tbuckley/cabot-search huggingface dataset:
Phase III study of cisplatin (P) plus etoposide (E) with concurrent chest radiation (XRT) followed by docetaxel (D) vs. observation in patients (pts) with stage III non-small cell lung cancer (NSCLC): An interim toxicity analysis of consolidation therapy
Authors: P. M. Bedano, M. Neubauer, R. Ansari, R. Govindan, L. H. Einhorn, D. Bruetman, A. White, T. Breen, B. Juliar, N. Hanna
Journal: Journal of Clinical Oncology (2006)

7043 Background: Concurrent chemo radiotherapy is the standard treatment for pts with unresectable stage III NSCLC. A previously reported phase II study (Gandara et al J Clin Oncol 2003) suggests that consolidation D after concurrent PE/XRT may further improve survival. HOG LUN01–24, is an ongoing phase III clinical trial comparing chemo radiation. A preliminary analysis of the differences in toxicities between PE/XRT with or without consolidation D was performed. Methods: Eligible pts had previously untreated, unresectable stage III NSCLC, ECOG PS 0–1 at time of study entry (and PS 0–2 at the time of randomization), ≤ 5% weight loss in preceding 3 months, FEV-1 &gt; 1 L. Treatment consisted of P 50 mg/m 2 days 1, 8, 29, 36 with E 50 mg/m 2 days 1–5 and 29–33, given concurrently with chest XRT to 5,940 cGy (180 cGy/day) beginning on day 1. Non-progressive pts were randomized (4–8 weeks after completing PE/XRT) to receive D 75 mg/m 2 iv every 21 days for 3 cycles vs. observation. We report an interim toxicity analysis associated to consolidation D. Results: From 3/02 to 12/05 220 have been registered and 149 pts have been randomized to consolidation D (n=73) or observation (n=76). Median age was 63.6 years (range 33–86); male/female 34.1%/65.9%; PS 0/1 at study entry 59.1%/40.9%; stage III A/B 40.6%/59.4%; 50.2% had FEV-1 &gt; 2 (range 1–4.2); 44.3% were current smokers. Randomized pts have PS 0/1/2 44.3%/53%/2.7. Selected grade 3/4 toxicities associated to D include: neutropenia 23.3%, febrile neutropenia 8.2%, and pulmonary toxicity 9.6%. In addition, 26.7% of pts had dose modifications or delays on D arm, 45.2% had at least one grade 3/4 toxicity and 20.5% were hospitalized due to D-related toxicity, including 4 pts (5.5%) whose death was considered therapy related. Conclusions: Concurrent PE/XRT followed by consolidation D is associated with a high rate of grade 3/4 toxicities and hospitalizations, including treatment-related deaths. Updated toxicity data will be presented at the ASCO meeting. Whether consolidation D confers a survival advantage is not yet known. [Table: see text]
Nomograms to predict serious adverse events (SAEs) in patients (pts) enrolled in phase II clinical trials of molecularly targeted agents (MTAs)
Authors: G. R. Pond, L. L. Siu, M. J. Moore, A. M. Oza, H. Hirte, E. Winquist, G. Goss, G. Hudes, P. Degendorfer, C. A. Townsley
Journal: Journal of Clinical Oncology (2007)

6601 Background: The likelihood of experiencing a SAE in clinical trials with a MTA is of interest for clinicians discussing treatment options. Adverse event data from clinical trials in the Princess Margaret Hospital Phase II Consortium [PMH2C] database were analyzed to address this question. Methods: All pts in the PMH2C database treated at the phase II dose level with either a MTA alone or in combination regimens since 2001 were included. Generalised estimating equations were used to construct optimal regression models predicting the increased/decreased odds of a SAE of all causalities (defined as a grade 3+ non-hematologic adverse event, or a grade 4+ hematologic adverse event) during the first cycle of treatment relative to a ‘reference’ pt. Nomograms were constructed to ease interpretation and internal validation explored using bootstrapping on trials larger than 35 pts. Results: 576 pts (median age=60, 55% male, ECOG PS 0:1:2=259:284:35) were accrued to 42 studies. In order of statistical significance, higher ECOG PS, increased LDH, decreased albumin, increased Charlson score, increased number of target lesions, not having prior radiotherapy and decreased age were predictive of increased odds of cycle 1 SAE. As an example, a 56-year old patient with ECOG 2, Charlson score=0, 5 target lesions, LDH=1.70x upper limit of normal [ULN], albumin=0.84xULN and no prior radiation would have ∼3 times increased odds of a SAE in cycle 1, compared to a 63-year old with ECOG 1, Charlson score=0, 1 target lesion, LDH=0.76xULN, albumin=0.68xULN and no prior radiation. Internal validation of the 4 largest studies indicated moderate-good accuracy (estimated area under the receiver operating characteristic curve = 0.57–0.86). Conclusions: A nomogram was produced allowing estimation of the increased odds of a SAE during cycle 1 of therapy in a phase II trial setting. Actual risk can then be further estimated by incorporating clinical judgment of risks for an average pt when given a particular MTA. This nomogram can potentially improve patient knowledge, risk estimates and the decision-making process. External validation of the model is still necessary to adequately assess model reliability. No significant financial relationships to disclose.
Clinical Relevance of Diagnostic Criteria for Hemophagocytic Lymphohistiocytosis (HLH) and Survival Outcome of Adult HLH Patients: A Single-Center Prospective Cohort Study
Authors: Joon Young Hur, Kang Kook Lee, Jun Ho Jang, Kihyun Kim, Chul Won Jung, Won Seog Kim, Seok Jin Kim
Journal: Blood (2018)
The prognostic value of β-catenin and LEF-1 expression in patients with gastric carcinoma.
Authors: Serap Kaya, Mahmut Gumus, Yesim Gurbuz, Suleyman Temiz, Devrim Cabuk, Ozgur Acikgoz, Kazim Uygun
Journal: Journal of Clinical Oncology (2012)

e14618 Background: Wnt signal transduction pathway plays an important role in carcinogenesis. Wnt signal transduction pathway is a key component of the β-catenin-TCF / LEF family of transcription factors interact with and activate the transcription of Wnt target genes. The aim of this study is to evaluate the prognostic value of β-katenin and LEF-1 expression in patients with operable gastric cancer and the relationship between demographic and histopathological variables. Methods: In this study, 82 gastric cancer patients treated with adjuvant treatment after operation and followed in Oncology Department between 2006-2010 were included. β-katenin and LEF-1 expression were examined by immunuhistochemical analysis in paraffin embedded tumor tissues of the patients. Results: In this study, median age was 56 (26-81) years and median follow up was 19 (4-61) months. Performance status (ECOG PS) were 0-1 in all patients. Men/women ratio was 53/29 (64.6/35.4%). Median disease free survival (DFS) time was 17 months (SE:3 95% CI: 11-23) in 19 months of follow up. 3 years DFS rate was 39.7%. In all patients group, median overall survival (OS) time was 28 months (SE:4 95% CI: 20-36) and 3 years OS rate was 41,2%. There was no statistical correlation between β-catenin and LEF-1 expression and age, gender, performance status, tumor localization, T and N stage, lymphovascular, perinoral invasion, grade and operation type (&gt;0.05). In addition, there was also no correlation between β-catenin and LEF-1 expression. According to univariate analysis, we did not find significant effect on age, gender, T stage, lymphovascular, perinoral invasion, grade and operation type on overall survival (p&gt;0.05). Good performans status (ECOG 0), tumor infiltration without diffuse type like linitis plastica, and lower N stage had positive effect on survival (p=0.04, 0.033 and 0.005, respectively). In multivariate cox regression analysis, only N stage was found as an independent prognostic factor (p&lt;0.05). Conclusions: In this study group, we found that the only N stage as an independent prognostic factor. Demographic features of the patients, histopathological characteristics other than N stage, β-catenin and LEF-1 prognostic effects have not been shown.
Characteristics of the Quality Improvement Content of Cardiac Catheterization Peer Reviews in the Veterans Affairs Clinical Assessment, Reporting, and Tracking Program
Authors: Jacob A. Doll, Mary E. Plomondon, Stephen W. Waldo
Journal: JAMA Network Open (2019)

<h3>Importance</h3> Peer review is recommended for quality assessment in all cardiac catheterization programs, but, to our knowledge, the content of peer reviews and the potential for quality improvement has not been described. <h3>Objective</h3> To characterize the quality improvement content of cardiac catheterization peer reviews. <h3>Design, Setting, and Participants</h3> This quality improvement study used retrospective case review of diagnostic angiography and percutaneous coronary intervention procedures to characterize the major adverse event review process of the US Department of Veterans Affairs Clinical Assessment, Reporting, and Tracking (CART) program from January 1, 2012, to December 31, 2016. Data review and analysis took place from November 2017 to August 2018. <h3>Main Outcomes and Measures</h3> Percentage of peer reviews reporting substandard care and opportunities for quality improvement. <h3>Results</h3> A total of 196 643 diagnostic coronary angiograms and 62 576 percutaneous coronary interventions were performed in the Department of Veterans Affairs. Of these, 168 (0.1%) were triggered for review because of a self-reported major adverse event during the procedure. Of 152 cases with complete peer review data, care was adjudicated as not meeting the standard of care in 25 cases (16.4%). Concerns about operator judgment were identified in 46 cases (30.3%), about case selection in 26 (17.1%), about trainee supervision in 21 (13.8%), and about technical performance in 46 (30.3%). Reviewers made recommendations to improve operator performance in 63 cases (41.4%) and catheterization laboratory or hospital processes in 58 (38.2%). <h3>Conclusions and Relevance</h3> While substandard care is infrequently identified in peer review of catheterization laboratory complications in the Department of Veterans Affairs, the process often generates recommendations for quality improvement. Peer review programs should focus on identifying quality improvement opportunities and providing meaningful feedback to operators.
Myocardial Injury in the Era of High-Sensitivity Cardiac Troponin Assays
Authors: Cian P. McCarthy, Inbar Raber, Andrew R. Chapman, Yader Sandoval, Fred S. Apple, Nicholas L. Mills, James L. Januzzi
Journal: JAMA Cardiology (2019)

<h3>Importance</h3> Traditionally, elevated troponin concentrations were synonymous with myocardial infarction. But with improvements in troponin assays, elevated concentrations without overt myocardial ischemia are now more common; this is referred to as<i>myocardial injury</i>. Physicians may be falsely reassured by the absence of myocardial ischemia; however, recent evidence suggests that myocardial injury is associated with even more detrimental outcomes. Accordingly, this article reviews the definition, epidemiology, differential diagnosis, diagnostic evaluation, and management of myocardial injury. <h3>Observations</h3> Current epidemiological evidence suggests that myocardial injury without overt ischemia represents about 60% of cases of abnormal troponin concentrations when obtained for clinical indications, and 1 in 8 patients presenting to the hospital will have evidence of myocardial injury. Myocardial injury is a concerning prognosis; the 5-year mortality rate is approximately 70%, with a major adverse cardiovascular event rate of 30% in the same period. The differential diagnosis is broad and can be divided into acute and chronic precipitants. The initial workup involves an assessment for myocardial ischemia. If infarction is ruled out, further evaluation includes a detailed history, physical examination, laboratory testing, a 12-lead electrocardiogram, and (if there is no known history of structural or valvular heart disease) an echocardiogram. Unfortunately, no consensus exists on routine management of patients with myocardial injury. Identifying and treating the underlying precipitant is the most practical approach. <h3>Conclusion and Relevance</h3> Myocardial injury is the most common cause of abnormal troponin results, and its incidence will likely increase with an aging population, increasing prevalence of cardiovascular comorbidities, and greater sensitivity of troponin assays. Myocardial injury represents a challenge to clinicians; however, given its serious prognosis, it warrants a thorough evaluation of its underlying precipitant. Future strategies to prevent and/or manage myocardial injury are needed.
Effectiveness of EV-A71 vaccination in prevention of paediatric hand, foot, and mouth disease associated with EV-A71 virus infection requiring hospitalisation in Henan, China, 2017–18: a test-negative case-control study
Authors: Yu Li, Yonghong Zhou, Yibing Cheng, Peng Wu, Chongchen Zhou, Peng Cui, Chunlan Song, Lu Liang, Fang Wang, Qi Qiu, Chun Guo, Mengyao Zeng, Lu Long, Benjamin J Cowling, Hongjie Yu
Journal: The Lancet Child & Adolescent Health (2019)
Abstract P096: The Genetics Architecture of the Serum Metabolome
Authors: Zhe Wang, Bing Yu, Paul S De Vries, Elena V Feofanova, Fuli Yu, Richard A Gibbs, Alanna C Morrison, Eric Boerwinkle
Journal: Circulation (2017)

Introduction: The metabolome is a collection of small molecules in a biologic sample, and may serve as biomarkers or predictors of heart disease. Whole genome sequence analysis offers the opportunity to investigate rare and low-frequency annotated variants across the human genome. We used whole genome sequence analysis to characterize the genetic architecture of the serum metabolome. Methods: Whole genome sequencing and measurement (chromotagraphy and mass spectroscopy) of 245 serum metabolites were done in 1,458 European Americans and 1,679 African Americans from the Atherosclerosis Risk in Communities (ARIC) study, and these data were used to perform a trans-ethnic meta-analysis. Common variants (MAF&gt;5%) were analyzed individually using an additive genetic model. Rare and low-frequency protein-altering variants (MAF≤5%) were aggregated by genes. In order to determine the contribution of regulatory and non-protein coding regions of the genome, we conducted aggregate tests across the entire genome using a 4kb sliding window as well as in predefined regulatory elements, which includs enhancers, promoter, and 3’ and 5’ untranslated region of a gene. Results: We identified 119 significant associations between genetic variants and metabolite levels (significance threshold p&lt;2.0*10 -10 for single variants, p&lt;2.9х10 -10 for aggregate tests), of which 49 were novel, including genes involved in known Mendelian conditions, protein biological processes, and disease related pathways. Six genes ( DMGDH, AGA, ACY1, PRODH, DDC and CPS1 ) causing rare inborn errors of metabolism were associated with amino acid levels in the general population. A predicated regulatory variant in the AGA gene, encoding a protein involved in asparagine generation, was associated with serum asparagine levels independent of any coding variants in this gene. Seven genes ( ABCC2, PKD2L1, SLC10A1, FDX1, CYP3A43, UGT2B15 and SULT2A1 ) related to lipid-related metabolite levels were identified, whose gene products are involved in secretion, channeling and transportation. Analysis of regulatory regions unraveled associations between three steroid lipids and a member of the cytochrome P450 family, CYP3A43 . Five genes within the kinin-kallikrein pathway were identified to be related to small peptide levels, including KLKB1 , KNG1 , F12 , ACE and CPN1 . Variants in CPN1 , which is known to bind to fibrinogen, were associated with DSGEGDFXAEGGGVR, a peptide which is produced during fibrinogen to fibrin conversion. Conclusion: This study outlines an approach to characterize the genetic architecture of the human serum metabolome and shows that sequence variants affect multiple human metabolites. Using the principle of Mendelian randomization, the next step is to determine whether any of these metabolites are in causal pathways to disease.
Level of evidence used in recommendations by the National Comprehensive Cancer Network (NCCN) guidelines beyond Food and Drug Administration approvals
Authors: R. Kurzrock, L.A. Gurski, R.W. Carlson, D.S. Ettinger, S.M. Horwitz, S.K. Kumar, L. Million, M. von Mehren, A.B. Benson
Journal: Annals of Oncology (2019)

A previous analysis of 113 National Comprehensive Cancer Network® (NCCN®) recommendations reported that NCCN frequently recommends beyond Food and Drug Administration (FDA)-approved indications (44 off-label recommendations) and claimed that the evidence for these recommendations was weak.
IgG4-related disease in the Japanese population: a genome-wide association study
Authors: Chikashi Terao, Masao Ota, Takeshi Iwasaki, Masahiro Shiokawa, Shuji Kawaguchi, Katsutoshi Kuriyama, Takahisa Kawaguchi, Yuzo Kodama, Izumi Yamaguchi, Kazushige Uchida, Koichiro Higasa, Motohisa Yamamoto, Kensuke Kubota, Shujiro Yazumi, Kenji Hirano, Yasufumi Masaki, Hiroyuki Maguchi, Tomoki Origuchi, Shoko Matsui, Takahiro Nakazawa, Hideyuki Shiomi, Terumi Kamisawa, Osamu Hasebe, Eisuke Iwasaki, Kazuo Inui, Yoshiya Tanaka, Koh-ichi Ohshima, Takashi Akamizu, Shigeo Nakamura, Seiji Nakamura, Takako Saeki, Hisanori Umehara, Tooru Shimosegawa, Nobumasa Mizuno, Mitsuhiro Kawano, Atsushi Azumi, Hiroki Takahashi, Tsuneyo Mimori, Yoichiro Kamatani, Kazuichi Okazaki, Tsutomu Chiba, Shigeyuki Kawa, Fumihiko Matsuda, Atsushi Kanno, Yoshihiro Okabe, Shinji Katsushima, Tetsuro Inokuma, Yukitaka Yamashita, Yoshitaka Nakai, Takayoshi Nishino, Kozo Kajimura, Mitsushige Shibatoge, Naoki Kanda, Akio Ido, Masaya Ohana, Ichiro Moriyama, Hiroshi Tatsuta, Kazuyoshi Matsumura, Keita Fujikawa, Norimoto Gotoh, Takanobu Tsutsumi, Masakazu Shimizu, Kazuya Setoh, Meiko Takahashi, Yasuharu Tabara, Jun Mimura, Takefumi Nakamura, Toshiyuki Kimura, Chiharu Kawanami
Journal: The Lancet Rheumatology (2019)
Trends in Adherence to the <i>Physical Activity Guidelines for Americans</i> for Aerobic Activity and Time Spent on Sedentary Behavior Among US Adults, 2007 to 2016
Authors: Yang Du, Buyun Liu, Yangbo Sun, Linda G. Snetselaar, Robert B. Wallace, Wei Bao
Journal: JAMA Network Open (2019)

The updated 2018 Physical Activity Guidelines for Americans (PAG) reaffirmed key recommendations regarding aerobic activity in the 2008 edition and recently introduced health risks of sedentary behaviors and their association with physical activity.
REINFORCE: A randomized trial of resistance training in patients with radically treated respiratory cancer.
Authors: Veerle F Surmont, Bihiyga Salhi, Christel Haenebalcke, Sylvia Perez Bogerd, Delphine M Nguyen Dang, Roos Colman, Vincent Ninane, Karim Y Vermaelen, Thomas Malfait, Georges Van Maele, Eric Derom, Jan P. Van Meerbeeck
Journal: Journal of Clinical Oncology (2013)

7541 Background: Limited evidence suggest that patients (pts) with respiratory cancer improve their post-radical treatment (PRT) exercise capacity (EC) and quality of life (QoL) by rehabilitation (REH). Whole body vibration (WBV) is proposed as an alternative to conventional resistance training (CRT). REINFORCE investigates the effect of 2 supervised resistance training programs on functional and maximal EC and QoL, measured by resp. 6 minutes walking distance (6MWD), Wmax and EORTC-QLQ-C30 physical functioning (PF). Methods: Consecutive pts with cI-IIIB (N)SCLC or cI-II mesothelioma were evaluated before (M1) and after (M2) completion of either surgery (S) +/- platin-based chemotherapy (PCT) and postop. radiotherapy (RT) or RT +/- PCT, and then randomized to usual care (UC) or 38 sessions of either CRT or WBV. After stratification for COPD, S, PCT and center, 6MWD (primary endpoint), Wmax and PF were measured at M1, M2 and after 12 weeks (w) of REH (M3). Minimal clinical important difference in 6MWD is 54 m, in Wmax 10 Watt and in PF +9 points. Mean changes are compared within and in-between the intention-to-treat intervention groups using linear regression models. Results: 70 pts were randomized with balanced M1-characteristics: UC 24; CRT 24; WBV 22; male 73%, median age 62 y(29-79); median BMI 25 kg/m²(16-42); COPD 40%; NSCLC 91%; stage I-II 60%. 48% had S and 6% RT as sole therapy, 46% a combination of S or RT with PCT and/or PORT; pneumectomy in 19%. A median of 28 CRT-sessions (10 – 36) and 23 WBV-sessions (0 – 37) were attended with a median M2-M3 interval of 14 w (9-30). M2-M3 change in 6MWD is 95 m (58-132) in CRT (p&lt;.0001), 37m (-1-76) in WBV (p =0.06), 1 m(-34-36) in UC and is significantly higher with CRT than with WBV (p value vs. UC 0.0006 and 0.16, resp.) and highest in CRT-pts without COPD (133 m (86-181), p&lt; 0.0001). M3 values did not significantly exceed M1 with either intervention. M2-M3 change in Wmax significantly improved with 15 Watt (6-24) in both CRT and WBV(p= 0.002). M2-M3 PF increased 6 points (-1–14) in CRT (p= 0.1) and 8 points (0–16) in WBV (p=0.04). Conclusions: In pts with respiratory cancer, PRT REH is recommended, with CRT significantly improving functional and maximal EC and WBV increasing maximal EC and PF. Clinical trial information: NCT00752700.
Influential Role of Macrophages in Hepcidin Regulation in Apo-Transferrin Treated β-Thalassemic Mice
Authors: Daniel Moskop, Shuming Sun, Maria Feola, Marc Ruiz Martinez, Huiyong Chen, Jing Liu, Nathan Brinkman, Robert E Fleming, Stefano Rivella, Yelena Ginzburg
Journal: Blood (2017)
ATTACHE: A phase III, multicenter, randomized comparison of chemotherapy given prior to and post surgical resection versus chemotherapy given post surgical resection for hepatic metastases from colorectal cancer.
Authors: Jonathan Fawcett, Katrin Marie Sjoquist, Rob Padbury, Christopher Christophi, Niall Christopher Tebbutt, Charles Henry Caldow Pilgrim, Val Gebski, Nicole Wong, Christine Aiken, David Goldstein
Journal: Journal of Clinical Oncology (2012)

TPS3643 Background: No randomized studies have directly compared the role of peri-operative to adjuvant chemotherapy for resectable liver metastases. Benefit from post operative compared to peri-operative treatment has been suggested in a recent retrospective study of 499 patients with resected colorectal liver metastases which showed improved survival with entirely post-operative chemotherapy. Given this data and that of the small randomised trials demonstrating improved surgical outcomes with adjuvant chemotherapy, the role of entirely post-operative chemotherapy as a means of improving outcomes while reducing the negative effects of pre-operative treatment needs to be examined. Methods: 200 patients randomized 1:1 to 6 months of treatment post-operatively or 3 months of treatment pre-operatively and 3 months post-operatively. Site investigators will nominate chemotherapy schedule (mFOLFOX6, XELOX or FOLFIRI when adjuvant oxaliplatin received previously) prior to randomisation. Primary endpoint: proportion of patients in each arm with surgical complications within 30 days. Secondary endpoints: proportion of patients completing planned chemotherapy, post operative mortality rate (in each group), tolerability and safety of treatment, response rate by RECIST V1.1 and CEA, time to progression, time to treatment failure, overall survival, QoL (EORTC QLQ-C30 and QLQ-LMC21). A planned prospective meta-analysis with MRC (UK) and NSABP C-11 trials will have sufficient power to examine the effect of schedule (peri- or post-operative) on progression free survival (PFS). Eligibility: Patients with histologically proven colorectal cancer with radiologically confirmed, resectable liver metastases without evidence of extra-hepatic disease are eligible. Patients with synchronous metastases who have undergone resection of the primary tumour are eligible but patients requiring combined resection of primary cancer and liver metastatic disease are excluded. Patients with involved hilar nodes or wound implant metastases will not be eligible. Trial Status: Study opened to accrual August 2011.