tbuckley/cabot-search huggingface dataset:
Reasons for Electronic Cigarette Use Among Middle and High School Students — National Youth Tobacco Survey, United States, 2016
Authors: James Tsai, Kimp Walton, Blair N. Coleman, Saida R. Sharapova, Sarah E. Johnson, Sara M. Kennedy, Ralph S. Caraballo
Journal: MMWR Morbidity and Mortality Weekly Report (2018)

Electronic cigarettes (e-cigarettes) were the most commonly used tobacco product among U.S. middle school and high school students in 2016 (1). CDC and the Food and Drug Administration (FDA) analyzed data from the 2016 National Youth Tobacco Survey (NYTS) to assess self-reported reasons for e-cigarette use among U.S. middle school (grades 6-8) and high school (grades 9-12) student e-cigarette users. Among students who reported ever using e-cigarettes in 2016, the most commonly selected reasons for use were 1) use by "friend or family member" (39.0%); 2) availability of "flavors such as mint, candy, fruit, or chocolate" (31.0%); and 3) the belief that "they are less harmful than other forms of tobacco such as cigarettes" (17.1%). The least commonly selected reasons were 1) "they are easier to get than other tobacco products, such as cigarettes" (4.8%); 2) "they cost less than other tobacco products such as cigarettes" (3.2%); and 3) "famous people on TV or in movies use them" (1.5%). Availability of flavors as a reason for use was more commonly selected by high school users (32.3%) than by middle school users (26.8%). Efforts to prevent middle school and high school students from initiating the use of any tobacco product, including e-cigarettes, are important to reduce tobacco product use among U.S. youths (2).
Prostate-Specific Membrane Antigen Positron Emission Tomography/Computed Tomography in Locally Advanced, Recurrent, and Metastatic Prostate Cancer
Authors: Marlon Perera, Declan Murphy, Nathan Lawrentschuk
Journal: JAMA Oncology (2018)

To the Editor We read with great interest the recent article by Lindenberg et al.1 We commend the authors on a timely and comprehensive review in this important topic. However, there are several inconsistencies and inaccuracies that we believe necessitate clarification.
NHS’s “Luddite” approach to IT hinders training, academy says
Authors: Tom Moberly
Journal: BMJ (2014)

The NHS’s “Luddite” approach to technology is making junior doctors’ lives “incredibly difficult,” the head of the Academy of Medical Royal Colleges believes.

Terence Stephenson said that the NHS has been “extraordinarily Luddite” in its use of IT. “What really makes trainee doctors’ jobs incredibly difficult is that they are trying to practise 21st century medicine in a 20th century health service,” he said.

Stephenson …
DOSE DEPENDENT EFFECT OF INTRAVENOUS FENTANYL ADMINISTRATION ON TICAGRELOR ABSORPTION AND PLATELET INHIBITION IN PATIENTS RECEIVING PERCUTANEOUS CORONARY INTERVENTION: A SECONDARY-ANALYSIS OF THE PACIFY RANDOMIZED CLINICAL TRIAL
Authors: John W. McEvoy, Rakesh R. Goli, Khalil Ibrahim, Rohan Shah, Thomas S. Kickler, William A. Clarke, Steven Schulman
Journal: Journal of the American College of Cardiology (2018)
N -trimethyl chitosan nanoparticles and CSKSSDYQC peptide: N -trimethyl chitosan conjugates enhance the oral bioavailability of gemcitabine to treat breast cancer
Authors: Guanyu Chen, Darren Svirskis, Weiyue Lu, Man Ying, Yuan Huang, Jingyuan Wen
Journal: Journal of Controlled Release (2018)
Association of somatic mutational burden with depression and anxiety in patients with metastatic urothelial cancer (mUC).
Authors: Cristiane Decat Bergerot, Karen L. Clark, Paulo Gustavo Bergerot, Kimlin Tan Ashing, Andrew W Hahn, Richard Obenchain, Nazli Dizman, Joann Hsu, Errol James Philip, Matthew J. Loscalzo, Sumanta K. Pal
Journal: Journal of Clinical Oncology (2018)

471 Background: Depression and anxiety are highly prevalent in patients (pts) with genitourinary tumors, including UC (Yang et al PLoS ONE 2016). Given that mUC has a high rate of somatic genomic alterations (GAs), we sought to determine if tumor mutational burden (TMB) or specific alterations were related to the incidence of these psychiatric disorders. Methods: From a single institution, we identified consecutive pts with mUC who had comprehensive genomic profiling done in the course of routine clinical care. In a CLIA-certified laboratory, DNA was extracted from 40 microns of FFPE sections. Hybridization-captured, adaptor ligation based libraries were used to a mean coverage depth of 718X for up to 315 cancer-related genes plus introns from up to 28 genes frequently rearranged in cancer. TMB was estimated based on the cumulative number of GAs. ICD-9 diagnoses corresponding to adjustment disorder (309.28), anxiety (300) and depression (311) were derived from detailed chart review, including review of established diagnoses and medication history. Results: A total of 43 pts (74.4% M / 25.6% F) were assessed with a median age of 65.5 (range, 49-81). Formal diagnoses of adjustment disorder, anxiety and depression were noted in 16.3%, 9.3% and 7.0% pts, respectively. An average of 6.3 GAs/pt (range, 0-14) were observed over the entire cohort. The rate of GA was higher in pts with anxiety vs adjustment disorder or depression (8.5 vs 6.8 or 4.0, P=0.01). No significant difference was observed in adjustment disorder or depression based on the frequency of GAs. GAs in BAP1, PIK3CB, NOTCH1, ALK, CDH1 and FANCC were noted to be associated with higher rates of anxiety (P=0.02). Similarly, GAs in FGFR1 was noted to be associated with higher rates of depression (P=0.002) and in CHEK2 in depression and adjustment disorder (P=0.03). Conclusions: Our study represents the first pyschogenomic analysis of pts with mUC. While higher TMB has been associated with favorable prognosis (Isharwal et al EU Focus 2017), we paradoxically found this to be related to higher rates of anxiety. Our findings suggest that genomically selected subsets of patients may be prime candidates for early psychosocial screening and intervention.
Do the benefits of folic acid fortification outweigh the risk of masking vitamin B<sub>12</sub>deficiency?
Authors: James L Mills, Anne M Molloy, Edward H Reynolds
Journal: BMJ (2018)

Adding folate to cereals can prevent neural tube defects and other health problems, say <b>James Mills</b> and <b>Anne Molloy</b>, but <b>Edward Reynolds</b> is concerned that prolonged excessive folate risks harm unless vitamin B<sub>12</sub> is also supplemented
Doctors’ concerns over social media use continue to rise
Authors: Abi Rimmer
Journal: BMJ (2014)

The number of doctors calling with concerns about social media has increased by 74% since 2013, the Medical and Dental Defence Union of Scotland (MDDUS) has said. 

The organisation said that, although the rise could be partly due to an increase in its membership, it had received four times as many social media related calls in 2014 as in 2011.

Separately, the Medical Defence Union …
Evaluation of systemic inflammation based prognostic scores in patients with advanced oesophageal cancer receiving palliative radiotherapy.
Authors: Ross Dolan, Elliot Tilling, Chia Y Kong, Nicholas James MacLeod, Stephen Thomas McSorley, James Hugh Park, Paul Glen, Paul G. Horgan, Barry Laird, Donald C McMillan
Journal: Journal of Clinical Oncology (2018)

21 Background: The presence of a systemic inflammatory response (SIR) in patients with advanced cancer is an increasingly recognised prognostic domain and is commonly assessed by the Glasgow Prognostic Score (GPS) and modified Glasgow Prognostic Score (mGPS). However, little work has been carried out to evaluate their role in palliative radiotherapy. The aim of the present study was to compare the prognostic value of the GPS/mGPS in patients with advanced oesophageal cancer receiving palliative radiotherapy. Methods: Those patients receiving palliative radiotherapy for oesophageal cancer between 2010 and 2015 were examined (n=194). After exclusions the following demographic data was recorded sex, age, indication for radiotherapy, time from treatment to death/last clinic visit, medical comorbidities, tumour and radiotherapy location/dose, CRP, albumin, and differential blood counts. GPS, mGPS, NLR, PLR and LMR were all calculated and Cox regression analysis carried out in SPSS. Results: Patients who had undergone non-oesophageal/neoadjuvant radiotherapy (n=2) or died within 30 days of treatment administration were excluded (n=22). Of the remaining 170 analysed, 112 (66%) were male and the median age was 72 (Range: 43-91). The most common clinical indications for radiotherapy were dysphagia (n=142), weight loss (n=81) and pain (n=50). Medical comorbidities varied with the most common being hypertension (n=83), ischaemic heart disease (n=46) and COPD (n=42). At the time of analysis, 170 (100%) of the patients were dead with median survival of 6 months (Range: 1-81 month). On univariate six month cancer specific survival analysis, TNM stage (p=0.028), GPS (p&lt;0.001) and mGPS (p&lt;0.001) were significantly associated with poor survival. On multivariate analysis of the significant variables, only mGPS (HR: 2.28, 95%CI 1.29-4.01, p=0.004) and TNM stage (HR: 1.71 95%CI 1.09-2.69, p=0.020) remained independently associated with survival. Conclusions: In the palliative radiotherapy setting, systemic inflammation based scores (GPS/mGPS) had prognostic value and the mGPS had independent prognostic value.
Safety and efficacy of nivolumab in metastatic renal cell carcinoma (mRCC): Results from the NIVOREN GETUG-AFU 26 study.
Authors: Laurence Albiges, Sylvie Negrier, Cécile Dalban, Gwenaelle Gravis, Christine Chevreau, Stephane Oudard, Brigitte Laguerre, Philippe Barthelemy, Delphine Borchiellini, Marine Gross-Goupil, Lionnel Geoffrois, Meryem Brihoum, Bernard Escudier
Journal: Journal of Clinical Oncology (2018)

577 Background: Nivolumab (N) has been approved for the treatment of mRCC after failure of 1 or 2 tyrosine kinase inhibitors (TKI) based on the results of Checkmate 025 study. Right after approval, we initiated the NIVOREN GETUG-AFU 26 study (NCT03013335), a French multicenter prospective study to evaluate safety and efficacy of N in a “real world setting”. Methods: Patients (pts) with clear cell mRCC could be enrolled if they had received at least one TKI. Compared with the pivotal trial, inclusion criteria allowed patients with more than 2 previous lines of treatment, including previous mTOR inhibitors, ECOG PS 2, asymptomatic brain metastases (BM) or impaired renal function. The primary objective of the study was the safety of N, efficacy being the main secondary objective. Between February 2016 and June 2017, 729 pts have been enrolled. We report the results from the first 528 pts. Results: All pts had clear cell mRCC, median age was 64, 77.2% were male. ECOG PS was &gt; 1 in 73 pts (14.7%), 27.5% pts had received prior everolimus, 29.7% pts had received more than 2 previous lines, IMDC risk groups were 19%/54.9%/26.1% for good/intermediate and poor risk respectively; 69 (14%) pts had BM at screening. With a median follow up of 13.1 months, median duration of treatment was 4.1 months [0-15.6], with 31.4% of pts still on therapy. Treatment discontinuation due to adverse event (AE) occurred in (48) 13.3% pts . 64 serious related AE have been reported in 52 pts (9.9%) including 7 renal failures and 6 pneumonitis. Median PFS was 4.4 months 95%CI[3;4.6] . At the time of this analysis, 170 pts have died and 12 months OS rate was 66.4% 95%CI[ 61.7; 70.7]. In subgroups analysis, ECOG-PS &gt; 1 (Hazard Ratio (HR) = 2.450 [1.704;3.523]), more than 2 previous lines (HR = 1.442 [1.059;1.963]) and prior use of everolimus (HR = 1.704 [1.250;2.322]) were associated with reduced OS in univariate analysis. Conclusions: We report the first analysis of the largest prospective real world setting study of N in mRCC. NIVOREN study demonstrates that N safety and efficacy in a “real world” prospective study are comparable to the pivotal study. Clinical trial information: NCT03013335.
Abstract P5-07-09: Identification of miRNA biomarkers for early diagnosis of basal-like breast cancer
Authors: CK Wong, S Thiagalingam
Journal: Cancer Research (2018)

Abstract The routine screening for breast cancer relies primarily on imaging techniques such as mammography and ultrasonography, but it is often not sensitive enough for early detection and requires complementary approaches. Recent studies suggest that microRNAs (miRNAs) could be used as biomarkers for breast cancer due to its relative stability in archived formalin-fixed tissues as well as in bodily fluids. However, the identity of unique miRNAs that could discriminate proliferative and malignant states of the disease has remained elusive. Since TGFβ-induced epithelial-mesenchymal transition (EMT) represents a critical step during tumor progression and intravasation, studying the cancer cell at the mesenchymal state and its precursor could help to identify these critical diagnostic biomarkers. To identify novel biomarkers for early detection, we performed miRNA gene expression profiling of an established basal-like breast cancer (BLBC) model system with and without disruption of TGFβ signaling. We have identified a panel of miRNAs, including miR-210-3p, that are highly expressed in the motile, mesenchymal stage, which could potentially be used as markers in liquid biopsies for early detection of invasive BLBC. Conversely, we also found some miRNAs, including miR-200c and miR-4417, highly expressed in the noninvasive, epithelial stage. Transient overexpression of miR-4417 in mesenchymal BLBC cells was able to suppress migration and mammosphere formation in vitro, suggesting that it could block progression of BLBC, a disease highly prevalent in young African-American women and lacks targeted therapy. Citation Format: Wong CK, Thiagalingam S. Identification of miRNA biomarkers for early diagnosis of basal-like breast cancer [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P5-07-09.
CHANGES IN AORTOMITRAL ANNULAR ANGLE AFTER TRANSCATHETER AORTIC VALVE REPLACEMENT: IMPLICATIONS FOR TRANSCATHETER MITRAL VALVE REPLACEMENT?
Authors: Gilbert Hin-Lung Tang, Mohammed Hasan Khan, Syed Zaid, Abdallah Sanaani, Tanya Dutta, Mala Sharma, Angelica Poniros, Hasan Ahmad, Ryan Kaple, Cenap Undemir, Martin Cohen, Steven Lansman
Journal: Journal of the American College of Cardiology (2018)
Single center validation of neutrophil-to-lymphocyte ratio in localized and metastatic clear cell renal cell carcinoma.
Authors: Kevin Richard Melnick, Dattatraya H Patil, Amir Ishaq Khan, Frances Y Kim, Mersiha Torlak, Mehmet Asim Bilen, Omer Kucuk, Bradley Curtis Carthon, Christopher Paul Filson, Kenneth Ogan, Haydn T. Kissick, Viraj A. Master
Journal: Journal of Clinical Oncology (2018)

696 Background: The neutrophil-to-lymphocyte ratio (NLR) has been evaluated as a serum marker of inflammation and oncologic prognosis. In renal cell carcinoma (RCC), a higher preoperative NLR is associated with aggressive clinicopathologic features and is an independent predictor of poor survival. This study builds upon our institution’s prior work with the NLR in metastatic RCC and examines a larger validation cohort that includes localized disease. It also compares the predictive power of the NLR to established kidney cancer prognostic scores. Methods: Our kidney cancer database provided patients with clear cell RCC who underwent nephrectomy from January 2001 to June 2017 and had a documented preoperative NLR within 15 days prior to surgery. The optimal threshold of NLR was determined using receiver operating characteristic (ROC) curve and sensitivity-specificity trade-off analysis. Kaplan-Meier curves and logistic regression analysis were performed to assess the significance and independence of preoperative NLR in predicting OS. Finally, the prognostic ability of NLR was compared to current prognostic scores through chi-square analysis of their respective c-indices. Results: The 441 patient cohort was comprised of 361 patients with localized and/or regional disease and 80 patients with distant metastases. NLR values among all participants ranged from 0.4 to 74.0 (median 3.1). ROC analysis defined an optimal preoperative NLR threshold of 3.5. On multivariate analysis, after adjusting for clinicopathologic features and distant metastatic disease, a NLR ≥ 3.5 was found to be a significant and independent predictor of overall survival (HR = 1.41, 95% CI 1.05-1.91 &amp; p value = 0.024). Our data also revealed no statistically significant difference between the c-indices of NLR and the UISS, SSIGN, or Leibovich scores in predicting survival. Conclusions: In our validation cohort of patients with both metastatic and non-metastatic clear cell RCC, our data show that a preoperative NLR ≥ 3.5 is a significant and independent predictor of overall survival in patients undergoing nephrectomy and is comparable to other established prognostic tools in RCC.
Immunological correlates of response to immune checkpoint inhibitors (ICI) in metastatic urothelial carcinoma (mUC) patients (pts).
Authors: Alice Tzeng, C. Marcela Diaz-Montero, Patricia A. Rayman, Jin Sub Kim, Paul G Pavicic, James Finke, Pedro C. Barata, Marcelo Lamenza, Sarah Devonshire, Kim Schach, Hamid Emamekhoo, Marc S. Ernstoff, Christopher J. Hoimes, Brian I. Rini, Jorge A. Garcia, Timothy D. Gilligan, Moshe Chaim Ornstein, Petros Grivas
Journal: Journal of Clinical Oncology (2018)

454 Background: Identification of biomarkers predictive of response to ICI could help guide treatment (tx) decisions. We assessed the correlation between PD1/PDL1 expression in key immunomodulatory subsets (myeloid-derived suppressor cells [MDSC]; CD8 + T cells) and tx response in mUC pts treated with ICI. Methods: Serial peripheral blood samples were collected from mUC pts treated with ICI. Flow cytometry was used to quantify PD1/PDL1 expression in MDSC (CD33 + HLADR − ) and CD8 + T cells (CD8 + CD4 − ) from live peripheral blood mononuclear cells. MDSC were subdivided into monocytic (M)-MDSC (CD14 + CD15 − ), polymorphonuclear (PMN)-MDSC (CD14 − CD15 + ), and immature (I)-MDSC (CD14 − CD15 − ). Mixed-model regression and Wilcoxon rank-sum tests were performed to assess post-ICI changes in immune marker expression and identify correlations between PD1/PDL1 expression and best overall response (BOR) to ICI. Results: Of 36 ICI-treated pts with ≥2 blood samples, 24 received anti-PDL1 (22 atezolizumab/2 avelumab; [A]) and 12 received anti-PD1 (pembrolizumab [P]). 78% were men, median age 69 (46–81), 28% never smokers, 19% had prior intravesical BCG, 39% prior neoadjuvant chemotherapy, and 64% prior cystectomy. BOR to ICI included 3 PR/14 SD/7 PD (A) and 1 CR/2 PR/6 SD/3 PD (P). Successive doses of A correlated with decreased %PDL1 + M-MDSC (mean change −5.26/dose; p = 0.009), while those of P correlated with decreased %PD1 + M- and I- MDSC (mean change −1.55 and −1.14/dose; p = 0.04 and 0.02, respectively). Though pre-tx %PD1 + CD8 + T cells did not predict BOR, greater PD1 expression by CD8 + T cells within 12 weeks after ICI initiation correlated with BOR (Table). Conclusions: ICI tx correlated with distinct changes in PD1/PDL1 expression by specific peripheral immune cell subsets. Responders to ICI had higher % of PD1 + CD8 + T cells after ICI than non-responders, though pre-tx % were comparable between groups. Further validation of these and other potential blood/tissue biomarkers is ongoing. [Table: see text]
Association of p27 and Cyclin D1 Expression and Benefit from Adjuvant Trastuzumab Treatment in HER2-Positive Early Breast Cancer: A TransHERA Study
Authors: Martin Filipits, Urania Dafni, Michael Gnant, Varvara Polydoropoulou, Margaret Hills, Astrid Kiermaier, Evandro de Azambuja, Denis Larsimont, Federico Rojo, Giuseppe Viale, Masakazu Toi, Nadia Harbeck, Kathleen I. Prichard, Richard D. Gelber, Phuong Dinh, Dimitrios Zardavas, Brian Leyland-Jones, Martine J. Piccart-Gebhart, Mitch Dowsett
Journal: Clinical Cancer Research (2018)

Purpose: To assess the prognostic and predictive value of selected biomarkers involved in cell-cycle regulation or proliferation in patients with HER2-positive early breast cancer.Experimental Design: Protein expression of TOP2A, Ki67, cyclin D1, and p27 was immunohistochemically determined in tissue microarrays of surgical specimens from 862 patients randomized to trastuzumab (1 or 2 years; N = 561) and observation (N = 301) arms of the HERA trial. The primary analysis endpoint was disease-free survival (DFS). Biomarkers were examined as continuous or categorical variables (predefined cutoffs). Interaction terms between biomarkers and treatment were assessed in multivariate Cox models adjusted for variables of clinical interest.Results: A significant interaction was detected between p27 and treatment (adjusted P = 0.0049). Trastuzumab effect was significant in the p27-low subgroup (≤70% p27-positive tumor cells; N = 318). HR Comb Trast vs. Obs 0.44, 95% CI, 0.29-0.65 (P < 0.001). No trastuzumab effect was observed in the p27-high subgroup N = 435; HR Comb Trast vs. Obs 0.97, 95% CI, 0.66-1.44, P = 0.89), indicating that these patients derived little or no benefit from trastuzumab treatment. A prognostic effect of p27 on DFS was observed, with p27-high patients experiencing half the hazard of a DFS event compared with low ones (HR p27 High vs. Low 0.49, 95% CI, 0.32-0.75). TOP2A, Ki67, and cyclin D1, as categorical variables were not predictive, whereas cyclin D1 as continuous variable was predictive of trastuzumab benefit.Conclusions: In TransHERA, patients with HER2-positive early breast cancer with low p27 expression in their tumors benefited from trastuzumab treatment, whereas patients with high p27 expression did not. Clin Cancer Res; 24(13); 3079-86. ©2018 AACR.