tbuckley/cabot-search huggingface dataset:
Demographic variables and risk factors associated with 30-day readmission following colon cancer diagnosis: Analysis of nationwide inpatient sample data 2009-2013.
Authors: Hardik Satish Chhatrala, Shreya Ghetiya, Yashwant Agrawal, Chintan Shah, Sreenivas Chandana, Hemasri Tokala
Journal: Journal of Clinical Oncology (2016)

e13063 Background: Colon cancer is among the leading causes of cancer and cancer mortality. Colon cancer patients undergo frequent hospitalizations pertaining to imaging, colonoscopy, colorectal surgery, and/or chemoradiation depending upon the stage and type of colon cancer. Much focus has been turned recently on reducing 30-day readmission rates to curb health care costs. This study was done to determine demographic parameters and risk factors associated with 30-day readmission rate after index colon cancer admission stay. Methods: Nationwide Inpatient Sample (NIS) data was used to extract data of patients discharged after diagnosis of colon cancer during index admission for years 2009-2013. Patients were identified by Clinical Classification Software (CCS) code 14, corresponding to ICD 9 codes of 1530-39, 1590, 20910-16, 2303, V1005. NIS represents 20% of all hospital data in the US. Patients readmitted within 30 days were identified and demographic parameters and risk factors associated with high readmission rate identified. Chi-square test was performed to assess for differences between variables. Results: We identified a total of 431,978 hospitalizations for colon cancer during this 5-year period where 16.02% patients were readmitted within 30 days after index hospitalizations. Patients aged 18-44 years (18.6%, p < 0.001), male gender (16.5%, p < 0.01), Medicaid insurances (22.4%, p < 0.001), low median income for zip code (16.9%, p < 0.001) were associated with high 30-day readmission rate. The most common identified causes of readmission were complication of surgical procedure (likely colorectal surgery) (20.3 ± 0.77%, p < 0.001), readmission with colon cancer as primary diagnosis (19.7% ± 1.25%), septicemia (5.6% ± 1.5%), intestinal obstruction without hernia (5.0% ± 1.35%) and secondary malignancies (3.5% ± 0.41%). Conclusions: This national database study identifies the demographic variables and risk factors associated with high 30-day readmission rate for colon cancer. Strategies to reduce morbidity and healthcare cost should be targeted more on these high risk groups and the identified causes with increased readmission rate.
Brain Tumor Imaging
Authors: Kevin M. Brindle, José L. Izquierdo-García, David Y. Lewis, Richard J. Mair, Alan J. Wright
Journal: Journal of Clinical Oncology (2017)

Modern imaging techniques, particularly functional imaging techniques that interrogate some specific aspect of underlying tumor biology, have enormous potential in neuro-oncology for disease detection, grading, and tumor delineation to guide biopsy and resection; monitoring treatment response; and targeting radiotherapy. This brief review considers the role of magnetic resonance imaging and spectroscopy, and positron emission tomography in these areas and discusses the factors that limit translation of new techniques to the clinic, in particular, the cost and difficulties associated with validation in multicenter clinical trials.
Phase II trial of darinaparsin (ZIO-101) in leukemias and lymphomas
Authors: M. Craig, M. Tallman, R. Boccia, M. Gupta, S. Shah, B. Schwartz, J. Buck, I. Lossos
Journal: Cancer Research (2008)

5527  Background: Darinaparsin (ZIO-101; S-dimethylarsino-glutathione), a novel organic arsenic, has a multifunctional mechanism of action that is mediated by disrupted mitochondrial function, increased reactive oxygen species (ROS) production, modified signal transduction, and antiangiogenesis. Darinaparsin is active against diverse cancers in vitro and in animal models of leukemia and lymphoma.  Methods: Phase II trial in patients with advanced hematological malignancies (ongoing). Patients receive darinaparsin intravenously (IV) for 5 consecutive days every 28 days until disease progression or significant toxicity occurs.  Preliminary results: A total of 18 patients (13 males, 5 females) (13 Caucasian, 2 Asian, 2 black, 1 Hispanic), with ECOG performance scores
Attention problems as a risk factor for concussion in youth ice-hockey players
Authors: Tommy Gerschman, Kathryn Schneider, Keith Yeates, Brian L Brooks, Courtney Kipps, Carolyn Emery
Journal: British Journal of Sports Medicine (2017)

Objective To examine attention problems in youth ice-hockey players as a risk factor for concussion. Design Secondary analysis of two prospective cohort studies. Setting Ice-rinks and Sport Medicine Centres in two Canadian cities over three ice-hockey seasons (2011/12, 2012/13, 2014/15). Assessment of risk factors Self-report of formal diagnosis of attention or learning disorders were collected on previously validated preseason baseline questionnaires by all participating players. Parents and players completed the Behaviour Assessment System for Children (BASC-2), which includes inattention and hyperactivity scales. Participants 2,364 Canadian ice-hockey players (11–17 years old, 87% male). Outcome measures A previously validated prospective injury surveillance system was used. All suspected concussions were referred to the study physician for confirmation of diagnosis. Concussion risk ratios (RR) were estimated, including stratification by known risk factors. Results One-hundred ninety-two of 2,215 players (9%) self-reported attention and/or learning disorders at baseline. Overall, 256 players (11%) sustained one or more concussions during a season. Players identified as “at-risk” for attention-deficit hyperactivity disorder (ADHD), based on BASC-2 T-scores (inattention and/or hyperactivity scale) greater than 60, had a greater risk of concussion during the season based on child report [RR=1.51 (95% CI 1.13–2.04)] and parent report [2.97 (95% CI 1.65–5.34)]. In players with no history of previous concussion, the RR based on child report was 1.88 (95% CI 1.22–2.90) and based on parent report was 5.03 (95% CI 2.45–10.29). Conclusions Ice-hockey players identified as “at-risk” for ADHD on the basis of baseline BASC-2 scores are at a greater risk of concussion. Competing interests None.
Rapid priming of human monocytes by human hematopoietic growth factors: granulocyte-macrophage colony-stimulating factor (CSF), macrophage-CSF, and interleukin-3 selectively enhance superoxide release triggered by receptor-mediated agonists
Authors: A Yuo, S Kitagawa, K Motoyoshi, E Azuma, M Saito, F Takaku
Journal: Blood (1992)
Elucidating Mechanisms of Sensitivity and Resistance to EGFR Tyrosine Kinase Inhibitors in Lung Cancer
Authors: William Pao
Journal: Clinical Cancer Research (2007)

PL08-02    Elucidating Mechanisms of Sensitivity and Resistance to EGFR Tyrosine Kinase Inhibitors in Lung Cancer  William Pao, MD, PhD  Human Oncology and Pathogenesis Program, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, Box 125, New York, NY 10065, USA   Abstract  The epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), gefitinib (Iressa) and erlotinib (Tarceva), induce dramatic responses in certain patients with non-small cell lung cancer (NSCLC). As such, the drugs provide an unexpected tool to dissect clinically relevant molecular subsets of NSCLC. For example, using mutational profiling of tumor DNA from patients with known clinical outcomes to these drugs, we and others have demonstrated that somatic mutations in the tyrosine kinase domain of  EGFR  are associated with increased sensitivity to gefitinib and erlotinib, while mutations in  KRAS,  which encodes a GTPase downstream of EGFR, are associated with primary resistance.  EGFR  mutations are more commonly found in tumors from patients with a minimal cigarette smoking history, while  KRAS  mutations are more frequent in those with significant direct tobacco exposure. Thus, these two mutations define distinct populations of NSCLC patients with different natural histories and responses to targeted therapy.  Acquired resistance to gefitinib and erlotinib is also a major clinical problem. Nearly all patients who initially respond to treatment eventually develop progressive disease. We and others have found that second site mutations in the EGFR kinase domain are found in about half of patients with acquired resistance to these drugs. The most common (>90%) second-site mutation involves a CaT change at nucleotide 2369 in exon 20, which results in substitution of methionine for threonine at position 790 (T790M). This mutation can rarely be found before treatment and is linked to genetic susceptibility to lung cancer. When compared to “acquired resistance” mutations to kinase inhibitors in others diseases, our data suggest that the type and nature of kinase inhibitor resistance mutations may be influenced by both anatomical site and mode of binding to the kinase target.  We are now using a variety of molecular and biological approaches to define further mechanisms of sensitivity/resistance to gefitinib and erlotinib and to identify additional molecular subsets of lung cancer that have relevance in the clinic. For example, to determine other potential mechanisms of resistance, we compared genomic profiles of  EGFR  mutant tumors from untreated patients with those from patients with acquired resistance and found that  MET  amplification contributes to progressive disease. Others have reported similar findings using a different approach. These data suggest that MET inhibitors could play an important role in the treatment of some patients who develop acquired resistance to first-line EGFR inhibitors.
Pharmacodynamic Profile of a Recombinant ADAMTS13 (BAX930) in Hereditary Thrombotic Thrombocytopenic Purpura (Upshaw-Schulman Syndrome (USS))
Authors: Marie Scully, Paul Knoebl, Karim Kentouche, Lawrence Rice, Jerzy Windyga, Reinhard Schneppenheim, Johanna A Kremer Hovinga, Michiko Kajiwara, Caterina Maggiore, Jennifer Doralt, Leah Martell, Bruce M. Ewenstein
Journal: Blood (2016)
Therapeutic Targeting of the Pyruvate Dehydrogenase Complex/Pyruvate Dehydrogenase Kinase (PDC/PDK) Axis in Cancer
Authors: Peter W Stacpoole
Journal: JNCI Journal of the National Cancer Institute (2017)

The mitochondrial pyruvate dehydrogenase complex (PDC) irreversibly decarboxylates pyruvate to acetyl coenzyme A, thereby linking glycolysis to the tricarboxylic acid cycle and defining a critical step in cellular bioenergetics. Inhibition of PDC activity by pyruvate dehydrogenase kinase (PDK)–mediated phosphorylation has been associated with the pathobiology of many disorders of metabolic integration, including cancer. Consequently, the PDC/PDK axis has long been a therapeutic target. The most common underlying mechanism accounting for PDC inhibition in these conditions is post-transcriptional upregulation of one or more PDK isoforms, leading to phosphorylation of the E1α subunit of PDC. Such perturbations of the PDC/PDK axis induce a “glycolytic shift,” whereby affected cells favor adenosine triphosphate production by glycolysis over mitochondrial oxidative phosphorylation and cellular proliferation over cellular quiescence. Dichloroacetate is the prototypic xenobiotic inhibitor of PDK, thereby maintaining PDC in its unphosphorylated, catalytically active form. However, recent interest in the therapeutic targeting of the PDC/PDK axis for the treatment of cancer has yielded a new generation of small molecule PDK inhibitors. Ongoing investigations of the central role of PDC in cellular energy metabolism and its regulation by pharmacological effectors of PDKs promise to open multiple exciting vistas into the biochemical understanding and treatment of cancer and other diseases.
Urban green and grey space in relation to respiratory health in children
Authors: Christina Tischer, Mireia Gascon, Ana Fernández-Somoano, Adonina Tardón, Aitana Lertxundi Materola, Jesus Ibarluzea, Amparo Ferrero, Marisa Estarlich, Marta Cirach, Martine Vrijheid, Elaine Fuertes, Albert Dalmau-Bueno, Mark J. Nieuwenhuijsen, Josep M. Antó, Jordi Sunyer, Payam Dadvand
Journal: European Respiratory Journal (2017)

We assessed the effect of three different indices of urban built environment on allergic and respiratory conditions.This study involved 2472 children participating in the ongoing INMA birth cohort located in two bio-geographic regions (Euro-Siberian and Mediterranean) in Spain. Residential surrounding built environment was characterised as 1) residential surrounding greenness based on satellite-derived normalised difference vegetation index (NDVI), 2) residential proximity to green spaces and 3) residential surrounding greyness based on urban land use patterns. Information on wheezing, bronchitis, asthma and allergic rhinitis up to age 4 years was obtained from parent-completed questionnaires. Logistic regression and generalised estimating equation modelling were performed.Among children from the Euro-Siberian region, higher residential surrounding greenness and higher proximity to green spaces were negatively associated with wheezing. In the Mediterranean region, higher residential proximity to green spaces was associated with a reduced risk for bronchitis. A higher amount of residential surrounding greyness was found to increase the risk for bronchitis in this region.Associations between indices of urban residential greenness and greyness with respiratory diseases differ by region. The pathways underlying these associations require further exploration.
Applying Precision Medicine to Trial Design Using Physiology. Extracorporeal CO<sub>2</sub> Removal for Acute Respiratory Distress Syndrome
Authors: Ewan C. Goligher, Marcelo B. P. Amato, Arthur S. Slutsky
Journal: American Journal of Respiratory and Critical Care Medicine (2017)

In clinical trials of therapies for acute respiratory distress syndrome (ARDS), the average treatment effect in the study population may be attenuated because individual patient responses vary widely. This inflates sample size requirements and increases the cost and difficulty of conducting successful clinical trials. One solution is to enrich the study population with patients most likely to benefit, based on predicted patient response to treatment (predictive enrichment). In this perspective, we apply the precision medicine paradigm to the emerging use of extracorporeal CO2 removal (ECCO2R) for ultraprotective ventilation in ARDS. ECCO2R enables reductions in tidal volume and driving pressure, key determinants of ventilator-induced lung injury. Using basic physiological concepts, we demonstrate that dead space and static compliance determine the effect of ECCO2R on driving pressure and mechanical power. This framework might enable prediction of individual treatment responses to ECCO2R. Enriching clinical trials by selectively enrolling patients with a significant predicted treatment response can increase treatment effect size and statistical power more efficiently than conventional enrichment strategies that restrict enrollment according to the baseline risk of death. To support this claim, we simulated the predicted effect of ECCO2R on driving pressure and mortality in a preexisting cohort of patients with ARDS. Our computations suggest that restricting enrollment to patients in whom ECCO2R allows driving pressure to be decreased by 5 cm H2O or more can reduce sample size requirement by more than 50% without increasing the total number of patients to be screened. We discuss potential implications for trial design based on this framework.
A phase II clinical trial platform utilizing total neoadjuvant therapy (TNT) in rectal cancer: Nrg-GI002.
Authors: Thomas J. George, Greg Yothers, Theodore S. Hong, Marcia McGory Russell, Patricia A. Ganz, Y. Nancy You, William Parker, Samuel A. Jacobs, Katherine L. Pogue-Geile, Norman Wolmark, Carmen Joseph Allegra
Journal: Journal of Clinical Oncology (2016)

TPS3638 Background: Improvements in outcomes for locally advanced rectal cancer (LARC) have plateaued due to an inability to consistently deliver adjuvant therapy and thus far ineffective novel therapies. Systematic testing of new chemotherapy and radiation sensitizers are needed to advance treatment outcomes. This randomized phase II modular clinical trial platform utilizes Total Neoadjuvant Therapy (TNT) with parallel experimental arms in LARC. The experimental arms are not intended for direct comparison, but to test a variety of sensitizers or hypotheses in a consistent and relatively homogenous high-risk patient (pt) population with correlative biomarkers. Success of any given experimental arm will be determined by achievement of pathologic endpoints compared to a control arm. Methods: This NCTN multi-arm randomized phase II trial serves as a modular platform to assess novel sensitizers to neoadjuvant chemotherapy and/or chemoradiotherapy (chemoRT) in LARC. Eligibility includes LARC as defined by any ONE of the following criteria: distal location (cT3-4 ≤ 5cm from the anal verge, any N); bulky (any cT4 or tumor within 3mm of the mesorectal fascia); high risk for metastatic disease (cN2); or not a candidate for sphincter-sparing surgical resection. After randomization, all pts receive neoadjuvant FOLFOX x 4mo → chemoRT (capecitabine with 50.4Gy) → surgical resection 8-12 wks later. Based on promising phase I results, the first experimental arm will assess the activity of veliparib added to standard chemoRT (capecitabine + RT). Primary endpoint is to demonstrate an improvement in Neoadjuvant Rectal Cancer (NAR) score for the experimental arm vs control representing a 20% relative risk reduction in DFS HR and 3-4% absolute OS improvement. Secondary endpoints include comparisons of OS, DFS, toxicity, pCR, cCR, therapy completion, negative surgical margins, sphincter preservation, sphincter function including quality of life, and exploratory assessments of molecular predictors of response and distant failure. Target accrual is 79 evaluable pts per arm with additional arms added through protocol amendments. NCT # pending. Support: U10 CA-180868, -180822, UG-189867; AbbVie.
Risk Adjusted Management of Newly Diagnosed High and Intermediate FLIPI Follicular Lymphoma Using (90)Y Ibritumomab Tiuxetan
Authors: Neil L Berinstein, Nancy M Pennell, Rashmi Weerasinghe, Matthew C. Cheung, Eugenia Piliotis, Kevin R Imrie, Mary-Anne Cussen, Rena Buckstein, Zeina Ghorab, Ellen Miles, Marciano D. Reis
Journal: Blood (2016)
Different cell activities in breast cancer based on different estrogen receptor-alpha(+)/estrogen receptor-alpha(-) ratios.
Authors: Yanchu Li, Zhang Hengli, Gou Qiheng, Zhang Jiahui, Ping Li
Journal: Journal of Clinical Oncology (2016)

e12004 Background: Estrogen receptor-alpha (ERα) is implicated in breast cancer progression. Although tamoxifen and aromatase inhibitors have been widely used to treat ERα-positive breast cancer, the least favorable ERα(+)/ERα(-) expression ratio in the tumor microenvironment and its influence on tumor activity remain poorly understood. We examined different ERα(+)/ERα(-) ratios in an MDA-MB-231 model to identify the least favorable ERα(+)/ERα(-) ratio. Methods: ERα stable transfectants were created in the MDA-MB-231 ER(-) cell line, and the MCF-7 ER(+) cell line was used as a control. Transfected MDA-MB-231 ER(+) and wild-type MDA-MB-231 ER(-) cells were mixed and co-cultured at 100%, 70%, 40%, 20%, and 0% ratios. Migration and invasion abilities of the different cell ratios were evaluated in vitro. Type 2 macrophage transformation; BRCA1 and Her2 expression; and VEGF and TNF-α expression in vivo were measured, and bone and lung metastasis were examined in vivo. Results: The results of transwellassays with fluorescence staining were 249±6, 404±28, 430±25, 401±25, and 361±20 cells for the different mixing ratios and 350±10 cells for the control, respectively (high to low), and wound healing tests with quantitative analysis showed the highest migration rate (84%±5) was for the 40% ratio after 48 h of co-culture. The flow cytometry results for the F4/80(+)/Ly6c(+)proportions were 5.0%±0.56, 7.7%±0.5, 7.2%±0.49, 6.2%±0.57 and 4.9%±0.69 for the different ratios and 4.2%±0.46 for the control, respectively. Immunohistochemical staining and western blotting indicated that 70% ratio had the highest VEGR and TNF-α and BRCA1 and Her2 expression levels in vivo. Lung and bone metastasis were observed in the 70% group. Conclusions: ERα(+)/ERα(-) ratios of 40% in vitro and 70% in vivo serve as critical indicators of cell activity and cytokine expression. Our results suggest that breast cancer cell activity does not exhibit a linear relationship with ERα-positive expression, which indicates that ER status requires multiple checks during tamoxifen or aromatase inhibitor treatment. These results indicate a new therapeutic strategy for preventing ER-positive breast cancer.
The common approach to the treatment of women with triple negative breast cancer in Saint-Petersburg. Russia.
Authors: Alla Sergeevua Lisyanskaya, Alexey Manikhas, Roman Babeshkin, Leonid Li, Ivan Grinev, Alexander Shemerovskiy, Vitaly Skvortsov, Armen Oganesyn, Georgy M. Manikhas
Journal: Journal of Clinical Oncology (2016)

e12579 Background: Triple negative breast cancer (TNBC) is extremely aggressive form of malignant breast tumors with high levels of metastasis, frequent occurrence of relapse and low survival compared with other subtypes of breast cancer. Methods: 1018 patients are selected for the investigation (age 21 to 88, the average age is 52 years) with histologically verified invasive breast cancer 1-3 A extent with triple-negative phenotype (TNBC). TNBC elected patients were divided into 3 groups: Group A – have been given neoadjuvant systematic therapy – 201 patients (in 19.7% cases). Group B – have been given adjuvant treatment – 729 (in 71.6% cases). Group C – have not been given any treatment apart from surgery due to some reasons (health or patients’ refusal) – 88 (in 8.6% cases). All the patients had been treated in City Clinical Oncology Dispensary since 2005 until 2011. They had different types of chemotherapy: CMF, FAC/FEC, taxane comprising variations (T, TC, AT, TAC), as a surgical treatment either radical mastectomy (Madden) or the radical sectoral breast resection has been applied. For all chosen groups disease-free survival is evaluated (DFS) with the investigation of minimum of 36 months. The analysis is performed using the international static program SPSS 20.0. Discrepancy was taken in account if p < 0.05. Results: Recurrence rate (local, regional, farther) of the disease is definitely higher in group C in comparison to to group A (35.8% vs 11.9%, p < 0.05); coincident data is obtained by analyzing the mortality rate from all causes (27.2% vs 8.5%, p < 0.05) and mortality rate from cancer (24.9% vs 6.8%, p < 0.05). For group A the DFS rates is significantly higher than for the patients have not been taken the neoadjuvant therapy (90.8% vs 74.9%, p < 0.05). Conclusions: complex triple-negative breast cancer medicine therapy has to be started with neoadjuvant chemotherapy followed by the surgical and adjuvant treatment. This scheme has an incredibly important prognostic meaning dealing with TNBC and provides much better indexes in survival overall as well as in the disease-free survival.
Le score de Blatchford n'aide pas à la décision de réalisation en urgence de l'endoscopie au cours de l'hémorragie digestive haute de l'adulte
Authors: V Humbert-Sebbagh, A Attar, P Le Toumelin, I Le Groupe des Endoscopistes de Garde, À l'ap-Hp, Y Bouhnik
Journal: Endoscopy (2005)

Blatchford et al. A établi un score de risque clinique et biologique [urémie, hémoglobine, pression artérielle systolique, pouls, méléna, syncope, maladie du foie et insuffisance cardiaque] coté de 0 à 23 afin d'aider à la décision de réalisation en urgence de l'endoscopie au cours de l'hémorragie digestive haute de l'adulte. Nous avons réalisé un essai prospectif de validation externe de ce score chez des patients atteints d'hémorragie digestive haute pour lesquels la gastroscopie était demandée en urgence pendant les heures de garde.