tbuckley/cabot-search huggingface dataset:
Examination of utility in patients of unresectable or recurrent gastric cancer treated with paclitaxel or nab-paclitaxel or paclitaxel+ ramucirumab in our hospital
Authors: T. Kii, M. Gotoh, T. Terazawa, T. Yamaguchi, K. Asaishi, M. Aoki, T. Ikegami, K. Higuchi
Journal: Annals of Oncology (2017)
PAX3-FOXO1: Zooming in on an “undruggable” target
Authors: Marco Wachtel, Beat W. Schäfer
Journal: Seminars in Cancer Biology (2017)

Driver oncogenes are prime targets for therapy in tumors many of which, including leukemias and sarcomas, express recurrent fusion transcription factors. One specific example for such a cancer type is alveolar rhabdomyosarcoma, which is associated in the majority of cases with the fusion protein PAX3-FOXO1. Since fusion transcription factors are challenging targets for development of small molecule inhibitors, indirect inhibitory strategies for this type of oncogenes represent a more promising approach. One can envision strategies at different molecular levels including upstream modifiers and activators, epigenetic and transcriptional co-regulators, and downstream effector targets. In this review, we will discuss the current knowledge regarding potential therapeutic targets that might contribute to indirect interference with PAX3-FOXO1 activity in alveolar rhabdomyosarcoma at the different molecular levels and extrapolate these findings to fusion transcription factors in general.
Mitochondrial DNA content in peripheral blood as a biomarker for cancer-related fatigue in early-stage breast cancer patients: A prospective cohort study.
Authors: Jung-Woo Chae, Peh Siang Chua, Terence NG, Hui Ling Angie Yeo, Maung Shwe, Yan Xiang Gan, Sreemanee Raaj Dorajoo, Koon Mian Foo, Kiley Wei Jen Loh, Si-Lin Koo, Wen Yee Chay, Tira Jing Ying Tan, Sok Yuen Beh, Hsuen Elaine Lim, Guek Eng Lee, Rebecca Alexandra Dent, Yoon Sim Yap, Raymond C.H. Ng, Han Kiat Ho, Alexandre Chan
Journal: Journal of Clinical Oncology (2017)

10018 Background: Cancer-related fatigue (CRF) is reported to be associated with mitochondrial dysfunction. Hence, mitochondrial DNA (mtDNA) content, a biomarker of mitochondrial dysfunction, is hypothesized to correlate with the onset of CRF. This study aimed to evaluate the association between peripheral blood mtDNA content and CRF in patients receiving chemotherapy. Methods: This was a prospective cohort study. Early-stage breast cancer patients (Stages I to III) receiving anthracycline or taxane-based chemotherapy were recruited. CRF was assessed using the validated Multidimensional Fatigue Symptom Inventory-Short Form (MFSI-SF) at two time points: baseline (T1; prior to treatment) and 6 weeks after initiation of treatment (T2). Worsening of CRF was defined as ≥10% increase in the overall MFSI-SF score at T2. Peripheral blood mtDNA content was measured at both time points using real-time quantitative polymerase chain reaction. Multiple logistic regression was utilized to evaluate the association between mtDNA reduction and worsening of CRF, adjusting for age, anxiety, insomnia and other clinically important covariates. Results: A total of 91 patients [mean age (±SD): 51.3 (9.2) years; 81.3% Chinese; 63.3% receiving anthracycline-based chemotherapy] were recruited. Proportions of patients with worsening of CRF increased from the lower to the upper quartiles of mtDNA reduction (26.1%, 30.4%, 52.2%, and 59.1% in quartiles 1, 2, 3, and 4, respectively, P = 0.010 for trend). Reduction of mtDNA content was significantly greater among those with worsening of CRF compared to those without CRF [mean reduction (±SD): 16.3 (23.5) vs 6.0 (17.3), P = 0.018]. After adjusting for covariates, every 1-unit reduction of the mtDNA content was associated with a 4% increase risk for worsening of CRF (95% CI, 1%-8%; P = 0.016). Conclusions: This is the first study to show that reduction of mtDNA content in peripheral blood is associated with onset of CRF in patients receiving chemotherapy. Further validation studies are required to confirm the findings.
Review: In age-related macular degeneration, antioxidant multivitamins and zinc supplements each decrease progression
Authors: Lorraine Macdonald
Journal: Annals of Internal Medicine (2017)

Source Citation Evans JR, Lawrenson JG. Antioxidant vitamin and mineral supplements for slowing the progression of age-related macular degeneration. Cochrane Database Syst Rev. 2017;7:CD000254. 28756618
Febrile neutropenia risk with adjuvant TC (docetaxel and cyclophosphamide) regimen: Experience of Brazilian cancer centers.
Authors: Joao Paulo Velloso Medrado Santos, Debora De Melo Gagliato, Rachel Jorge Dino Cossetti, Rodrigo Darouche Gimenez, Max S. Mano
Journal: Journal of Clinical Oncology (2014)

e12002 Background: In patients diagnosed with Breast Cancer (BC), adjuvant chemotherapy is an important treatment strategy toreduce risk of breast and systemic recurrence, as well as cancer death. The combination of Docetaxel and Cyclophosphamide (TC) is a well-recognized effective regimen. Nonetheless, a considerable high rate of febrile neutropenia (FN) may be associated with this regimen. We sought to investigate hematologic toxicity associated with adjuvant TC in a non-selected cohort of BC patients. Methods: We reviewed the electronic medical records of patients who presented to the Oncology Center from Hospital Sirio-Libanes (HSL) and Instituto do Cancer do Estado de Sao Paulo (ICESP) after definitive breast surgery to initiate adjuvant chemotherapy with TC. Results: 95 patients with early BC were included in our analysis. Median age was 55.5 years. All patients had a good performance status (Ecog 0 or 1) and the great majority of them had no comorbidities. Four chemotherapy cycles were given for most patients (80%). Data on G-CSF administration was available in 85 patients from our cohort. G-CSF was used as primary prophylaxis in 31 patients and in 13 patients as secondary prophylaxis, following a prior diagnosis of febrile neutropenia. Overall, fifteen women (15.8%) had a documented FN episode. Among women who received G-CSF as primary prophylaxis, the rate of FN was 6.45% (2 patients). In contrast, among patients who did not receive primary prophylaxis with G-CSF, the FN rate was considerably higher, namely 24.07% (13 patients). Patients who received primary prophylaxis with G-CSF had a statistically significant lower risk of experiencing a FN episode (p 0.049). Conclusions: Febrile Neutropenia rate in this group of non-selected BC patients was higher than previous reported on randomized controlled trials that evaluated adjuvant TC regimen in the same dosing and schedule as used in our cohort. Primary prophylaxis with G-CSF was associated with a statistically significant lower risk of FN and should be used in the management of patients who receive this chemotherapy combination.
Abstract 14072: Incidence of Stent Thrombosis and Its Predictors After Endovascular Therapy for Femoropopliteal Artery Disease
Authors: Takuya Tsujimura, Osamu Iida, Masashi Fujita, Masaharu Masuda, Shin Okamoto, Kiyonoori Nanto, Takashi Kanda, Tatsuya Shiraki, Akihiro Sunaga, Shota Okuno, Yasuhiro Matsuda, Koji Yanaka, Takuya Ohashi, Masaaki Uematsu
Journal: Circulation (2015)

Background: Stent thrombosis (ST) in the coronary artery has been associated with a high mortality rate (45%). Despite its broad use, incidence of ST and its impact on clinical outcome following endovascular therapy (EVT) for femoropopliteal (FP) lesions have not been systematically studied. Methods: Five hundred and fifty-nine consecutive patients (74±9 years; 33% female; 47% with critical limb ischemia; 31% TASC C/D) who underwent stent implantation (81% bare metal and 19% drug-eluting stents) in FP lesions (length, 157±100 mm) were retrospectively studied. ST was diagnosed when the following criteria were met: 1) initial procedural success; 2) rapid symptom occurrence; 3) thrombus present at procedure; and 4) lesion resolved with &lt;50% diameter narrowing by thrombolysis. We evaluated the incidence of ST and its impact on major adverse limb event (MALE)-free survival by Kaplan-Meier analysis and by Cox proportional hazard model. Results: Rate of ST linearly increased during the follow-up and reached 1.6% (7/559) at 36 months following stent implantation. MALE-free survival rate was 74.6% at 36 months after stent implantation. The independent predictors were age (HR), body mass index (HR), CLI (HR), hemodialysis (HR), and chronic heart failure (HR), while ST (0.99; [0.14-7.33] was not significantly associated with MALE-free survival. Conclusion: ST, which occurred in 1.6% at 36 months after stent implantation, was not an independent predictor of MALE-free survival in patients with PAD in FP lesions.
Using electronic patient reported outcomes to identify gaps in quality of care in radiation oncology.
Authors: Celine Denise Marquez, Steve E. Braunstein, Olivier Morin, Shannon E. Fogh
Journal: Journal of Clinical Oncology (2017)

94 Background: Improving quality of care involves identifying patient health needs and designing systems to meet those needs reliably. Within Radiation Oncology, patient health needs encompass measurable, physical quantities such as a reduction in tumor size, as well as subjective needs, as in freedom from pain. Patient reported outcomes (PRO) have the potential to identify subjective health needs and to guide treatment towards symptoms patients find most bothersome, thereby improving quality of care. Here we report the unmet health needs revealed by systematic electronic PRO data collection in a Radiation Oncology department. Methods: 50 consecutively treated patients for a variety of malignant and nonmalignant, primary and metastatic disease were surveyed within the CNS subdivision of a single Radiation Oncology department using electronic EORTC QLQ C30 or PRO-CTCAE CNS forms displayed on a touch screen tablet. Patients were then followed with PRO surveys at two additional time points, 1-2 weeks post radiotherapy treatment and again at one month. Results: Of 27 planned PRO CTCAE surveys of 9 patients, 22 (81%) were completed and available for evaluation. 6/9 (67%) of patients taking the PRO CTCAE reported “severe” or “very severe” side effects. The most commonly reported “severe” or “very severe” symptoms were fatigue (6/9, 67%), insomnia (3/9, 33%), anxiety (2/9, 22%), and sad/unhappy feelings (2/9, 22%). Of 123 planned EORTC QLQ C30 surveys of 41 patients, 109 (89%) were completed and accessible for evaluation. 38/41 (93%) of patients taking EORTC QLQ C30 reported side effects impacting their lives “quite a bit” or “very much”. The most common symptoms impacting patients “quite a bit” and/or “very much” were fatigue (25/41, 61%), pain (17/41, 41%), insomnia (15/41, 37%), and worry (14/41, 34%). Conclusions: Gaps that may exist between the quality of care we wish to provide and the care patients experience may be recognized and addressed by incorporating PROs into our standard clinical practice. Integrating electronic PROs into our clinical systems will help us to more reliably identify unmet patient health needs, personalize care, and respond to side effects and symptoms that are of the greatest concern to patients.
Prevalence of persistent blood eosinophilia: relation to outcomes in patients with COPD
Authors: Ciro Casanova, Bartolome R. Celli, Juan P. de-Torres, Cristina Martínez-Gonzalez, Borja G. Cosio, Victor Pinto-Plata, Pilar de Lucas-Ramos, Miguel Divo, Antonia Fuster, Germán Peces-Barba, Myriam Calle-Rubio, Ingrid Solanes, Ramón Aguero, Nuria Feu-Collado, Inmaculada Alfageme, Alfredo De Diego, Amparo Romero, Eva Balcells, Antonia Llunell, Juan B. Galdiz, Margarita Marin, Amalia Moreno, Carlos Cabrera, Rafael Golpe, Celia Lacarcel, Joan B. Soriano, José Luis López-Campos, Juan J. Soler-Cataluña, José M. Marin
Journal: European Respiratory Journal (2017)

The impact of blood eosinophilia in chronic obstructive pulmonary disease (COPD) remains controversial. To evaluate the prevalence and stability of a high level of blood eosinophils (≥300 cells·μL –1 ) and its relationship to outcomes, we determined blood eosinophils at baseline and over 2 years in 424 COPD patients (forced expiratory volume in 1 s (FEV 1 ) 60% predicted) and 67 smokers without COPD from the CHAIN cohort, and in 308 COPD patients (FEV 1 60% predicted) in the BODE cohort. We related eosinophil levels to exacerbations and survival using Cox hazard analysis. In COPD patients, 15.8% in the CHAIN cohort and 12.3% in the BODE cohort had persistently elevated blood eosinophils at all three visits. A significant proportion (43.8%) of patients had counts that oscillated above and below the cut-off points, while the rest had persistent eosinophil levels &lt;300 cells·μL –1 . A similar eosinophil blood pattern was observed in controls. Exacerbation rates did not differ in patients with and without eosinophilia. All-cause mortality was lower in patients with high eosinophils compared with those with values &lt;300 cells·μL –1 (15.8% versus 33.7%; p=0.026). In patients with COPD, blood eosinophils ≥300 cells·μL –1 persisting over 2 years was not a risk factor for COPD exacerbations. High eosinophil count was associated with better survival.
Engaging oncologists toward integrating a shared mental model for palliative oncology within a large academic oncology practice.
Authors: Anne Margaret Walling, Christopher Pietras, Kauser Ahmed, Anne Coscarelli, Sara A. Hurvitz, Wendy Simon, Peter Phung, Meghan Nechrebecki, Sarah F. DAmbruoso, Neil Wenger, Jennie Kung, Jonathan Wade Goldman, Lee S. Rosen, Drakaki Alexandra, Parvin F. Peddi, Deborah J. Wong, John A. Glaspy
Journal: Journal of Clinical Oncology (2017)

105 Background: We aimed to engage oncologists to disseminate a successful pilot-tested shared mental model (SMM) for the integration of early advance care planning (ACP) and identification of palliative care (PC) needs across a health system’s oncologic practice. Methods: Our Oncology Communication Collaborative Team (OCCT) had oncology leadership support and included a multidisciplinary team representing leaders in oncology, ACP, PC, psycho-social oncology and quality. To communicate the SMM developed by our team, the OCCT developed an interactive Saturday session (1-hr didactic, 3-hr small group role-play) that focused on early ACP and the cognitive and emotional aspects of communication. Before and after the training, we asked participants to rate their ability to communicate with patients as well as their readiness, self-efficacy, and need for help to improve communication regarding prognosis, ACP, end of life care and symptom management using a previously validated survey. We computed means and compared matched pairs of pre and post surveys using a paired t-test. We also surveyed participants about whether they would recommend the course to others and planned changes to practice. Results: All but one oncologist (52/53), 3/4 invited fellows, and 12/14 oncology nurse practitioners participated and 90% of attendees completed pre and post surveys. Participants rated their communication ability higher (6.7 v. 7.6, p &lt; 0.01) on a 10-point scale after the training. Readiness to improve communication in this domain (9.1 v. 9.2, p = 0.35) was similar before and after the training. Self-efficacy (1.5 v. 1.5, p = 0.70) and needing help to improve (1.6 v. 1.7, p = 0.37) were rated highly (1 = A lot and 4 = Not at all) but did not change with training. All but one participant reported they would recommend the course to others and free text responses about changes they planned to make to their practice based on the training included: having earlier ACP discussions, focusing on patient goals/priorities and asking open-ended questions. Conclusions: Conducting a training to disseminate a SMM of oncology and PC is feasible, valuable, and can be the first step for partnered continuous quality improvement.
The Hospital Readmissions Reduction Program—Targeting Weaknesses and Finding the Readmission Floor
Authors: Ryan J. Ellis, Ryan P. Merkow, Karl Y. Bilimoria
Journal: JAMA Surgery (2017)

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Nimotuzumab post marketing surveillance study: A Sri Lanka experience
Authors: M. Perera, K A S J Balawardana, T. Skandharajah, L. Obeysekere, A.J. Hilmi, N. Yoganathan, S. Kandegedera, U.G. Sarawanamutthu, M. Netthikumar, K. Indranatha, D. Pawar
Journal: Annals of Oncology (2017)
P3.02b-088 TKI as First Line Treatment in Advanced Non-Small-Cell Lung Cancer with EGFR Mutations
Authors: Inês Guerreiro, Ana Vitor Silva, Ana Rodrigues, Cristina Oliveira, Inés Pousa, Júlio Oliveira, Isabel Azevedo, Marta Soares
Journal: Journal of Thoracic Oncology (2017)
Vascular peroxidase 1 mediates hypoxia-induced pulmonary artery smooth muscle cell proliferation, apoptosis resistance and migration
Authors: Baiyang You, Yanbo Liu, Jia Chen, Xiao Huang, Huihui Peng, Zhaoya Liu, Yixin Tang, Kai Zhang, Qian Xu, Xiaohui Li, Guangjie Cheng, Ruizheng Shi, Guogang Zhang
Journal: Cardiovascular Research (2017)

Reactive oxygen species (ROS) play essential roles in the pulmonary vascular remodelling associated with hypoxia-induced pulmonary hypertension (PH). Vascular peroxidase 1 (VPO1) is a newly identified haeme-containing peroxidase that accelerates oxidative stress development in the vasculature. This study aimed to determine the potential role of VPO1 in hypoxia-induced PH-related vascular remodelling.The vascular morphology and VPO1 expression were assessed in the pulmonary arteries of Sprague-Dawley (SD) rats. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 4 (NOX4) and VPO1 expression and HOCl production were significantly increased in hypoxic rats, which also exhibited obvious vascular remodelling. Furthermore, a hypoxia-induced PH model was generated by exposing primary rat pulmonary artery smooth muscle cells (PASMCs) to hypoxic conditions (3% O2, 48 h), which significantly increased the expression of NOX4 and VPO1 and the production of HOCl. These hypoxic changes were accompanied by enhanced proliferation, apoptosis resistance, and migration. In PASMCs, hypoxia-induced changes, including effects on the expression of cell cycle regulators (cyclin B1 and cyclin D1), apoptosis-related proteins (bax, bcl-2, and cleaved caspase-3), migration promoters (matrix metalloproteinases 2 and 9), and NF-κB expression, as well as the production of HOCl, were all inhibited by silencing VPO1 with small interfering RNAs. Moreover, treatment with HOCl under hypoxic conditions upregulated NF-κB expression and enhanced proliferation, apoptosis resistance, and migration in PASMCs, whereas BAY 11-7082 (an inhibitor of NF-κB) significantly inhibited these effects.Collectively, these results demonstrate that VPO1 promotes hypoxia-induced proliferation, apoptosis resistance, and migration in PASMCs via the NOX4/VPO1/HOCl/NF-κB signalling pathway.
Myofilament Calcium-Buffering Dependent Action Potential Triangulation in Human-Induced Pluripotent Stem Cell Model of Hypertrophic Cardiomyopathy
Authors: Lili Wang, Dmytro O. Kryshtal, Kyungsoo Kim, Shan Parikh, Adrian Gabriel Cadar, Kevin Richard Bersell, Huan He, Jose R. Pinto, Bjorn C. Knollmann
Journal: Journal of the American College of Cardiology (2017)
Tuberculin skin test conversion and primary progressive tuberculosis disease in the first 5 years of life: a birth cohort study from Cape Town, South Africa
Authors: Leonardo Martinez, David M le Roux, Whitney Barnett, Attie Stadler, Mark P Nicol, Heather J Zar
Journal: The Lancet Child & Adolescent Health (2017)

Tuberculosis is a leading cause of global childhood mortality. However, the epidemiology and burden of tuberculosis in infancy is not well understood. We aimed to investigate tuberculin skin test conversion and tuberculosis in the Drakenstein Child Health study, a South African birth cohort in a community in which tuberculosis incidence is hyperendemic.In this prospective birth cohort study, we enrolled pregnant women older than 18 years who were between 20 and 28 weeks' gestation and who were attending antenatal care in a peri-urban, impoverished South African setting. We followed up their children for tuberculosis from birth until April 1, 2017, or age 5 years. All children received BCG vaccination at birth. Tuberculin skin tests were administered to children at 6, 12, 24, 36, 48, and 60 months of age, and at the time of a lower respiratory tract infection. An induration reaction of 10 mm or more was considered to be a tuberculin skin test conversion. To prevent boosting, we censored children with a reactive, negative tuberculin skin test.Among 915 mother-child pairs (201 [22%] HIV-positive mothers and two [<1%] HIV-positive children), 147 (16%) children had tuberculin skin test conversion, with increasing cumulative hazard with age (0·08 at 6 months, 0·17 at 12 months, 0·22 at 24 months, and 0·37 at age 36 months). For every 100 child-years, the incidence was 11·8 (95% CI 10·0-13·8) for tuberculin skin test conversion, 2·9 (2·4-3·7) for all diagnosed tuberculosis, and 0·7 (0·4-1·0) for microbiologically confirmed tuberculosis. Isoniazid preventive therapy was effective in averting disease progression (adjusted hazard ratio 0·22, 95% CI 0·08-0·63; p<0·0001). Children with a lower respiratory tract infection were significantly more likely to also have tuberculosis than were those without one (2·27, 1·42-3·62; p<0·0001).Greater focus should be placed on the first years of life as a period of high burden of transmission and clinical expression of tuberculosis infection and disease. Multifaceted interventions, such as isoniazid preventive therapy and tuberculosis screening of infants with LRTIs, beginning early in life, are needed in high-burden settings.Bill & Melinda Gates Foundation, Medical Research Council South Africa, and National Research Foundation South Africa.
The role of confocal laser endomicroscopy in assessing mucosal healing in patients with ulcerative proctitis
Authors: Cristian Gheorghe, Gabriel Becheanu, Razvan Iacob, Bogdan Cotruta, Anca Dimitriu
Journal: Endoscopy (2017)

See also: Endocytoscopy can be used to assess histological healing in ulcerative colitisEndoscopy 2017; 49(06): 560-563DOI: 10.1055/s-0043-106556 See also: Reply to Gheorghe et al.Endoscopy 2017; 49(12): 1286-1286DOI: 10.1055/s-0043-120443