tbuckley/cabot-search huggingface dataset:
Exercise and Acute Cardiovascular Events
Authors: Paul D. Thompson, Barry A. Franklin, Gary J. Balady, Steven N. Blair, Domenico Corrado, N.A. Mark Estes, Janet E. Fulton, Neil F. Gordon, William L. Haskell, Mark S. Link, Barry J. Maron, Murray A. Mittleman, Antonio Pelliccia, Nanette K. Wenger, Stefan N. Willich, Fernando Costa
Journal: Circulation (2007)

Habitual physical activity reduces coronary heart disease events, but vigorous activity can also acutely and transiently increase the risk of sudden cardiac death and acute myocardial infarction in susceptible persons. This scientific statement discusses the potential cardiovascular complications of exercise, their pathological substrate, and their incidence and suggests strategies to reduce these complications. Exercise-associated acute cardiac events generally occur in individuals with structural cardiac disease. Hereditary or congenital cardiovascular abnormalities are predominantly responsible for cardiac events among young individuals, whereas atherosclerotic disease is primarily responsible for these events in adults. The absolute rate of exercise-related sudden cardiac death varies with the prevalence of disease in the study population. The incidence of both acute myocardial infarction and sudden death is greatest in the habitually least physically active individuals. No strategies have been adequately studied to evaluate their ability to reduce exercise-related acute cardiovascular events. Maintaining physical fitness through regular physical activity may help to reduce events because a disproportionate number of events occur in least physically active subjects performing unaccustomed physical activity. Other strategies, such as screening patients before participation in exercise, excluding high-risk patients from certain activities, promptly evaluating possible prodromal symptoms, training fitness personnel for emergencies, and encouraging patients to avoid high-risk activities, appear prudent but have not been systematically evaluated.
Tumor Regression Grading After Preoperative Chemoradiotherapy as a Prognostic Factor and Individual-Level Surrogate for Disease-Free Survival in Rectal Cancer
Authors: Emmanouil Fokas, Philipp Ströbel, Rainer Fietkau, Michael Ghadimi, Torsten Liersch, Gerhard G Grabenbauer, Arndt Hartmann, Marco Kaufmann, Rolf Sauer, Ullrich Graeven, Hans Hoffmanns, Hans-Rudolf Raab, Torsten Hothorn, Christian Wittekind, Claus Rödel
Journal: JNCI Journal of the National Cancer Institute (2017)

We investigated tumor regression grading (TRG) as a prognostic marker and individual-level surrogate for disease-free survival (DFS) in patients with rectal carcinoma treated within the Chirurgische Arbeitsgemeinschaft fur Onkologie/Arbeitsgemeinschaft Radiologische Onkologie/Arbeitsgemeinschaft Internistische Onkologie (CAO/ARO/AIO)-04 randomized trial.TRG was recorded prospectively using the Dworak classification in 1179 patients after preoperative fluorouracil-based chemoradiotherapy (CRT) with or without oxaliplatin. Multivariable analysis was performed using Cox regression models adjusted for treatment arm, resection status, and pathologic stage. Individual-level surrogacy of TRG for DFS was examined using the four Prentice criteria (PC1-4). All statistical tests were two-sided.With a median follow-up of 50 months, the addition of oxaliplatin to fluorouracil-based CRT led to statistically significantly improved three-year DFS (75.9%, 95% CI = 72.3 to 79.5, vs 71.3%, 95% CI = 67.6 to 74.9, P = .04, PC 1) and a shift toward more advanced TRG groups ( P < .001, PC 2) compared with CRT with fluorouracil alone. The three-year DFS was 64.6% (95% CI = 57.3 to 71.9), 77.6% (95% CI = 74.5 to 80.7), and 92.3% (95% CI = 88.4 to 96.2) for TRG 0 + 1 (poor regression), TRG 2 + 3 (intermediate regression), and TRG 4 (complete regression), respectively ( P < .001, PC 3). TRG constituted an independent prognostic factor for DFS (TRG 2 + 3 vs TRG 0 + 1, HR = 0.68, 95% CI = 0.51 to 0.90, P = .007). Due to multicollinearity, TRG 4 and pathologic stage could not be tested within the same model. The treatment effect on DFS was captured by TRG, satisfying individual-level PC4.Higher TRG after preoperative CRT predicted a favorable long-term outcome. At the individual patient level, TRG was a surrogate marker for DFS. Further phase III trials are needed to validate TRG as a surrogate at trial level.
Infection related late mortality in survivors of childhood cancer with asplenia or radiation-induced hyposplenism: A report from the Childhood Cancer Survivor Study.
Authors: Brent Weil, Arin L Madenci, Qi Liu, Todd M. Gibson, Yutaka Yasui, Joseph Philip Neglia, Wendy M. Leisenring, Rebecca M. Howell, Emily S. Tonorezos, Danielle Novetsky Friedman, Christopher Tinkle, Lisa Diller, Gregory T. Armstrong, Kevin C. Oeffinger, Christopher Bertero Weldon
Journal: Journal of Clinical Oncology (2017)

10563 Background: Asplenia or hyposplenism can develop in survivors of childhood cancer following splenectomy or radiotherapy exposure to the left upper quadrant of the abdomen (LUQ). Knowledge regarding long-term infection related outcomes for these survivors is limited. Methods: Infection related late mortality (sepsis, meningitis or pneumonia) was evaluated in 20,805 5-year survivors (diagnosed &lt;21 years of age from 1970-1999, median follow-up 26 years, range 5-44) using cumulative incidence and Poisson regression models to calculate adjusted relative risk (RR) and 95% confidence intervals (CI). Average LUQ radiation was calculated as a surrogate for splenic radiation. Results: Treatment included splenectomy for 1328 survivors (6%). An additional 10,295 (49%) were exposed to LUQ radiotherapy without splenectomy. The cumulative incidence of infection related late mortality was 1.4% (95%CI: 0.7%-2.2%) at 35 years after splenectomy and 0.6% (95%CI: 0.4%-0.8%) after LUQ radiotherapy, with a total of 78 deaths attributable to infectious causes (25 sepsis, 1 meningitis, 52 pneumonia). Splenectomy (RR=8.4, p&lt;0.001) and increasing LUQ radiotherapy dose (p&lt;0.001) were independently associated with infection related late mortality (Table). Conclusions: Splenectomy and LUQ radiotherapy increased risk for infection related late mortality. While infectious mortality increased with increasing LUQ radiation dose, even lower dose exposure (&lt;10Gy) increased risk substantially. Accordingly, cancer survivors exposed to LUQ radiotherapy should be considered at risk for functional asplenia and managed similarly to asplenic individuals with respect to vaccinations and febrile illnesses. [Table: see text]
Association of a Family History of Atrial Fibrillation With Incidence and Outcomes of Atrial Fibrillation
Authors: Shang-Hung Chang, Chang-Fu Kuo, I-Jun Chou, Lai-Chu See, Kuang-Hui Yu, Shue-Fen Luo, Lu-Hsiang Huang, Weiya Zhang, Michael Doherty, Ming-Shien Wen, Chi-Tai Kuo, Yung-Hsin Yeh
Journal: JAMA Cardiology (2017)

<h3>Importance</h3> The heritability of atrial fibrillation (AF), the contribution of genetic and environmental factors, and the association of a family history of AF with prognosis are unclear. <h3>Objectives</h3> To measure genetic and environmental factors in the familial aggregation of AF and to estimate the association of a family history of AF with major adverse cardiovascular events (MACE). <h3>Design, Setting, and Participants</h3> In this Taiwanese nationwide population-based study among more than 23 million people, a custom data set was obtained using the data of all patients having a diagnosis of AF recorded between January 1996 and December 2013 in the Taiwan National Health Insurance Research Database. The study population comprised all 23 422 955 individuals registered with the database in 2013, of whom 177 770 had a diagnosis of AF and were included in the heritability estimation. From the latter, a subgroup of patients having newly diagnosed AF with a first-degree relative affected by AF between 2000 and 2010 were selected and matched 1:4 to controls without a family history for estimating MACE-free survival. The dates of analysis were January 2010 to December 2013. <h3>Main Outcomes and Measures</h3> The prevalence and relative risk of AF in relatives of patients with AF, as well as the relative contributions of heritability and shared and nonshared environmental factors to AF susceptibility. Also measured was MACE-free survival after AF was diagnosed. <h3>Results</h3> In total, 1510 patients (204 [13.5%] female; mean [SD] age, 57.9 [9.2] years) had newly diagnosed AF with a first-degree relative affected by AF. Individuals with a first-degree relative affected by AF had a relative risk of 1.92 (95% CI, 1.84-1.99) for AF. The accountability for the phenotypic variance of AF was 19.9% for genetic factors (heritability), 3.5% for shared environmental factors, and 76.6% for nonshared environmental factors. After matching for age, sex, hypertension, type 2 diabetes, previous stroke, and anticoagulation, incident AF patients with vs without an affected first-degree relative had similar MACE-free survival. <h3>Conclusions and Relevance</h3> Genetic and environmental factors were associated with AF, with nonshared environmental factors accounting for three-fourths of the phenotypic variance in Taiwan. Patients having AF with a first-degree relative affected by AF did not have more MACE. Therefore, family history may not be particularly informative in the diagnosis or management of AF.
EGFR and KRAS mutational status in Greek NSCLC patients using Sanger sequencing, High Resolution Melting curve analysis and next generation sequencing.
Authors: Eirini Papadopoulou, Nikolaos Tsoulos, Vasiliki Metaxa-Mariatou, Angeliki Tsirigoti, Angela Apessos, Konstantinos Agiannitopoulos, Kostas Zarogoulidis, Paul Zarogoulidis, Dimitrios Kasarakis, Stylianos Kakolyris, Jubrail Dahabreh, Fotis Vlastos, Charalampos Zoublios, Aggeliki Rapti, Niki Georgatou-Papageorgiou, Gerasimos Aravantinos, Vasilios Karavasilis, George Nasioulas
Journal: Journal of Clinical Oncology (2015)

e22178 Background: NSCLC patients harboring activating somatic mutations within the tyrosine kinase (TK) domain of the epidermal growth factor receptor (EGFR) significantly benefit from EGFR targeted therapy; therefore screening for EGFR has entered routine clinical practice. Several clinico-pathological factors correlate with EGFR and KRAS mutations including gender, smoking history, and histology. The frequency of EGFR mutations is also ethnicity-dependent, wherein the incidence in Caucasians is ~ 15%. However, limited data is available on intra-ethnic differences throughout Europe. Methods: High Resolution Melting Analysis (HRM) assay followed by Sanger sequencing was used to identify mutations in exons 18-21 of the EGFR gene and in exon 2 of the KRAS gene. A sensitive Targeted Next Generation Sequencing assay was also validated and used to correctly classify samples with equivocal results. Results: In total 233 of the 1472 (15.83%) Greek patients were found with a mutation in exons 18-21 of the EGFR gene. There was a 99,8% concordance between the HRM method and sequencing. NGS was revealed to be the most sensitive method (sensitivity 2-5% of mutant allele content depending on the mutation analyzed), however, it requires DNA of very good quality and quantity ( > 10ng/μL). Women non-smokers presented high prevalence of EGFR mutations. A KRAS exon 2 mutation was observed in 18.89% (106/561) of all tumors analyzed. Additionally, KRAS mutation analysis in patients with known smoking history revealed no difference in mutation frequency according to smoking status but a different mutation spectrum with prevalence of transversion mutations in former and ever smokers. Conclusions: Applying sensitive mutation detection techniques in a large cohort of unselected Greek NSCLC patients in routine diagnostic practice, we obtained an overall EGFR mutation frequency of 15.8%. This mutation frequency is comparable to that found in other European populations. Differences in sensitivity between techniques suggest that more than one technique should be advised in routine diagnostic practice.
Major Limitations in Using Element Concentrations in Hair as Biomarkers of Exposure to Toxic and Essential Trace Elements in Children
Authors: Helena Skröder, Maria Kippler, Barbro Nermell, Fahmida Tofail, Michael Levi, Syed Moshfiqur Rahman, Rubhana Raqib, Marie Vahter
Journal: Environmental Health Perspectives (2017)

Hair is a commonly used exposure biomarker for metals and other trace elements, but concern has been raised regarding its appropriateness for assessing the internal dose.The aim of the present study was to evaluate children's hair as biomarker of internal dose for toxic (As, Mn, Cd, Pb) and essential elements (Mg, Ca, Fe, Co, Cu, Zn, Se, Mo).In 207 children (9-10 years of age), originating from a population-based cohort in rural Bangladesh, we measured concentrations of the selected elements in hair ( closest to the scalp) using ICP-MS. We compared these with previously measured concentrations in erythrocytes, urine, and water. For a subset of children (n=19), we analyzed four consecutive 2 cm pieces of hair.There were strong associations between hair As and the other biomarkers (erythrocytes: rs=0.73, p<0.001; urine: rS=0.66, p<0.001); and water (rs=0.60, p<0.001); and there were significant correlations between Se in hair and erythrocytes (overall rs=0.38, p<0.001), and urine (rs=0.29, p<0.001). Hair Co and Mo showed weak correlations with concentrations in erythrocytes. Hair Mn was not associated with Mn in erythrocytes, urine, or water, and the geometric mean concentration increased almost five times from the 2 cm closest to the head to the 7th–8th cm (p<0.001). Also Mg, Ca, Co, Cd, and Pb increased from the scalp outward (>50% higher in 7th–8th cm compared with 1st–2nd cm, p<0.001).Hair was found to be a useful exposure biomarker of absorbed As and Se only. Of all measured elements, hair Mn seemed the least reflective of internal dose. https://doi.org/10.1289/EHP1239.
Launch of new series: bright spots, physical activity investments that work
Authors: Emmanuel Stamatakis, Andrew Murray
Journal: British Journal of Sports Medicine (2017)

The technological, economical and labour trends that practically eliminated the need for daily physical activity in much of the developed and increasingly in the developing world occurred far too rapidly for human physiology to efficiently adapt. The result is the escalating epidemic of chronic diseases that are contributed to or amplified by physical inactivity. Re-engineering the world to help us prioritise physical activity presents many challenges. There is no single solution or ‘silver bullet’. Understanding a complex problem like physical inactivity requires interdisciplinary thinking and appreciation of both the local and global context. What is clear is that tackling physical inactivity requires a multisectoral response that goes well beyond the traditional healthcare settings and involves, for example, government entities, non-governmental organisations, and private industry. Launched in 2012, the Investments that Work for Physical Activity initiative,1 builds on the 2010 Toronto Charter for Physical Activity …
Abstract P322: Chamber-Specific Differences in Oxidative Stress in Newborn Versus Adult Rabbit Hearts Following Ischemia-Reperfusion
Authors: E Bernadette Cabigas, Guoliang Ding, Tao Chen, Talib Saafir, Mary B Wagner, Michael E Davis
Journal: Circulation Research (2011)

Each year, tens of thousands of children undergo cardiopulmonary bypass (CPB) to correct congenital heart defects. While necessary for surgery, CPB involves stopping the heart and exposing it to ischemic conditions. While much is known about adult injury, little is known about the effects of global ischemia on newborn ventricles. The purpose of this study was to determine age- and chamber-specific differences in oxidative stress following global ischemia-reperfusion injury. We studied newborn (2–4 days) and adult (&gt;8 weeks) rabbit hearts subjected to Langendorff ischemia-reperfusion (30 minutes ischemia, 60 minutes reperfusion). Catalase and superoxide dismutase (SOD) activities were measured, as well as real-time hydrogen peroxide (H 2 O 2 ) and superoxide (O 2 − ) generation using confocal microscopy in isolated left and right ventricular (LV and RV) myocytes exposed to hypoxia. Our data demonstrate chamber and age-specific changes in oxidative stress. During ischemia, H 2 O 2 increased significantly in the RV while remaining constant in the LV of newborn rat rabbit myocytes. In contrast, there was a smaller, nonsignificant increase in H 2 O 2 in both both RV and LV myocytes of adults. The increase seen in the RV of newborns was several fold higher than that of adults (4.3-fold vs. 2.2 fold; p&lt;0.05). In whole heart tissue, catalase activity was significantly increased following ischemia in both adult ventricles, while no increase was seen in newborn hearts compared to sham hearts. Additionally, levels in newborns were several fold lower (p&lt;0.05), indicating less scavenging potential. SOD activity was increased from sham vs. ischemia in the LV of both adult and newborn hearts, but only in the RV of the newborn heart (0.80±0.09 to 3.0±0.43 U/mg; p&lt;0.001). Intra-cardiac injection of an H 2 O 2 scavenger, Ebselen, loaded in nanoparticles, improved recovery of developed pressure (49.53±16.25 to 80.0±11.31) in the RV of the newborn (p&lt;0.05), suggesting the local delivery of an exogenous antioxidant is cardioprotective in newborn RVs. Our data demonstrate there are ventricle-specific differences in oxidative stress between newborn and adult rabbit hearts. Local therapy is able to address some of these differences and may limit damage during bypass surgery.
FOLFOX4/XELOX in stage II–III colon cancer: Early survival data of the Italian three or six colon adjuvant (TOSCA) trial
Authors: Roberto Labianca, Claudia Mucciarini, Paolo Bidoli, Domenico Corsi, Vincenzo Montesarchio, Maria Bochicchio Anna, Vincenzo Iaffaioli, Andrea Ciarlo, Sabino De Placido, Domenico Amoroso, Enrico Cortesi, Bruno Daniele, Dino Amadori, Daniele Turci, Silvia Pelliccioni, Saverio Cinieri, Alberto Ravaioli, Elena Piazza, Eliana Rulli, Alberto Sobrero
Journal: Annals of Oncology (2017)
Prognostic impact of primary tumor location in metastatic colorectal cancer (mCRC). A 5 year retrospective analysis of our treated population.
Authors: Gonçalo Atalaia, Marta Vaz Baptista, Tiago Tomás, Susana Almeida, Inês Eiriz, Nuno Guerra, Sofia Braga, Ana Del Rio, Teresa Fuiza
Journal: Annals of Oncology (2017)
Activity of brigatinib (BRG) in crizotinib (CRZ) resistant patients (pts) according to ALK mutation status.
Authors: Scott N. Gettinger, Sen Zhang, J. Graeme Hodgson, Lyudmila Bazhenova, Sjaak Burgers, Dong-Wan Kim, Daniel Shao-Weng Tan, Han A. Koh, James C. M. Ho, Santiago Viteri Ramirez, Alice Tsang Shaw, Glen J. Weiss, Corey J. Langer, Rudolf M. Huber, Myung-Ju Ahn, William G Reichmann, David Kerstein, Victor M. Rivera, D. Ross Camidge
Journal: Journal of Clinical Oncology (2016)

9060 Background: BRG is an investigational, selective ALK inhibitor with potent preclinical activity against native ALK and a broad set of mutants associated with clinical resistance to CRZ. BRG has shown promising efficacy in ALK rearranged (+) NSCLC pts previously treated with CRZ in a phase (Ph) 1/2 trial. We examined the association between BRG efficacy and ALK mutation status using tumor specimens collected after CRZ and prior to BRG treatment (tx) (baseline [BL]), and after BRG tx (Post-BL) in pts enrolled in the Ph1/2 trial and a Ph2 trial of ALK+ NSCLC pts whose disease progressed on CRZ (ALTA). Methods: Samples analysis: FoundationOne next-generation sequencing (NGS) platform. BRG activity: best response (RECIST v1.1) from BL. Data reported: Jan, 2016 for sample analyses, Nov and Dec, 2015 for Ph1/2 and ALTA clinical results, respectively. Results: Of the 301 ALK+ NSCLC pts enrolled in the Ph1/2 (N = 79) and ALTA (N = 222) trials, evaluable tumor samples were obtained from 30 pts at BL. Confirmed overall response in these pts was 63% (19/30). Secondary ALK mutations were detected in 30% (9/30) of pts. Confirmed ORR in these pts was 67% (6/9); 6 confirmed partial responses (PRs) (3 F1174L, L1196M, S1206F, and G1269A); 1 PR (G1202R) awaiting confirmation; 1 stable disease (SD) (L1196M) in a pt with 1 cycle (C = 28 days) of tx; 1 progressive disease (PD) (F1245V). Secondary ALK mutations were not detected in 70% (21/30) of pts, including 4 who were ALK fusion (-) by NGS (but ALK+ locally). Confirmed ORR in these pts was 62% (13/21); 2 CR, 11 PR, 7 SD, and 1 PD; including 3 SD and 1 PD in ALK (-) pts. Post-BL samples were collected from 5 pts (all Ph1/2), 2 of whom also had BL samples. Secondary ALK mutations, and other genetic aberrations of interest, were detected in 4 pts: 1 with F1174L (at C13 [also present at BL]; PD at C13); 2 with G1202R (at C21 [not present at BL]; PD at C13; and at C35 [BRAF G469A also detected]; PD at C35); and 1 with D1203N, G1269A, and I1171H (at C9; PD at C7). Conclusions: BRG maintains activity in CRZ resistant ALK+ NSCLC independent of the presence of secondary ALK mutations. While 2 single mutants (F1174L and G1202R) have been detected after long term tx with BRG, responses were also observed when these mutants were present at BL. Clinical trial information: NCT01449461 and NCT02094573.
Nitroglycerine and Angina
Authors: K. Lance Gould, Nils P. Johnson
Journal: Circulation (2017)

Article, see p 24 N itroglycerin (NTG) was invented in 1847 and used for angina pectoris or heart failure since 1879 as reviewed by Asrress et al 1 in the current issue of Circulation.An extensive literature shows that NTG lowers blood pressure, vasodilates epicardial coronary arteries, and in experimental models increases coronary blood flow to the subendocardium. Nitroglycerine and Angina
Outcome of Endoscopic Balloon Dilatation of Anastomotic Strictures in Crohn's Disease
Authors: G Doherty, D Keegan, D O'Donoghue, H Mulcahy
Journal: Endoscopy (2006)

Aims: Anastomotic stricture formation is a common indication for further resection in patients with Crohn's disease (CD). We evaluated outcomes following endoscopic balloon dilatation of symptomatic anastomotic strictures.
Endoscopic Ultrasound Guided Fine Needle Aspiration Biopsy (EUS FNAB) in the Diagnosis of Gastrointestinal and Mediastinal Disease
Authors: SO Riordan, E Clarke, F Gleeson, S Sengupta, N Mulligan, J Lennon, P MacMathuna
Journal: Endoscopy (2006)

Aims: Management of GI malignancy is determined by accurate staging (TNM) using CT, MRI and PET. These modalities have limitations with regard to tumour stage, local extension and the differentiation of benign and malignant adenopathy, which may be overcome by EUS / EUS FNAB. To assess the technical success, the diagnostic yield and complications of EUS FNAB.