tbuckley/cabot-search huggingface dataset:
Impact of crizotinib on patient-reported general health status compared with chemotherapy in patients with no prior systemic treatment for advanced non-squamous <i>ALK</i>-positive non-small cell lung cancer (NSCLC).
Authors: Enriqueta Felip, Fiona Helen Blackhall, Tony Mok, Federico Cappuzzo, Keith D. Wilner, Arlene Reisman, Shrividya Iyer, Benjamin J. Solomon
Journal: Journal of Clinical Oncology (2015)

8101 Background: The present analysis compares patient-reported general health status between crizotinib and chemotherapy in patients who had received no prior systemic treatment for advanced non-squamous ALK-positive NSCLC. Methods: Patients in the phase III PROFILE 1014 study (Pfizer; NCT01154140) were randomized to crizotinib (250 mg PO BID n = 172) or chemotherapy (pemetrexed 500 mg/m2 + cisplatin 75 mg/m2 or carboplatin AUC 5–6; all IV q3w for ≤ 6 cycles; n = 171). Patient-reported outcomes were assessed at baseline, day 1 of each cycle and end of treatment using EQ-5D, a standardized measure of health status that includes a descriptive system comprising 5 dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression rated at 3 levels (no, some, or extreme problems) and a single index score for health status (range 0 [dead] to 1 [full health]) calculated using a standard algorithm. In addition, a visual analog scale (VAS) measured health status from '0' (worst imaginable) to '100' (best imaginable). Repeated measures mixed-effects analyses were performed to compare overall VAS and index scores between treatments, controlling for baseline. Results: The mean (SD) scores at baseline were comparable between crizotinib and chemotherapy for VAS (70.78 [19.65] vs (66.64 [21.89]) and EQ-5D index scores (0.72 [0.30]) vs (0.71 [0.26]).The proportion of patients reporting presence of a problem at baseline for crizotinib and chemotherapy respectively were: mobility (27% vs 34%), self-care (13% vs 13%), usual activities (44% vs 46%), pain (56% vs 68%), and anxiety/depression (41% vs 39%). The overall mean VAS scores on treatment were statistically significantly higher (p < 0.05) in the crizotinib arm compared with the chemotherapy arm. The overall mean EQ-5D index scores on treatment were significantly greater (p < 0.001) for crizotinib [0.81] compared with chemotherapy [0.72]. Conclusions: Treatment with crizotinib leads to significantly greater overall general health status scores compared to chemotherapy in in advanced non-squamous ALK-positive NSCLC patients. Clinical trial information: NCT01154140.
Minimally Invasive Lung Cancer Surgery Performed by Thoracic Surgeons as Effective as Thoracotomy
Authors: Daniel J. Boffa, Andrzej S. Kosinski, Anthony P. Furnary, Sunghee Kim, Mark W. Onaitis, Betty C. Tong, Patricia A. Cowper, Jessica R. Hoag, Jeffrey P. Jacobs, Cameron D. Wright, Joe B. Putnam, Felix G. Fernandez
Journal: Journal of Clinical Oncology (2018)

Purpose The prevalence of minimally invasive lung cancer surgery using video-assisted thoracic surgery (VATS) has increased dramatically over the past decade, yet recent studies have suggested that the lymph node evaluation during VATS lobectomy is inadequate. We hypothesized that the minimally invasive approach to lobectomy for stage I lung cancer resulted in a longitudinal outcome that was not inferior to thoracotomy. Patients and Methods Patients > 65 years of age who had undergone lobectomy for stage I lung cancer between 2002 and 2013 were analyzed within the Society of Thoracic Surgeons General Thoracic Surgery Database, which had been linked to Medicare data, as part of a retrospective-cohort, noninferiority study. Results A total of 10,597 patients with clinical stage I lung cancer who underwent lobectomy were evaluated (4,448 patients underwent thoracotomy, and 6,149 underwent VATS). VATS patients had a more favorable distribution of all health-related variables, including pulmonary function (59% of VATS patients had intact spirometry v 51% of thoracotomy patients; P < .001). Cox proportional hazards models were performed over two eras to account for an evolving practice standard. The mortality risk associated with the VATS approach was not greater than thoracotomy in either the earlier era (2002 to 2008; hazard ratio, 0.97; 95% CI, 0.87 to 1.09; P = .62) or the more recent era (2009 to 2013; hazard ratio, 0.84; 95% CI, 0.75 to 0.93; P < .001). Kaplan-Meier survival estimates of 2,901 propensity-matched VATS-thoracotomy pairs demonstrated that the 4-year survival associated with VATS (68.6%) was modestly superior to thoracotomy (64.8%; P = .003). The analyses detailed above were replicated in a separate cohort of pathologic stage I patients with similar findings. Conclusion The long-term efficacy of lobectomy for stage I lung cancer performed using the VATS approach by board-certified thoracic surgeons does not seem to be inferior to that of thoracotomy.
The role of thymidylate synthase as a biomarker for pemetrexed sensitivity in lung cancer
Authors: Hiroaki Ozasa, Ken Maeno, Tetsuya Oguri, Yuji Bessho, Mikinori Miyazaki, Yuko Takano, Hiroyoshi Maeda, Shigeki Sato, Ryuzo Ueda
Journal: Cancer Research (2007)

2316   Pemetrexed is promising argent for non-small cell lung cancer (NSCLC) chemotherapy; however, the biomarkers for predicting sensitivity to this argent have not been fully examined. In the present study we measured the expression level of thymidylate synthase (TS), a major target of pemetrexed, reduced folate carrier (RFC) and folylpolyglutamate synthase (FPGS) in lung cancer cell lines and the sensitivity to pemetrexed. The gene expression of TS was significantly correlated with the concentration of pemertrexed for 50% cell survival in 11 non-small cell lung cancer cell lines (r=0.624, p
Nanodiamonds as “artificial proteins”: Regulation of a cell signalling system using low nanomolar solutions of inorganic nanocrystals
Authors: Lukas Balek, Marcela Buchtova, Michaela Kunova Bosakova, Miroslav Varecha, Silvie Foldynova-Trantirkova, Iva Gudernova, Iva Vesela, Jan Havlik, Jitka Neburkova, Stuart Turner, Mateusz Adam Krzyscik, Malgorzata Zakrzewska, Lars Klimaschewski, Peter Claus, Lukas Trantirek, Petr Cigler, Pavel Krejci
Journal: Biomaterials (2018)

The blocking of specific protein-protein interactions using nanoparticles is an emerging alternative to small molecule-based therapeutic interventions. However, the nanoparticles designed as “artificial proteins” generally require modification of their surface with (bio)organic molecules and/or polymers to ensure their selectivity and specificity of action. Here, we show that nanosized diamond crystals (nanodiamonds, NDs) without any synthetically installed (bio)organic interface enable the specific and efficient targeting of the family of extracellular signalling molecules known as fibroblast growth factors (FGFs). We found that low nanomolar solutions of detonation NDs with positive ζ-potential strongly associate with multiple FGF ligands present at sub-nanomolar concentrations and effectively neutralize the effects of FGF signalling in cells without interfering with other growth factor systems and serum proteins unrelated to FGFs. We identified an evolutionarily conserved FGF recognition motif, ∼17 amino acids long, that contributes to the selectivity of the ND-FGF interaction. In addition, we inserted this motif into a de novo constructed chimeric protein, which significantly improved its interaction with NDs. We demonstrated that the interaction of NDs, as purely inorganic nanoparticles, with proteins can mitigate pathological FGF signalling and promote the restoration of cartilage growth in a mouse limb explant model. Based on our observations, we foresee that NDs may potentially be applied as nanotherapeutics to neutralize disease-related activities of FGFs in vivo.
Abstract 13936: The Role of Telehomecare in Blood Pressure Monitoring for Heart Failure Patients
Authors: Yeva Sahakyan, Lusine Abrahamyan, Nida Shahid, Aleksandra Stanimirovic, Welson Ryan, Petros Pechlivanoglou, Nicholas Mitsakakis, Murray Krahn, Valeria E Rac
Journal: Circulation (2016)

Introduction: Introduced in 2007 by the Ontario Telemedicine Network, the Telehomecare program provides monitoring of patient’s parameters and coaching sessions. To date, no study evaluated the effect of Telehomecare on patient clinical monitoring parameters in Ontario. Hypothesis: We hypothesized that blood pressure (BP) would be improved among heart failure patients participating in the Telehomecare. Methods: We applied a time series study design to analyze patients’ BP values, transmitted via telemonitoring devices on a daily basis. The cohort included heart failure patients enrolled in the Telehomecare program from July 2012 to July 2015. The outcome of interest was the change in average (biweekly) systolic and diastolic BP levels over the 6-month program duration. The baseline BP levels were defined as the average of daily measurements for the first 2-week period after enrolment. Data was analysed by repeated measures with generalized linear mixed model procedures in SAS. Sensitivity analyses were conducted for per-protocol cohort, defined as those who had fully completed 6-month program duration. Results: Overall we analyzed data for 2186 heart failure patients (50% women) with average age of 76.0±11.4 years. At baseline, the systolic and diastolic BP levels were 129.2 ±19.8 and 70.4 ±12.7 mm Hg respectively. Over 6-month period systolic BP decreased by -3.5 mm Hg (95% CI: -4.2 to -2.8) and diastolic by -2.5 mm Hg (95% CI: -3.0 to -2.0). At baseline, one third of the patients (n=721) had elevated BP with an average systolic BP of 150.9±10.15 mm Hg and diastolic BP of 78.3±14.1 mm Hg. In a subgroup analyses of this population the reduction in systolic BP was -12.3 mm Hg (95% CI: -13.4 to -11.1) and in diastolic BP was -6.9 mm Hg (95% CI: -7.8 to -6.0) adjusted for age and gender. Similar changes were observed in per-protocol cohort. Conclusions: The systolic and diastolic BP levels significantly decreased in patients with heart failure enrolled in the Telehomecare program. These changes were more pronounced in patients with uncontrolled BP at program entry. Hence Telehomecare program might be a promising tool to help patients in BP management
ECMO for Severe ARDS
Authors: C. Corey Hardin, Kathryn Hibbert
Journal: New England Journal of Medicine (2018)

The acute respiratory distress syndrome (ARDS), which is characterized by severe hypoxemic respiratory failure, affects as many as 10% of patients in the intensive care unit and is a common reason for the use of therapeutic mechanical ventilation.1 On the basis of results of landmark clinical trials, there is substantial consensus around an initial approach to ARDS that combines invasive mechanical ventilation with limited tidal volumes,2 the use of positive end-expiratory pressure (PEEP) to prevent derecruitment (the collapse of small airways and alveoli),3 and conservative fluid management.4 In patients with severe ARDS, defined as a ratio of partial pressure of . . .
Phase I Study of Oncolytic Vaccinia Virus GL-ONC1 in Patients with Peritoneal Carcinomatosis
Authors: Ulrich M. Lauer, Martina Schell, Julia Beil, Susanne Berchtold, Ursula Koppenhöfer, Jörg Glatzle, Alfred Königsrainer, Robert Möhle, Dominik Nann, Falko Fend, Christina Pfannenberg, Michael Bitzer, Nisar P. Malek
Journal: Clinical Cancer Research (2018)

Purpose: Peritoneal carcinomatosis is common in advanced tumor stages or disease recurrence arising from gastrointestinal cancers, gynecologic malignancies, or primary peritoneal carcinoma. Because current therapies are mostly ineffective, new therapeutic approaches are needed. Here, we report on a phase I study designed to assess safety, MTD, and antitumor activity of intraperitoneal administration of oncolytic vaccinia virus GL-ONC1 in advanced stage peritoneal carcinomatosis patients.Patients and Methods: GL-ONC1 was administered intraperitoneally every 4 weeks for up to four cycles at three different dose levels (107-109 pfu) following a standard 3+3 dose escalation design. GL-ONC1 was infused via an indwelling catheter that enabled repetitive analyses of peritoneal fluid biopsies. The primary study objective was safety of GL-ONC1 according to Common Terminology Criteria for Adverse Events, version 4.0 (CTCAEv4.0).Results: Patients with advanced-stage peritoneal carcinomatosis (n = 7) or advanced peritoneal mesothelioma (n = 2) received 24 doses of GL-ONC1. Adverse events were limited to grades 1-3, including transient flu-like symptoms and increased abdominal pain, resulting from treatment-induced peritonitis. No DLT was reported, and the MTD was not reached. Furthermore, no signs of viral shedding were observed. Importantly, in 8 of 9 study patients, effective intraperitoneal infections, in-patient replication of GL-ONC1, and subsequent oncolysis were demonstrated in cycle 1. All patients developed neutralizing activities against GL-ONC1.Conclusions: GL-ONC1 was well tolerated when administered into the peritoneal cavity of patients with advanced stage peritoneal carcinomatosis. Efficient tumor cell infection, in-patient virus replication, and oncolysis were limited to treatment cycle 1 (ClinicalTrials.gov number, NCT01443260). Clin Cancer Res; 24(18); 4388-98. ©2018 AACR.
An immune-beige adipocyte communication via nicotinic acetylcholine receptor signaling
Authors: Heejin Jun, Hui Yu, Jianke Gong, Juan Jiang, Xiaona Qiao, Eric Perkey, Dong-il Kim, Margo P. Emont, Alexander G. Zestos, Jung-Sun Cho, Jianfeng Liu, Robert T. Kennedy, Ivan Maillard, X. Z. Shawn Xu, Jun Wu
Journal: Nature Medicine (2018)
HOUT-18. SAFETY OF COMMERCIAL AIRFLIGHT IN PATIENTS WITH BRAIN TUMORS – A CASE SERIES
Authors: Michelle Phillips, Marlon Garzo Saria, Amy Eisenberg, Daniel Kelly, Garni Barkhoudarian
Journal: Neuro-Oncology (2017)

Patients with intracranial masses are often advised to avoid airflight due to concerns of worsening neurological symptoms. However, many patients often travel to tertiary care neuro-oncology centers and some travel internationally. This study assesses the safety of commercial airflight for brain tumor patients without severe or progressive neurological deficits. Patients that had traveled to our institution for surgical evaluation via commercial airflight from 2014-2017 were identified. An electronic survey was administered (RedCap) and flight duration, aircraft type, presenting symptoms and new or worsened peri-flight symptoms were queried. Severity was assessed using visual analogue scale (VAS). Significant change of symptoms was determined to be greater than 25%. Demographics and clinical history obtained from electronic medical records. Providence Health System IRB: 16-168. 40 patients were enrolled and completed the study. Patients had an average age of 47.7years and were 65% female. Pathology included parasellar tumors (60%), Meningiomas (20%), Metastatic tumors (5%), Gliomas (5%), Pineal tumor (5%), cerebello-pontine tumor (5%). Average flight duration: 6.5 h (range 1-17h). Average tumor volume 11.1cc and average maximal dimension 2.5cm. Nine (22.5%) patients developed worsened symptoms during airflight. These include headaches 3/19 (15.8%), fatigue 3/14 (21.4%), dizziness 3/5 (60%) and ear pain 3/3 (100%). Six patients (66.7%) had sustained worsened symptoms after airflight. Only one patient had symptoms that worsened to a severe level (transiently during flight – VAS 9/10). There were no permanent neurological deficits related to airflight. There was no correlation with tumor size, flight duration, and peri-flight corticosteroid usage. No patient with completely asymptomatic tumors developed new symptoms during flight. Patients with brain tumors traveling via commercial airflight can do so with acceptable symptom exacerbation. No permanent neurological deficits were noted due to air travel.
Development of a Risk Score Based on Aortic Calcification to Predict 1-Year Mortality After Transcatheter Aortic Valve Replacement
Authors: Pierre Lantelme, Hélène Eltchaninoff, Muriel Rabilloud, Géraud Souteyrand, Marion Dupré, Marco Spaziano, Marc Bonnet, Clément Becle, Benjamin Riche, Eric Durand, Erik Bouvier, Jean-Nicolas Dacher, Pierre-Yves Courand, Lucie Cassagnes, Eduardo E. Dávila Serrano, Pascal Motreff, Loic Boussel, Thierry Lefèvre, Brahim Harbaoui
Journal: JACC. Cardiovascular imaging (2018)
Trends in Antiretroviral Therapy Eligibility and Coverage Among Children Aged &lt;15 Years with HIV Infection — 20 PEPFAR-Supported Sub-Saharan African Countries, 2012–2016
Authors: Amanda Burrage, Monita Patel, Kelsey Mirkovic, Eric Dziuban, Wondimu Teferi, Laura Broyles, Emilia Rivadeneira
Journal: MMWR Morbidity and Mortality Weekly Report (2018)

Rapid disease progression and associated opportunistic infections contribute to high mortality rates among children aged <15 years with human immunodeficiency virus (HIV) infection (1). Antiretroviral therapy (ART) has decreased childhood HIV-associated morbidity and mortality rates over the past decade (2). As accumulating evidence revealed lower HIV-associated mortality with early ART initiation, the World Health Organization (WHO) guidelines broadened ART eligibility for children with HIV infection (2). Age at ART initiation for children with HIV infection expanded sequentially in the 2010, 2013, and 2016 WHO guidelines to include children aged <2, <5, and <15 years, respectively, regardless of clinical or immunologic status (3-5). The United States President's Emergency Plan for AIDS Relief (PEPFAR) has supported ART for children with HIV infection since 2003 and, informed by the WHO guidelines and a growing evidence base, PEPFAR-supported countries have adjusted their national pediatric guidelines. To understand the lag between guideline development and implementation, as well as the ART coverage gap, CDC assessed national pediatric HIV guidelines and analyzed Joint United Nations Programme on HIV and AIDS (acquired immunodeficiency syndrome; UNAIDS) data on children aged <15 years with HIV infection and the numbers of these children on ART. Timeliness of WHO pediatric ART guideline adoption varied by country; >50% of children with HIV infection are not receiving ART, underscoring the importance of strengthening case finding and linkage to HIV treatment in pediatric ART programs.
Amyloid-β (1-40) and Mortality in Patients With Non–ST-Segment Elevation Acute Coronary Syndrome
Authors: Kimon Stamatelopoulos, Matthias Mueller-Hennessen, Georgios Georgiopoulos, Marco Sachse, Jasper Boeddinghaus, Kateryna Sopova, Aikaterini Gatsiou, Carolin Amrhein, Moritz Biener, Mehrshad Vafaie, Fani Athanasouli, Dimitrios Stakos, Konstantinos Pateras, Raphael Twerenbold, Patrick Badertscher, Thomas Nestelberger, Stefanie Dimmeler, Hugo A. Katus, Andreas M. Zeiher, Christian Mueller, Evangelos Giannitsis, Konstantinos Stellos
Journal: Annals of Internal Medicine (2018)

Background: Amyloid-β (1-40) (Aβ40) is implicated in mechanisms related to plaque destabilization and correlates with adverse outcomes in stable coronary artery disease. Objective: To determine the prognostic and reclassification value of baseline circulating levels of Aβ40 after adjustment for the Global Registry of Acute Coronary Events (GRACE) score, which is widely recommended for risk stratification in non–ST-segment elevation acute coronary syndrome (NSTE-ACS). Design: Retrospective cohort study using data from 2 independent prospective cohorts, the Heidelberg study (n = 1145) and the validation multicenter international APACE (Advantageous Predictors of Acute Coronary Syndrome Evaluation) study (n = 734). Setting: Academic hospitals in 7 European countries. Participants: Patients with adjudicated NSTE-ACS followed for a median of 21.9 and 24.9 months in the Heidelberg and APACE studies, respectively. Measurements: All-cause mortality was the primary end point. Results: Amyloid-β (1-40) was associated with mortality after multivariate adjustment for age, sex, diabetes mellitus, high-sensitivity cardiac troponin T and C-reactive protein, revascularization, and ACS type (Heidelberg cohort hazard ratio [HR] for 80th vs. 20th percentiles, 1.66 [95% CI, 1.06 to 2.61; P = 0.026]; APACE cohort HR, 1.50 [CI, 1.15 to 1.96; P = 0.003]). It was also associated with mortality after adjustment for the GRACE score (Heidelberg cohort HR for 80th vs. 20th percentiles, 1.11 [CI, 1.04 to 1.18; P = 0.001]; APACE cohort HR, 1.39 [CI, 1.02 to 1.88; P = 0.036]). Amyloid-β (1-40) correctly reclassified risk for death over the GRACE score (net reclassification index, 33.4% and 47.1% for the Heidelberg and APACE cohorts, respectively) (P < 0.05). Limitation: At low concentrations of Aβ40, dose–response associations with mortality differed between cohorts, possibly because of varying blood preparations used to measure Aβ40. Conclusion: Circulating Aβ40 is a predictor of mortality and improves risk stratification of patients with NSTE-ACS over the GRACE score recommended by clinical guidelines. The clinical application of Aβ40 as a novel biomarker in NSTE-ACS should be further explored and validated. Primary Funding Source: German Cardiac Society.
Moral externalization may precede, not follow, subjective preferences
Authors: Artem Kaznatcheev, Thomas R. Shultz
Journal: Behavioral and Brain Sciences (2018)

Abstract We offer four counterarguments against Stanford's dismissal of moral externalization as an ancestral condition, based on requirements for ancestral states, mismatch between theoretical and empirical games, passively correlated interactions, and social interfaces that prevent agents’ knowing game payoffs. The fact that children's externalized phenomenology precedes their discovery of subjectivized phenomenology also suggests that externalized phenomenology is an ancestral condition.
Overcoming overuse: the way forward is not standing still—an essay by Steven Woloshin and Lisa M Schwartz
Authors: Steven Woloshin, Lisa M Schwartz
Journal: BMJ (2018)

Overdiagnosis and overtreatment are real, wasteful, and harmful, and doctors have an ethical duty to act, say <b>Steven Woloshin</b> and <b>Lisa M Schwartz</b>, responding to recent claims otherwise in the <i>New England Medical Journal</i>
Incorporating Physical Function and Cognition Into Mortality Risk Assessment for Acute Myeloid Leukemia—Reply
Authors: Mohamed L. Sorror, Barry E. Storer, Elihu H. Estey
Journal: JAMA Oncology (2018)

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