у діагностиці хронічних запальних захворювань кишечника
Authors: Yu.M. Stepanov, I.V. Psareva
Journal: GASTROENTEROLOGY (2017)

Хронічні запальні захворювання кишечника, а саме неспецифічний виразковий коліт та хвороба Крона, привертають увагу як лікарів, так і науковців у всьому світі. Відзначена тенденція до зростання числа тяжких, резистентних до лікування форм захворювань, ускладнень та оперативних втручань, що призводять до інвалідизації пацієнтів молодого, працездатного віку. Проблема діагностики запальних захворювань кишечника дотепер залишається однією з найбільш тяжко вирішуваних у гастроентерологічній практиці. У статті відображені питання діагностики хронічних запальних захворювань кишечника (неспецифічний виразковий коліт, хвороба Крона). Показані можливості інструментальних та лабораторних методів досліджень. Приділено увагу неінвазивним методам діагностики — визначенню фекального кальпротектину, лактоферину, лізоциму, еластази, мієлопероксидази, α1-антитрипсину. Пошук літератури проводився із застосуванням бази даних PubMed, MedLine, EMBASE.