tbuckley/cabot-search huggingface dataset:
Baseline frequency of brain metastases and outcomes with multikinase inhibitor therapy in patients with <i>RET</i>-rearranged lung cancers.
Authors: Alexander E. Drilon, Thomas Filleron, Isabella Bergagnini, Julie Milia, Vaios Hatzoglou, Vamsidhar Velcheti, Benjamin Besse, Tony Mok, Mark M. Awad, Juergen Wolf, David P. Carbone, D. Ross Camidge, Gregory J. Riely, Nir Peled, Julien Mazieres, Mark G. Kris, Oliver Gautschi
Journal: Journal of Clinical Oncology (2017)

9069 Background: In phase 2 trials, multikinase inhibitors with activity against RET are active in a subset of patients (pts) with RET-rearranged lung cancers (response rate of 28%, phase 2 study of cabozantinib; Drilon et al Lancet Oncol 2016). Data on the incidence of brain metastases and outcomes with multikinase inhibitor therapy in pts with intracranial disease have not previously been reported. Methods: The frequency of brain metastases at diagnosis of metastatic disease was evaluated in pts accrued to a global registry of RET-rearranged lung cancer pts identified by a multicenter network of thoracic oncologists (Gautschi et al JCO 2017). A proportion of pts were treated with 9 multikinase inhibitors including cabozantinib, vandetanib, lenvatinib, alectinib, and ponatinib. On a prospective phase 2 trial (NCT01639508), patients with asymptomatic brain metastases were eligible. Intracranial response to cabozantinib (RECIST v1.1) was evaluated in an exploratory fashion. Results: 114 registry pts with RET-rearranged lung cancers had metastatic disease at diagnosis. Baseline brain metastases were identified in 27% (95%CI 18-34%, n = 20/75) of pts with available information. No differences (p &gt; 0.05) in age, smoking history, or upstream fusion partner ( KIF5B100% vs 84%, with and without brain metastases, p = 0.53) were noted. In 37 pts treated with multikinase inhibitors with activity against RET, there were no significant differences in median PFS (2.1 vs 2.1 months, p = 0.41) or median OS (3.9 vs 7.0 months, p = 0.10) in pts with (n = 10) and without (n = 27) brain metastases. On a phase 2 trial of cabozantinib, baseline untreated brain metastases were present in 5 pts. Intracranial disease control (stable disease; -34% and -1% in 2 pts with measurable disease) was achieved in 4 of 4 pts with measurable or evaluable intracranial disease with time to treatment discontinuation ranging from 2.4 months to 2.9 years. Conclusions: Brain metastases are present in a substantial proportion of RET-rearranged lung cancer pts. Intracranial disease control can be achieved in select pts by a multikinase inhibitor. Novel RET-directed targeted therapy strategies should address intracranial disease. Clinical trial information: NCT01639508.
High-dose methotrexate for metastatic breast cancer to the central nervous system: A single-institution review of 46 patients.
Authors: Margaret A. Schwartz
Journal: Journal of Clinical Oncology (2014)

1079 Background: The prognosis for patients with metastatic breast cancer to the central nervous system (CNS) is poor. Methotrexate (MTX) is an active agent in the treatment of breast cancer and penetrates the CNS at high doses and rapid rate of infusion. Methods: We performed an IRB approved retrospective review of patients treated at Northwestern from 8/1/2003 to 12/31/2013. Demographic data collected included date of diagnosis, time to CNS metastases, Karnofsky Performance Status, HER-2 and hormone status, radiographic and/or cytologic response to MTX, progression-free survival (PFS) and overall survival (OS). Results: Forty-six patients met criteria for inclusion. All patients were women with a median age of 49 (range 28-80) and average KPS of 70 (range: 20-100). Median number of doses was 4 (range 1-22), dosed at 3.5 gm/m2. The median PFS and OS were 3.4 and 4.1 months (m). Patients with ER/PR- disease had median PFS/OS of 5.2m/8.7m (HER2-) and 1.2m/3.0m (HER2 +). Patients with ER/PR+ disease had median PFS/OS of 3.4m/4.1m (HER2 -) and 3.4m/3.8m (HER2 +). When response was evaluated based on KPS, PFS/OS rates are 6.8m/15.2m for patients with KPS≥70. Patients with KPS<70 had PFS/OS rates of 3.2m/4.0m. Six patients are alive after completing MTX treatment and continue systemic therapies. There were 34 patients with scans for treatment evaluation: 1 complete response, 3 partial responses, and 16 patients had stable disease. Most common toxicities were anemia, hypokalemia, mucositis, transient elevations in liver enzymes, and thrombocytopenia. Conclusions: High-dose intravenous methotrexate remains a treatment option for patients with CNS metastases of breast cancer. Patients with ER/PR negative disease trended toward better PFS and OS. Patients with KPS less than 70 may not warrant treatment given shorter survival.
Inhibition of TRF1 Telomere Protein Impairs Tumor Initiation and Progression in Glioblastoma Mouse Models and Patient-Derived Xenografts
Authors: Leire Bejarano, Alberto J. Schuhmacher, Marinela Méndez, Diego Megías, Carmen Blanco-Aparicio, Sonia Martínez, Joaquín Pastor, Massimo Squatrito, Maria A. Blasco
Journal: Cancer Cell (2017)
Abstract 13687: Appropriate Qt Correction Could Limit Unnecessary Avoidance of Drugs With a Risk of Tdp in Clinical Practice
Authors: Bert Vandenberk, Eline Vandael, Joris Vandenberghe, Isabelle Spriet, Veerle Foulon, Rik Willems
Journal: Circulation (2014)

Introduction:  Risk monitoring of QT-prolonging drugs to avoid ventricular arrhythmias is mainly based on monitoring Bazett corrected QT-interval. However, there is a known undercorrection for high heart rates and no correction for ventricular conduction defects.   Methods:  In a point prevalence study we collected 212 electrocardiograms before the first prescription of haloperidol. We compared 6 correction formulas (Bazett, Fridericia, Rautaharju, Framingham, Nomogram (range from 40-120 bpm) and Hodges). QTc-intervals  500ms a high risk. The formulas were compared using QTc/RR linear regression slopes (QTc= BxRR+Cst), differences were compared using two-sided t-tests and chi 2  analysis.   Results:  Mean age of the patients was 73±15 years and 127 (60%) were male. Sinus rhythm was present in 167 (79%), 39 (18%) were in AF, 6 (3%) had pacemaker rhythm. Median HR was 81 bpm (range 47 - 153). Ventricular conduction defects were present in 31 (15%). QTcH showed overall the best rate adjustment (B=0.015±0.011), followed by QTcR (B=0.032±0.010) and QTcN (B=0.034±0.012). All correction formulas had significant shorter QTc values compared to QTcB (QTcH 429±29ms vs QTcB 449±33ms, p 2  test p   Conclusions:  Performing QTc prolongation risk analysis only based on Bazett’s correction formula could lead to false positive drug alert generation by automatic algorithms incorporated in electronic medical records and to unnecessary avoidance of clinically indicated drugs. The use of Hodges or Rautaharju’s (in case of ventricular conduction defects) linear correction formulas should be recommended.
Prognostic role of expression levels of FABP3 and AKR1B10 genes in adenocarcinoma stage I patients.
Authors: Vienna Ludovini, Annamaria Siggillino, Fortunato Bianconi, Lorenza Pistola, Rita Chiari, Giulio Metro, Francesca Romana Tofanetti, Jacopo Vannucci, Stefano Treggiari, Guido Bellezza, Angelo Sidoni, Francesco Puma, Lucio Crino
Journal: Journal of Clinical Oncology (2015)

7547 Background: In resected lung cancer, no reliable clinical or molecular predictors are currently available for identifying patients with high risk for recurrent disease. In a previous study, we selected 5 genes up-regulated and 4 genes down-regulated which were predictive for clustering adenocarcinoma (ADC) patients in early relapse (ER) and non relapse (NR) using Affimetrix human microarray HG-U133Plus 2.0. Here we validate our results using an independent cohort of patients with lung ADC stage I to identify novel genes involved in the risk of ER compared to NR disease. Methods: From tissue banking of 180 consecutive resected NSCLC patients, we selected frozen specimens of ADC with corresponding normal lung of stage I patients. Quantification of mRNA expression levels of 9 genes (5 up-regulated: CLCA2, FABP3, H19, TFPI2, AKR1B10 and 4 down-regulated: CYP3A5, ALDH3A1, SCGB3A2, SCGB1A1), were analyzed by real-time one-step RT-PCR using QuantiFast assay (Qiagen).The gene expression levels and their association with relapsed disease and molecular features were assessed by t-test and Fisher’s exact test, respectively. The logistic regression model was used for multivariate analysis. Results: Seventy-nine patients were evaluable, 23% of which had an ER. The mean expression levels of CYP3A5 and SCGB3A2 was down-regulated in ER respect to NR (0.31 vs 1.12; 0.80 vs 2.07 respectively). P53 mutations were associated with smoking history (p = 0.01) and had a tendency to significance with FABP3 (p = 0.07). In the univariate analysis the mean expression levels of AKR1B10 and FABP3 were correlated with a worse disease free survival (DFS) (p = 0.024 and p = 0.017 respectively). In the multivariate analysis the mean expression levels of all genes showed a tendency to predict the ER in the overall population (p = 0.06). The multivariate analysis adjusted for age, smoking, stage high AKR1B10 and FABP3 expression levels maintain their prognostic effect for a poor DFS (p = 0.003). Conclusions: It is possible to define through gene expression, a characteristic gene profiling of ER patients. Such features may have important implications for future targeted therapies. This study was supported by Italian Association for Cancer Research (AIRC).
Förster Resonance Energy Transfer-Based Dual-Modal Theranostic Nanoprobe for <i>In Situ</i> Visualization of Cancer Photothermal Therapy
Authors: Dehong Hu, Zonghai Sheng, Mingting Zhu, Xiaobing Wang, Fei Yan, Chengbo Liu, Liang Song, Ming Qian, Xin Liu, Hairong Zheng
Journal: Theranostics (2017)

The visualization of the treatment process in situ could facilitate to accurately monitor cancer photothermal therapy (PTT), and dramatically decrease the risk of thermal damage to normal cells and tissues, which represents a major challenge for cancer precision therapy. Herein, we prepare theranostic nanoprobes (NPs) for Förster resonance energy transfer (FRET)-based dual-modal imaging-guided cancer PTT, and clear visualization of the therapeutic process. The FRET-based theranostic NPs exhibit high FRET efficiency (88.2%), good colloidal stability, and tumor-targeting ability. Tumor tissue and surrounding blood vessels are visualized clearly by FRET-based NIR fluorescence imaging with a high signal-to-background ratio (14.5) and photoacoustic imaging with an excellent resolution at 24 h post injection of NPs. Under the guidance of dual-modal imaging, the NPs-induced photothermal effect selectively destructs cancer cells, simultaneously decreasing the FRET efficiency and leading to fluorescence and photoacoustic signal changes. The sensitive self-feedback process enables the in situ visualization of therapeutic process and precision guidance of in vivo cancer PTT. A high therapeutic efficacy and minimum side effects are achieved in C6 tumor-bearing nude mice, holding great promise for precision therapy and cancer theranostics.
L'évolution internationale des sérotypes de salmonelle de 1998 à 2003 - un rapport du réseau de surveillance international Enter-net
Authors: I. S.T. Fisher
Journal: Eurosurveillance (2004)

L'un des objectifs de toute activite de surveillance est de suivre l'evolution des infections. Depuis 1993, le reseau international de surveillance des infections enteriques humaines, Enter-net, recueille et publie des donnees sur les infections humaines a salmonelles confirmees microbiologiquement. Le nombre de cas identifies a augmente au milieu des annees 1990, avec un pic en 1997. L'article suivant decrit la diminution, apres ce pic, des serotypes de salmonelles notifies entre 1998 et 2003 par les laboratoires nationaux de reference participant au reseau de surveillance Enter-net. Au cours de cette periode, le nombre total de cas humains a chute de 220 698 a 142 891. En depit de cette baisse, les salmonelloses restent une source importante de morbidite chez l'homme.
Abstract 16922: Impact of Neighborhood Socio-economic Status on Bystander Cardiopulmonary Resuscitation in Paris
Authors: Benjamin Dahan, Patricia Jabre, Nicole Karam, Renaud Misslin, Muriel Tafflet, Wulfran Bougouin, Daniel Jost, Frankie Beganton, Eloi Marijon, Xavier Jouven
Journal: Circulation (2016)

Introduction:  There is no European data on the impact of neighborhood socio-economic status (SES) on Out-of-Hospital Cardiac Arrest (OHCA) bystander CPR. This study aims to analyze, based on a robust deprivation index, neighborhood SES impact on bystander CPR.   Hypothesis:  We hypothesize that OHCA victims in deprived area could be less likely to beneficiate a bystander CPR.   Methods:  Data of all OHCA were collected prospectively between 2000 and 2010, in Paris. A geographical neighborhood unit was assigned to each case. Median household income, blue-collar workers rate, unemployment rate and adults without high school diploma rate were selected as SES characteristics and neighborhoods were classified in low SES neighborhood or medium- high SES neighborhood. We analyzed the relationship between neighborhood SES characteristics and the probability to receive bystander CPR.   Results:  Of the 4,009 OHCA recorded with mappable addresses, 777 (19.4%) received bystander CPR. OHCA victims who received bystander CPR were more likely to be in public locations, with a witnessed cardiac arrest in neighborhoods ranged in low SES, or where median household income was in the highest quartile, and where no high school studies rate and blue collar worker rate were in the lowest quartile (p   Conclusion:  In the city of Paris, OHCA victims were less likely to receive bystander CPR in low SES neighborhoods. These first European data are in agreement with what we have observed from North American and Asian countries.
Peripheral eosinophil count as a biomarker for the management of COPD: not there yet
Authors: Klaus F. Rabe, Bianca Beghé, Leonardo M. Fabbri
Journal: European Respiratory Journal (2017)

Chronic obstructive pulmonary disease (COPD) is associated with acute and chronic pulmonary as well as systemic inflammation [1]. Anti-inflammatory treatments, such as inhaled corticosteroids (ICS) and oral roflumilast, are recommended for COPD patients [2]. These drugs are effective agents for the prevention of COPD exacerbations and improvement of lung function and have various effects on health status, but they are associated with adverse events, the most concerning being pneumonia (ICS) and diarrhoea (roflumilast). Peripheral eosinophils are poorly reproducible; persistent peripheral eosinophilia predicts better outcomes in COPD <http://ow.ly/3hvH30gnxkB>
Discussions about hospice among patients with advanced cancer.
Authors: Lara Traeger, Emily M. Wright, Areej El-Jawahri, Emily R. Gallagher, Joseph Greer, Jennifer S. Temel
Journal: Journal of Clinical Oncology (2017)

53 Background: Timely and effective patient-clinician communication about treatment options at the end of life (EOL) is considered essential to quality care. In this study we examined the timing and nature of first discussions about hospice. We hypothesized that earlier initiation of hospice discussions would be associated with longer hospice length of stay. Methods: We analyzed data from a randomized trial of early palliative care integrated with oncology care versus oncology care alone in patients with newly diagnosed incurable lung or non-colorectal gastrointestinal cancer at the Massachusetts General Hospital (n = 350, enrolled 5/11-7/15). Analysis included patients deceased at 1 year after last enrollment (n = 259). Electronic health records were reviewed to identify first documented hospice discussion with a medical oncology or palliative care clinician. Among hospice enrollees, we tested the association of first hospice discussion with hospice length of stay, adjusting for cancer type and randomized group. We used content analysis to explore the nature of first hospice discussions. Results: Prior to death, 79.9% of patients (54% male; M age = 64 yrs [SD = 11 yrs]) enrolled in hospice. Among hospice enrollees, 8.2% had no documented hospice discussion before enrollment. Range of time from first hospice discussion to hospice enrollment was ≤7 days (40.0%), 8-14 days (12.1%), 15-30 days (13.2%) or &gt; 30 days (34.7%). Greater number of days between first hospice discussion and hospice enrollment was associated with more days on hospice (Beta = .14, SE = .04, p &lt; .001). Almost half of first hospice discussions involved initiation of hospice referral. Discussions that occurred early ( &gt; 30 days before enrollment) were varied, reflecting clinician’s provision of information; discussion of future hospice use; and initiation of dialog about patient/family areas of ambivalence or concern. Conclusions: Earlier initiation of hospice discussions was associated with more subsequent days on hospice and reflected attention to patient/family informational needs, perspectives and concerns about hospice and EOL care. Research is needed to help identify and address factors that facilitate earlier discussions with patients/families about EOL care options.
Quercetin prevents spinal motor neuron degeneration induced by chronic excitotoxic stimulus by a sirtuin 1-dependent mechanism
Authors: Rafael Lazo-Gomez, Ricardo Tapia
Journal: Translational Neurodegeneration (2017)

Excitotoxicity is a mechanism of foremost importance in the selective motor neuron degeneration characteristic of motor neuron disorders. Effective therapeutic strategies are an unmet need for these disorders. Polyphenols, such as quercetin and resveratrol, are plant-derived compounds that activate sirtuins (SIRTs) and have shown promising results in some models of neuronal death, although their effects have been scarcely tested in models of motor neuron degeneration. In this work we investigated the effects of quercetin and resveratrol in an in vivo model of excitotoxic motor neuron death induced by the chronic infusion of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) into the rat spinal cord tissue. Quercetin and resveratrol were co-infused with AMPA and motor behavior and muscle strength were assessed daily for up to ten days. Then, animals were fixed and lumbar spinal cord tissue was analyzed by histological and immunocytological procedures. We found that the chronic infusion of AMPA [1 mM] caused a progressive motor neuron degeneration, accompanied by astrogliosis and microgliosis, and motor deficits and paralysis of the rear limbs. Quercetin infusion ameliorated AMPA-induced paralysis, rescued motor neurons, and prevented both astrogliosis and microgliosis, and these protective effects were prevented by EX527, a very selective SIRT1 inhibitor. In contrast, neither resveratrol nor EX527 alone improved motor behavior deficits or reduced motor neuron degeneration, albeit both reduced gliosis. These results suggest that quercetin exerts its beneficial effects through a SIRT1-mediated mechanism, and thus SIRT1 plays an important role in excitotoxic neurodegeneration and therefore its pharmacological modulation might provide opportunities for therapy in motor neuron disorders.
Disparities in State-Specific Adult Fruit and Vegetable Consumption — United States, 2015
Authors: Seung Hee Lee-Kwan, Latetia V. Moore, Heidi M. Blanck, Diane M. Harris, Deb Galuska
Journal: MMWR Morbidity and Mortality Weekly Report (2017)

The 2015-2020 Dietary Guidelines for Americans recommend that Americans consume more fruits and vegetables as part of an overall dietary pattern to reduce the risk for diet-related chronic diseases such as cardiovascular disease, type 2 diabetes, some cancers, and obesity (1). Adults should consume 1.5-2.0 cup equivalents of fruits and 2.0-3.0 cups of vegetables per day.* Overall, few adults in each state met intake recommendations according to 2013 Behavioral Risk Factor Surveillance System (BRFSS) data; however, sociodemographic characteristics known to be associated with fruit and vegetable consumption were not examined (2). CDC used data from the 2015 BRFSS to update the 2013 report and to estimate the percentage of each state's population meeting intake recommendations by age, sex, race/ethnicity, and income-to-poverty ratio (IPR) for the 50 states and District of Columbia (DC). Overall, 12.2% of adults met fruit recommendations ranging from 7.3% in West Virginia to 15.5% in DC, and 9.3% met vegetable recommendations, ranging from 5.8% in West Virginia to 12.0% in Alaska. Intake was low across all socioeconomic groups. Overall, the prevalence of meeting the fruit intake recommendation was highest among women (15.1%), adults aged 31-50 years (13.8%), and Hispanics (15.7%); the prevalence of meeting the vegetable intake recommendation was highest among women (10.9%), adults aged ≥51 years (10.9%), and persons in the highest income group (11.4%). Evidence-based strategies that address barriers to fruit and vegetable consumption such as cost or limited availability could improve consumption and help prevent diet-related chronic disease.
Predictors of quality of life in non-muscle-invasive bladder cancer survivors.
Authors: Ahrang Jung, Jamie Crandell, Matthew Edward Nielsen, Sophia Kustas Smith, Mary H. Palmer, Ashley Leak Bryant, Deborah Mayer
Journal: Journal of Clinical Oncology (2017)

193 Background: Non-muscle-invasive bladder cancer (NMIBC) survivors face frequent invasive surveillance cystoscopies, repeated treatment, and the highest recurrence rates and medical cost among all cancer survivors for the remainder of their lifespan. Despite the burdens of survivorship for this group, very little is known about the quality of life (QOL) impact of NMIBC diagnosis. We identified factors associated with QOL in NMIBC survivors. Methods: 2000 patients were randomly selected from the 5979 NMIBC population diagnosed between 2010-2014 in North Carolina. These patients received a mailed survey including cancer-specific (EORTC QLQ-C30) and NMIBC-specific (QLQ-NMIBC24) measures of QOL. QOL in this population was described, and hierarchical multiple linear regression was used to determine which patient and disease characteristics are associated with QOL. Results: 376 survivors were included in the analyses (response rate 22%). The mean QOL scores for the following domains include (range 0- 100, higher score is better in all domains but symptoms): global health 73.6±21.7, function 84.8±18.5, symptoms 15.5±17.2, NMIBC-specific sexual function 31.5±27.1 and NMIBC-specific sexual enjoyment 48.1±38.1. Survivors reporting significantly lower global health status were more likely to be male (p &lt; .01), lower income (p = .02), stage Tis at diagnosis (p &lt; .01), and have lower cognitive abilities (p &lt; .01). Lower function (p &lt; .01) and higher symptoms (p = .01) were seen in survivors who were not cured or unsure whether were cured (vs. cured). Lower global health status (p &lt; .01) and higher symptoms (p &lt; .01) were found in survivors who had not received intravesical immunotherapy. Lower social support was associated with lower global health status (p &lt; .01) and lower function (p &lt; .01). A higher number of comorbidities and more cognitive general concerns were associated with poorer QOL in all domains (all p &lt; .01). Conclusions: We identified correlates of QOL in NMIBC survivors. Special attention should be given to those with high risk of lower QOL, including patients with more comorbidities, more cognitive general concerns, or lower social support.