tbuckley/cabot-search huggingface dataset:
Population-level impact of infant 10-valent pneumococcal conjugate vaccination on adult pneumonia hospitalisations in Finland
Authors: Omar Okasha, Hanna Rinta-Kokko, Arto A Palmu, Esa Ruokokoski, Jukka Jokinen, J Pekka Nuorti
Journal: Thorax (2017)

Introduction Limited data are available on population-level herd effects of infant 10-valent pneumococcal conjugate vaccine (PCV10) programmes on pneumonia. We assessed national trends in pneumococcal and all-cause pneumonia hospitalisations in adults aged ≥18 years, before and after infant PCV10 introduction in 2010. Methods Monthly hospitalisation rates of International Statistical Classification of Diseases, 10th revision (ICD-10)-coded primary discharge diagnoses compatible with pneumonia from 2004–2005 to 2014–2015 were calculated with population denominators from the population register. Trends in pneumonia before and after PCV10 introduction were assessed with interrupted time-series analysis. Rates during the PCV10 period were estimated from adjusted negative binomial regression model and compared with those projected as continuation of the pre-PCV10 trend. All-cause hospitalisations were assessed for control purposes. Results Before PCV10, the all-cause pneumonia rate in adults aged ≥18 years increased annually by 2.4%, followed by a 4.7% annual decline during the PCV10 period. In 2014–2015, the overall all-cause pneumonia hospitalisation rate was 109.3/100 000 (95% CI 96.5 to 121.9) or 15.4% lower than the expected rate. A significant 6.7% decline was seen in persons aged ≥65 years (131.5/100 000), which translates to 1456 fewer pneumonia hospitalisations annually. In comparison, hospitalisations other than pneumonia decreased by 3.5% annually throughout the entire study period. Conclusion These national data suggest that herd protection from infant PCV10 programme has reversed the increasing trend and substantially decreased all-cause pneumonia hospitalisations in adults, particularly the elderly.
GW28-e1143 Biocompatibility and effectiveness evaluation of a new hemostasic embolization agent: thrombin-loaded alginate-calcium microspheres
Authors: Lijun Zhao, Yang Li, Jingjing Rong, Ming Liang, Xuwen Zhang, Jingyang Sun, Li Jun, Dan Liu, Naijing Gao, Fei Li, Xiaozeng Wang, Yaling Han, Wang Shuang
Journal: Journal of the American College of Cardiology (2017)
MYC and MCL1 Cooperatively Promote Chemotherapy-Resistant Breast Cancer Stem Cells via Regulation of Mitochondrial Oxidative Phosphorylation
Authors: Kyung-min Lee, Jennifer M. Giltnane, Justin M. Balko, Luis J. Schwarz, Angel L. Guerrero-Zotano, Katherine E. Hutchinson, Mellissa J. Nixon, Mónica V. Estrada, Violeta Sánchez, Melinda E. Sanders, Taekyu Lee, Henry Gómez, Ana Lluch, J. Alejandro Pérez-Fidalgo, Melissa Magdalene Wolf, Gabriela Andrejeva, Jeffrey C. Rathmell, Stephen W. Fesik, Carlos L. Arteaga
Journal: Cell Metabolism (2017)
Concurrent chemoradiotherapy with 3-weekly versus weekly cisplatin in patients with locoregionally advanced nasopharyngeal carcinoma: A phase 3 multicentre randomised controlled trial (ChiCTR-TRC-12001979).
Authors: Hu Liang, Wei-Xiong Xia, Xing Lv, Rui Sun, Qi Zeng, Si-Wei Li, Hao-Yuan Mo, Fei Han, Dong-Hua Luo, Yan-Fang Ye, Jing Yang, Liang-Ru Ke, Ling Guo, Ming-Yuan Chen, Ka-Jia Cao, Chong Zhao, Hai-Qiang Mai, Chao-Nan Qian, Xiang Guo, Xiang Yanqun
Journal: Journal of Clinical Oncology (2017)

6006 Background: In intensity-modulated radiotherapy (IMRT) era, concurrent chemoradiotherapy (CCRT) with either every three week (ETW) or once a week (OAW) cisplatin is accepted practice for locoregionally advanced nasopharyngeal carcinoma (LANPC). However, ETW and OAW were never prospectively compared in phase 3 clinical trials. This study is to assess the efficacy and toxicity profiles of CCRT with ETW versus OAW schedule of cisplatin. Methods: We conducted an open-label phase 3 multicentre randomised controlled trial in an endemic area. Patients with stage II-IVB NPC were randomly assigned to receive either cisplatin 100 mg/m² every 3 weeks for 2 cycles or cisplatin 40 mg/m² weekly up to 6 cycles concurrently with IMRT. IMRT in both groups was given as 2.19-2.34 Gy per fraction with five daily fractions per week for 6-7 weeks to a total dose of 68-70 Gy to the primary tumor and 62-68 Gy to the involved neck area. The primary endpoint was failure-free survival. Intention-to-treat population was adopted for efficacy analyses. Results: Of the 526 eligible patients, 267 were assigned to OAW arm, and 259 to ETW arm. Two arms were well-balanced in all prognostic factors. No difference was observed in overall tumor response between OAW and ETW (99.6% vs 98.9%, P = 0.624). After a median follow-up of 17.5 months (range 1.6-64.1), estimated 2 year failure-free survival rate was 92% (95% CI 87.7-96.3) in OAW and 88.3% (95% CI 83.2-93.4) in ETW (hazard ratio 1.056, 95% CI 0.58-1.92). The grade 3 or 4 toxicities were similar between two arms, but leucopenia and thrombocytopenia were significantly higher in OAW compared with ETW (24.8% vs 15.9%, P = 0.015 and 5.2% vs 1.1%, P = 0.01, respectively). Stomatitis (35.2% vs 32.6%, P = 0.576), leucopenia and nausea/vomiting (11.2% vs 12.5%, P = 0.684) were the most commonly observed grade 3 or 4 toxicities during both OAW and ETW arms. Conclusions: Weekly regimen of cisplatin as CCRT shows similar treatment efficacy but increased toxic effect of leucopenia and thrombocytopenia compared with 3-weekly schedule in LANPC. Longer follow-up is needed to fully assess prognosis and late toxicities. Clinical trial information: ChiCTR-TRC-12001979.
Elevated Postoperative Endogenous GLP-1 Levels Mediate Effects of Roux-en-Y Gastric Bypass on Neural Responsivity to Food Cues
Authors: Jennifer S. ten Kulve, Dick J. Veltman, Victor E.A. Gerdes, Liselotte van Bloemendaal, Frederik Barkhof, Carolyn F. Deacon, Jens J. Holst, Madeleine L. Drent, Michaela Diamant, Richard G. IJzerman
Journal: Diabetes Care (2017)

OBJECTIVE It has been suggested that weight reduction and improvements in satiety after Roux-en-Y gastric bypass (RYGB) are partly mediated via postoperative neuroendocrine changes. Glucagon-like peptide-1 (GLP-1) is a gut hormone secreted after food ingestion and is associated with appetite and weight reduction, mediated via effects on the central nervous system (CNS). Secretion of GLP-1 is greatly enhanced after RYGB. We hypothesized that postoperative elevated GLP-1 levels contribute to the improved satiety regulation after RYGB via effects on the CNS. RESEARCH DESIGN AND METHODS Effects of the GLP-1 receptor antagonist exendin 9-39 (Ex9-39) and placebo were assessed in 10 women before and after RYGB. We used functional MRI to investigate CNS activation in response to visual food cues (pictures) and gustatory food cues (consumption of chocolate milk), comparing results with Ex9-39 versus placebo before and after RYGB. RESULTS After RYGB, CNS activation was reduced in the rolandic operculum and caudate nucleus in response to viewing food pictures (P = 0.03) and in the insula in response to consumption of palatable food (P = 0.003). GLP-1 levels were significantly elevated postoperatively (P &amp;lt; 0.001). After RYGB, GLP-1 receptor blockade resulted in a larger increase in activation in the caudate nucleus in response to food pictures (P = 0.02) and in the insula in response to palatable food consumption (P = 0.002). CONCLUSIONS We conclude that the effects of RYGB on CNS activation in response to visual and gustatory food cues may be mediated by central effects of GLP-1. Our findings provide further insights into the mechanisms underlying the weight-lowering effects of RYGB.
Surveillance of primary antibiotic resistance of Helicobacter pylori at centres in England and Wales over a six-year period (2000-2005)
Authors: S A Chisholm, E L Teare, K Davies, R J Owen
Journal: Eurosurveillance (2007)

Antibiotic resistance is a key factor in the failure of Helicobacter pylori eradication therapy, yet few sentinel schemes exist to monitor trends in resistance at local, national or international levels. This study aimed, over a six-year period, to monitor resistance levels of H. pylori in England and Wales to the four antibiotics used in its treatment. A total of 1,310 isolates from Gwynedd in north Wales and from mid-Essex in south-east England were collected from 2000 to 2005 and tested for susceptibilities to metronidazole, clarithromycin, amoxicillin and tetracycline. Overall, metronidazole and clarithromycin resistance rates were 28.6% and 8.3% in Gwynedd and significantly higher (36.3%, p=0.0031, and 12.7%, p=0.0112) in mid-Essex. Rates of resistance to metronidazole and clarithromycin increased in both areas over this six-year period. Resistance rates were higher in female compared with male patients (38.1% vs 26.6% for metronidazole, p
GW28-e1052 The mechanism of α7nAChR mediated cholinergic anti-inflammatory pathway in the vagal nerve regulated atrial fibrillation
Authors: Shujuan Zhang, Shudi Zhang, Zixuan Dai, Hongyi Zhao, Yongsheng Qian, Youjing Zhang, Youcheng Wang, Bo He, Yanhong Tang, Xi Wang, Teng Wang, He Huang, Qingyan Zhao, Congxin Huang
Journal: Journal of the American College of Cardiology (2017)
Optimized protocols to determine PD-L1 expression on tumor tissue and cytology samples from non–small cell lung cancer (NSCLC) patients using the 22C3 antibody with various immunohistochemistry (IHC) autostainers
Authors: M. Ilie, S. Khambata-Ford, C. Copie-Bergman, L. Huang, R. Mogg, J. Juco, V. Hofman, P. Hofman
Journal: Annals of Oncology (2017)
GW28-e1003 Krüppel-like factor 14, a coronary artery disease associated transcription factor, inhibits endothelial inflammation via NF-κB signaling pathway
Authors: Wenting Hu, Haocheng Lu, Yanhong Guo, Yanbo Fan, Jifeng Zhang, Daoquan Peng, Yuqing Eugene Chen
Journal: Journal of the American College of Cardiology (2017)
Prediction of long-term outcome subtypes in ARDS: first steps towards personalised medicine in critical care
Authors: Nicola Latronico, Cosetta Minelli, Matthias Eikermann
Journal: Thorax (2017)

In Thorax , Samuel Brown and colleagues present their result on early identification of physical, cognitive and mental health outcome subtypes in patients who survived acute respiratory distress syndrome (ARDS).1 Using data from the ARDSNet Long-Term Outcomes Study, the authors identified a group of 645 patients who had been studied with a comprehensive battery of validated health outcome instruments, which included measures of physical, cognitive and mental health (anxiety, depression and post-traumatic stress disorder), as well as quality of life status, obtained at 6-month follow-up. After splitting the data into derivation and validation datasets, the authors used a data mining approach, weighted network analysis, to identify and validate four outcome subphenotypes. They identified four subtypes: (1) mildly impaired physical and mental health status; (2) moderately impaired physical and mental health status; (3) severely impaired physical and moderately impaired mental health status; and (4) severely impaired physical and mental health status. In each of the four subtypes, one-third of patients suffered a significant decrease from baseline in their health state measured with the EQ-5D or SF36. Separation of outcome subtypes in relation to various instruments of physical and mental health assessment was good, while cognitive function evaluated with Mini-Mental State Examination did not differ significantly across subtypes. Cognitive outcomes remained unrelated to the subtypes defined by physical and mental health outcomes also when using a battery of more detailed cognitive tests available for a subset of patients. This multicentre study confirms that ARDS is associated with long-lasting disability after the resolution of the acute condition: fewer than half of patients were living at home independently at 6 months compared with 91% at baseline. Physical and mental impairments were both severe in one quarter of them, who were mainly female, current smokers …
Synergistic effect of vismodegib and cisplatin in NSCLC models via autophagy
Authors: F. Papaccio, L. Mele, C.M. Della Corte, D. Liccardo, M. La Noce, V. Desiderio, V. Tirino, F. Ciardiello, F. Morgillo
Journal: Annals of Oncology (2017)
Diabetic patients with poor glycaemic control have higher risk of latent TB, study shows
Authors: Sophie Cousins
Journal: BMJ (2017)

Patients with diabetes who have poor glycaemic control are more than twice as likely as the general population to have latent tuberculosis (TB) infection, shows research presented at the 48th Union World Conference on Lung Health in Guadalajara, Mexico.

In a population based study of 4215 people in the United States, researchers found that patients with undiagnosed diabetes were 2.2 times more likely to have latent TB infection than those who did not have diabetes. Patients with diabetes who had high levels of fasting plasma glucose (>130 mg/dL)—a biomarker of poor glycaemic control—were 2.6 times more likely to have …
Impact of tumor location on outcomes in patients with metastatic colorectal cancer (mCRC) treated with regorafenib (REG): An interim analysis from the prospective, observational CORRELATE study.
Authors: Michel Ducreux, Leopold Öhler, Werner Scheithauer, Jean-Philippe Metges, Louis-Marie Dourthe, Jan Willem De Groot, Josef Thaler, Kun-Huei Yeh, Jen-Kou Lin, Alfredo Falcone, Cornelis J. A. Punt, Jan Kalinovsky, Sabine Fiala-Buskies, Andres Cervantes, Juan Manuel O'Connor
Journal: Journal of Clinical Oncology (2017)

3567 Background: The anatomical location of the primary tumor has been associated with outcomes in mCRC, with left-sided (L) tumors having a better prognosis than right-sided (R) tumors and location predicting response to treatment. REG significantly improved overall survival (OS) vs placebo in patients with mCRC who progressed on available treatments in 2 randomized, phase 3 trials (CORRECT, CONCUR). This exploratory analysis evaluated outcomes by primary tumor location in patients with mCRC treated with REG in the CORRELATE study. Methods: CORRELATE is an observational study designed to characterize the safety and effectiveness of REG in unselected patients for whom the decision to treat with REG has been made by the treating physician according to the local health authority label. Primary L tumors were located in the rectum, splenic flexure, recto-sigmoid, descending, or sigmoid colon; R tumors were in the appendix, hepatic flexure, cecum, or ascending colon. OS was analyzed by the Kaplan–Meier method and comparisons were by a 2-sided log-rank test. Results: Primary tumor location was available for 474 patients (L, n = 375 [79%]; R, n = 99 [21%]). Median time from initial diagnosis and from diagnosis of metastatic disease to treatment was slightly longer in L vs R tumors (32 vs 28 months and 25 vs 22 months, respectively). A higher proportion of patients with L vs R tumors, respectively, had prior radiotherapy (34% vs 13%) and a lower proportion had a partial colectomy (40% vs 70%). Best response to prior systemic therapy (partial response + stable disease) was 72% for L tumors and 68% for R tumors with a median duration of treatment of 26 and 22 months, respectively. REG treatment duration was similar in the 2 groups. Median OS (95% CI) was 6.7 months (6.1, 7.7) for L tumors vs 6.3 months (4.9, 8.1) for R tumors (P = 0.3); median progression-free survival (95% CI) was 2.8 months (2.6, 3.0) vs 2.6 months (2.4, 3.0) (P = 0.5), respectively. Conclusions: Interim results from this observational study suggest that OS is similar in patients with R and L tumors treated with REG. Clinical trial information: NCT02042144.
Abstract 16576: Young Bone Marrow Sca-1 Cells Rejuvenate the Aged Heart by Promoting Epithelial-to-Mesenchymal Transition
Authors: Jiao Li, Shu-Hong Li, Richard D Weisel, Shi-Ming Liu, Ren-Ke Li
Journal: Circulation (2016)

Introduction: Reconstitution of aged bone marrow (BM) with young stem cells repopulates cardiac-resident BM-derived progenitor cells and prevents progressive cardiac dysfunction after an MI. Howeve...
Effect of body mass index on metastatic pattern in early breast cancer patients.
Authors: Ozan Yazici, Sercan Aksoy, Mehmet Ali Nahit Sendur, Nuriye Özdemir, Nurullah Zengin, Kadri Altundag
Journal: Journal of Clinical Oncology (2014)

e11553 Background: Obesity is well known risk factor for breast cancer recurrence and poor prognosis. However there is no data available about the effect of obesity on metastatic pattern in early breast cancer patients. Therefore, we aimed to asses the effect of obesity on metastatic pattern in early breast cancer patients. Methods: We retrospectively evaluated the data of 2973 early breast cancer patients who were admitted to Hacettepe University Cancer Institute between years 2002 and 2013. Patients who had BMI values at the time of diagnosis were included into the study. Patients were grouped according to body mass index (BMI) as follows; < 25 kg/m2 (Normal), > 25 – 29 kg/m2 (overweight), ≥ 30 kg/m2 (obese). Metastatic site of patients were grouped in 9 sites; local, contralateral, lymph node, bone, lung, liver, bone marrow, brain and others. For these sites we calculated the site specific disease free survival for each one. The effect of BMI groups on disease free survival (DFS) and overall survival (OS) for each metastatic site was assessed statistically. Results: The median age of patients was 48(min-max:18-92) years. Median BMI at the diagnosis of breast cancer was 27 kg/m2. Median follow up time was 40 months. During this time period 662 (22.3%) patients had recurrence and / or metastasis. Eleven percent of the patients died. DFS and OS were shorter in obese group (p=0.049 and p=0.003, respectively). Site specific DFS for local, contralateral, lymph node, lung, liver, bone marrow and brain sites were not statistically different between BMI groups. Only the bone metastatic site specific DFS was shorter in obese BMI group significantly. 3 –year DFS for bone metastasis were 92% (normal weight), 93% (overweight) and 88% (obese). Conclusions: Obese patients had shorter DFS and OS. Only thebone metastatic site specific DFS was significantly shorter in early breast cancer patients. In conclusion, obese patients may develop earlier bone metastasis compared to normal body weight patients.
Italian nivolumab expanded access programme: real-world results in non-squamous non-small cell lung cancer patients
Authors: F. Grossi, L. Crinò, A. Delmonte, D. Turci, G. Lo Russo, F. De Marinis, H.J. Soto Parra, D. Galetta, F. Cappuzzo, F. Sperandi, M. Tiseo, G. Puppo, F. Roila, M.R. Migliorino, G. Tonini, F. Cognetti, A. Santoro, D. Tassinari, A. Scoppola, E. Cortesi
Journal: Annals of Oncology (2017)
Relative bioavailability (BA) and bioequivalence (BE) study of abiraterone acetate (AA) fine particle (AAFP) with methylprednisolone (MP) and a reference formulation with prednisone (PN) in healthy male subjects.
Authors: Azra Hussaini, Anthony J. Olszanski, Cy Aaron Stein, Bill Bosch, Paul Nemeth
Journal: Journal of Clinical Oncology (2017)

e16538 Background: AA is approved for treatment of metastatic castration-resistant prostate cancer when taken in combination with PN. The originator AA (OAA) formulation is poorly absorbed and exhibits large pharmacokinetic (PK) variability. AAFP is a proprietary formulation (utilizing SoluMatrix Fine-Particle Technology™) that was designed to provide improved BA. In a prior study in healthy subjects, AAFP 500 mg was established as bioequivalent to OAA 1000 mg when given in the fasted state. In this study, AAFP was evaluated in subjects in a fasted state with steady state (SS) MP, an alternative steroid to PN. Methods: Subjects aged 18–50 years were randomized in a crossover design to receive MP (4 mg BID) or PN (5 mg BID) for 12 days in Period 1. On Day 11 of Period 1, subjects given MP received a single dose of AAFP 500 mg (test) and subjects given PN received a single dose of OAA 1000 mg (reference). After a 2-week steroid washout period, subjects received the alternate treatments in Period 2. Results: There were no statistical differences with regard to abiraterone AUC ( P≥0.38) and C max ( P= 0.22) between AAFP 500 mg and OAA 1000 mg (Table). Geometric mean ratio (GMR), a measure of BE, was 95.9% (90% CI: 86.0–106.9%) for AUC 0-∞ , 99.2% (90% CI: 88.7–110.9%) for AUC 0-t , and 116.8% (90% CI: 102.2–133.4%) for C max . GMR of AUC 0-∞ and AUC 0-t , fell within the 80–125% range for BE, and C max 90% CI was just outside the upper limit. The coefficient of variance (CV) for both AUC and C max was smaller for AAFP compared with OAA. Both treatments were safe and well tolerated. Conclusions: AAFP 500 mg with MP gave comparable exposure to OAA 1000 mg with PN with respect to C max and AUC. Less drug exposure variability was observed with AAFP compared with OAA. Reduced PK variability could improve clinical outcomes and warrants further study. [Table: see text]
Intratumoral injection of thermogelling and sustained-release carboplatin-loaded hydrogel simplifies the administration and remains the synergistic effect with radiotherapy for mice gliomas
Authors: Hsiang-Kuang Tony Liang, Xue-Shi Lai, Ming-Feng Wei, Szu-Huai Lu, Wen-Fen Wen, Sung-Hsin Kuo, Chung-Ming Chen, Wen-Yih Isaac Tseng, Feng-Huei Lin
Journal: Biomaterials (2017)
Final DFS results of the SCOT study: An international phase III randomised (1:1) non-inferiority trial comparing 3 versus 6 months of oxaliplatin based adjuvant chemotherapy for colorectal cancer.
Authors: Timothy Iveson, Rachel Kerr, Mark P. Saunders, Niels Henrik Hollander, Josep Tabernero, Andrew Mark Haydon, Bengt Glimelius, Andrea Harkin, Claire Scudder, Kathleen Boyd, Ashita Marie Waterston, Louise C. Medley, Charles Wilson, Richard Ellis, Sharadah Essapen, Amandeep Singh Dhadda, Mark Harrison, Stephen Falk, Sherif Raouf, James Paul
Journal: Journal of Clinical Oncology (2017)

3502 Background: Six months of oxaliplatin-based treatment has been the mainstay of adjuvant chemotherapy for colorectal cancer for the last 13 years. Neurotoxicity from oxaliplatin is cumulative, dose limiting, and potentially irreversible. A shorter duration of treatment would save patients significant toxicity/time and substantially reduce the costs of the drug, its administration, and treatment of adverse effects. Methods: SCOT is a non-inferiority randomised study designed to determine whether 3 months of adjuvant chemotherapy with OxMdG or Xelox (physician/patient choice) in Stage III/high risk Stage II colorectal cancer is as effective as 6 months treatment. Non-inferiority was determined to be a maximum 2.5% fall in 3-year disease-free survival (DFS) on the 3 month arm (from 78% on the 6 month arm) corresponding to a hazard ratio upper limit of 1.13. The study was designed with 90% power at the 2.5% 1-sided level of statistical significance and aimed to recruit 9500 patients to observe 2,750 DFS events (relapses/deaths/new colorectal cancers). Analysis used a Cox model adjusted for study minimisation factors. Results: 6088 patients (60% male, median age 65) with Stage III/high risk Stage II cancers of the colon or rectum were randomised between 27th March 2008 and 29th November 2013. The arms were balanced for clinical and pathological factors. Intended treatment was OxMdG for 1981 and Xelox for 4107 patients. There were 1469 DFS events (734 in 3 month arm and 735 in 6 month arm) giving the study 66% power. 3 year DFS was 76.8% (se = .8%) for the 3 month arm and 77.4% (se = .8%) for the 6 month arm (HR 1.008, 95% CI 0.910-1.117, test for non-inferiority p = 0.014). Non-inferiority appeared stronger for Xelox than OxMdG (test for heterogeneity, p = .059). Results will be shown broken down by stage, site, age, gender and achieved duration of treatment. Conclusions: The SCOT study has shown that 3 months adjuvant treatment is not inferior to 6 months treatment. However the SCOT study is part of the IDEA consortium and the results from the 6 studies in the IDEA consortium addressing the same duration question will also be presented at ASCO 2017. Clinical trial information: ISRCTN59757862.