bluuebunny/crossref_metadata_2025_split huggingface dataset:
Changes to the cardiac biomarkers of non-elite athletes completing the 2009 London Marathon
Authors: Baker Polly , Davies Sarah Louise , Larkin Joanne , Moult Daniel , Benton Sally , Roberts Andrew , Harris Timothy 
Published: March 2013

IntroductionMany studies have demonstrated a rise in troponin and brain natriuretic peptide (BNP) levels following prolonged and/or strenuous exercise. Only one study looked at athletes who collapse and this showed no difference in cardiac biomarkers between those who collapsed and those who completed without requiring medical attention. We set out to describe and quantify the changes in troponin and BNP in three groups of non-elite runners at the 2009 London marathon: those with and without known structural heart disease (SHD) and those who collapsed on completion.MethodsThe first group (recruited group, RG) was recruited at the prerace exhibition. This group had two subsets, runners with SHD and without (non-SHD). A second group was recruited from those who collapsed (collapsed group, CG). Blood was taken for troponin I (TnI), troponin T (TnT), high sensitivity TnT (HSTnT) and BNP.ResultsCardiac biomarker levels increased in all groups following the marathon. No statistically significant difference was seen between the SHD and non-SHD subgroups. When comparing the RG and CG the number and degree of rise was greater in those who collapsed. A trend for the degree of rise of HSTnT was demonstrated.DiscussionWe identified runners with troponin levels that, in other circumstances, would raise concern for myocardial necrosis. However absence of adverse clinical sequelae would suggest this rise is physiological. The cause and clinical significance of the increased HSTnT levels seen in those that collapsed is yet to be fully elucidated.
Risk Factors for Second Screen-Detected or Interval Breast Cancers in Women with a Personal History of Breast Cancer Participating in Mammography Screening
Authors: Houssami Nehmat , Abraham Linn A. , Kerlikowske Karla , Buist Diana S.M. , Irwig Les , Lee Janie , Miglioretti Diana L. 
Published: March 2013

Abstract
Background: Women with a personal history of breast cancer (PHBC) have increased risk of an interval cancer. We aimed to identify risk factors for second (ipsilateral or contralateral) screen-detected or interval breast cancer within 1 year of screening in PHBC women.
Methods: Screening mammograms from women with history of early-stage breast cancer at Breast Cancer Surveillance Consortium-affiliated facilities (1996–2008) were examined. Associations between woman-level, screen-level, and first cancer variables and the probability of a second breast cancer were modeled using multinomial logistic regression for three outcomes [screen-detected invasive breast cancer, interval invasive breast cancer, or ductal carcinoma in situ (DCIS)] relative to no second breast cancer.
Results: There were 697 second breast cancers, of these 240 were interval cancers, among 67,819 screens in 20,941 women. In separate models for women with DCIS or invasive first cancer, first breast cancer surgery predicted all three second breast cancer outcomes (P &lt; 0.001), and high ORs for second breast cancers (between 1.95 and 4.82) were estimated for breast conservation without radiation (relative to mastectomy). In women with invasive first breast cancer, additional variables predicted risk (P &lt; 0.05) for at least one of the three outcomes: first-degree family history, dense breasts, longer time between mammograms, young age at first breast cancer, first breast cancer stage, and adjuvant systemic therapy for first breast cancer; and risk of interval invasive breast cancer was highest in women &lt;40 years at first breast cancer (OR, 3.41; 1.34–8.70), those with extremely dense breasts (OR, 2.55; 1.4–4.67), and those treated with breast conservation without radiation (OR, 2.67; 1.53–4.65).
Conclusion: Although the risk of a second breast cancer is modest, our models identify risk factors for interval second breast cancer in PHBC women.
Impact: Our findings may guide discussion and evaluations of tailored breast screening in PHBC women, and incorporating this information into clinical decision-making warrants further research. Cancer Epidemiol Biomarkers Prev; 22(5); 946–61. ©2013 AACR.
A Prospective Study of Leukocyte Telomere Length and Risk of Renal Cell Carcinoma
Authors: Hofmann Jonathan N. , Lan Qing , Cawthon Richard , Hosgood H. Dean , Shuch Brian , Moore Lee E. , Rothman Nathaniel , Chow Wong-Ho , Purdue Mark P. 
Published: March 2013

Abstract
Background: It has been hypothesized that genomic instability related to telomere dysfunction may contribute to carcinogenesis. There is some evidence from case–control studies suggesting that short leukocyte telomere length may be associated with an increased risk of renal cell carcinoma (RCC); however, this association has not been investigated prospectively.
Methods: We conducted a nested case–control study (209 cases, 410 controls) of RCC risk in relation to prediagnostic leukocyte telomere length in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. ORs and 95% confidence intervals (CI) were estimated using conditional logistic regression.
Results: Leukocyte telomere length was not significantly associated with future risk of RCC (highest quartile vs. lowest: OR, 0.8; 95% CI, 0.5–1.5; Ptrend = 0.6). Analyses stratified by sex, age, and time from blood collection to RCC diagnosis were similarly null.
Conclusions: The results of this study, to our knowledge the first prospective investigation of its kind, do not support an association between prediagnostic leukocyte telomere length and risk of RCC.
Impact: In contrast to some earlier reports, our findings add to the evidence that leukocyte telomere length is not a biomarker of risk related to the etiology of RCC. Cancer Epidemiol Biomarkers Prev; 22(5); 997–1000. ©2013 AACR.
RAD51C-Deficient Cancer Cells Are Highly Sensitive to the PARP Inhibitor Olaparib
Authors: Min Ahrum , Im Seock-Ah , Yoon Young-Kwang , Song Sang-Hyun , Nam Hyun-Jin , Hur Hyung-Seok , Kim Hwang-Phill , Lee Kyung-Hun , Han Sae-Won , Oh Do-Youn , Kim Tae-You , O'Connor Mark J. , Kim Woo-Ho , Bang Yung-Jue 
Published: March 2013

Abstract
A PARP inhibitor is a rationally designed targeted therapy for cancers with impaired DNA repair abilities. RAD51C is a paralog of RAD51 that has an important role in the DNA damage response. We found that cell lines sensitive to a novel oral PARP inhibitor, olaparib, had low levels of RAD51C expression using microarray analysis, and we therefore hypothesized that low expression of RAD51C may hamper the DNA repair process, resulting in increased sensitivity to olaparib. Compared with the cells with normal RAD51C expression levels, RAD51C-deficient cancer cells were more sensitive to olaparib, and a higher proportion underwent cell death by inducing G2–M cell-cycle arrest and apoptosis. The restoration of RAD51C in a sensitive cell line caused attenuation of olaparib sensitivity. In contrast, silencing of RAD51C in a resistant cell line enhanced the sensitivity to olaparib, and the number of RAD51 foci decreased with ablated RAD51C expression. We also found the expression of RAD51C was downregulated in cancer cells due to epigenetic changes and RAD51C expression was low in some gastric cancer tissues. Furthermore, olaparib significantly suppressed RAD51C-deficient tumor growth in a xenograft model. In summary, RAD51C-deficient cancer cells are highly sensitive to olaparib and offer preclinical proof-of-principle that RAD51C deficiency may be considered a biomarker for predicting the antitumor effects of olaparib. Mol Cancer Ther; 12(6); 865–77. ©2013 AACR.
Lipid Metabolism Genes in Contralateral Unaffected Breast and Estrogen Receptor Status of Breast Cancer
Authors: Wang Jun , Scholtens Denise , Holko Michelle , Ivancic David , Lee Oukseub , Hu Hong , Chatterton Robert T. , Sullivan Megan E. , Hansen Nora , Bethke Kevin , Zalles Carola M. , Khan Seema A. 
Published: March 2013

AbstractRisk biomarkers that are specific to estrogen receptor (ER) subtypes of breast cancer would aid the development and implementation of distinct prevention strategies. The contralateral unaffected breast of women with unilateral breast cancer (cases) is a good model for defining subtype-specific risk because women with ER-negative (ER−) index primaries are at high risk for subsequent ER-negative primary cancers. We conducted random fine needle aspiration of the unaffected breasts of cases. Samples from 30 subjects [15 ER-positive (ER+) and 15 ER− cases matched for age, race and menopausal status] were used for Illumina expression array analysis. Findings were confirmed using quantitative real-time PCR (qRT-PCR) in the same samples. A validation set consisting of 36 subjects (12 ER+, 12 ER− and 12 standard-risk healthy controls) was used to compare gene expression across groups. ER− case samples displayed significantly higher expression of 18 genes/transcripts, 8 of which were associated with lipid metabolism on gene ontology analysis (GO: 0006629). This pattern was confirmed by qRT-PCR in the same samples, and in the 24 cases of the validation set. When compared to the healthy controls in the validation set, significant overexpression of 4 genes (DHRS2, HMGCS2, HPGD and ACSL3) was observed in ER− cases, with significantly lower expression of UGT2B11 and APOD in ER+ cases, and decreased expression of UGT2B7 in both subtypes. These data suggest that differential expression of lipid metabolism genes may be involved in the risk for subtypes of breast cancer, and are potential biomarkers of ER-specific breast cancer risk. Cancer Prev Res; 6(4); 321–30. ©2013 AACR.
A Stepwise Approach to the Management of Postinfarct Ventricular Tachycardia Using Catheter Ablation as the First-Line Treatment
Authors: Pauriah Maheshwar , Cismaru Gabriel , Magnin-Poull Isabelle , Andronache Marius , Sellal Jean-Marc , Schwartz Jérôme , Brembilla-Perrot Béatrice , Sadoul Nicolas , Aliot Etienne , de Chillou Christian 
Published: March 2013

Background—
The occurrence of ventricular tachycardia (VT) after myocardial infarction is associated with poorer prognosis. In such patients, implantable cardioverter-defibrillators are recommended. Catheter ablation of VT is currently recommended only as an adjunctive therapy. Whether a successful VT ablation alone might be a viable strategy in some of these patients, however, remains unknown. The aim of the present study was to evaluate this strategy.

Methods and Results—

Between January 2002 and December 2011, 189 patients with cardiomyopathy underwent 259 VT ablations in our center. Forty-five patients (mean age, 65.2±9.6 years; 91% men) with a history of myocardial infarction and mean left ventricular ejection fraction of 39.7±9.7% matched the study criteria and were included in this analysis. Acute success was obtained in 40 of 45 patients (88.9%). During a follow-up, on the basis of our stepwise algorithm (using acute success, repeat electrophysiological study, and recurrence of VT), 19 of 45 patients (42.2%) underwent implantable cardioverter-defibrillators implantation. During a median follow-up of 4.5 (interquartile range, 2.1–7.0) years, all-cause mortality occurred in 14 of 45 patients (31.1%). Using multivariate Cox regression analysis, age (hazard ratio, 1.13; 95% confidence interval, 1.03–1.22;
P
=0.007) was the only independent predictor of mortality, whereas implantable cardioverter-defibrillators implantation was not (hazard ratio, 0.54; 95% confidence interval, 0.18–1.64;
P
=0.28)

Conclusions—
Our results suggest that a stepwise approach to the management of VT with ablation as a first-line treatment in postinfarct patients presenting with VT might be a reasonable option. Further studies are required to confirm these results.
Outcome Differences in Community- Versus Hospital-Acquired Hyponatremia in Patients With a Diagnosis of Heart Failure
Authors: Shchekochikhin Dmitry Y. , Schrier Robert W. , Lindenfeld JoAnn , Price Lori Lyn , Jaber Bertrand L. , Madias Nicolaos E. 
Published: March 2013

Background—
Hyponatremia at hospital admission is a well-known risk factor of morbidity and mortality in patients with heart failure (HF). However, there are few data about hyponatremia developing during hospitalization in patients with HF. The present study compares hospital-acquired hyponatremia (HAH) with community-acquired hyponatremia (CAH) in HF patients with respect to outcome.

Methods and Results—
A total of 5347 consecutive hospitalized patients with a diagnosis of HF were analyzed. CAH was defined as a serum sodium value of ≤135 mEq/L at the time of hospital admission. HAH was defined as development of a serum sodium level of ≤135 mEq/L during hospitalization in the setting of a serum sodium value >135 mEq/L on admission. In-hospital mortality, length of stay, worsening kidney function, and discharge to short-/long-term care facilities were analyzed. CAH and HAH were identified in 1039 patients (19.4%) and in 1302 patients (24.4%) of the 5347 patients admitted, respectively. Both types of hyponatremia were associated with increased mortality, length of stay, rate of discharge to short-/long-term care facilities, and worsening kidney function. In-hospital mortality did not differ between CAH and HAH, but differences in demographics and comorbidities were present.

Conclusions—
The present results identified HAH as a risk factor for increased mortality in HF as has been previously described for CAH. HAH was associated with increased length of stay, discharge to short-/long-term care facilities, and development of cardio-renal failure. Thus, hyponatremia in hospitalized patients with a diagnosis of HF, either on admission or during hospitalization, is a prognostic marker for poor outcomes.
Perioperative Dexmedetomidine Improves Outcomes of Cardiac Surgery
Authors: Ji Fuhai , Li Zhongmin , Nguyen Hung , Young Nilas , Shi Pengcai , Fleming Neal , Liu Hong 
Published: March 2013

Background—
Cardiac surgery is associated with a high risk of cardiovascular and other complications that translate into increased mortality and healthcare costs. This retrospective study was designed to determine whether the perioperative use of dexmedetomidine could reduce the incidence of complications and mortality after cardiac surgery.

Methods and Results—

A total of 1134 patients who underwent coronary artery bypass surgery and coronary artery bypass surgery plus valvular or other procedures were included. Of them, 568 received intravenous dexmedetomidine infusion and 566 did not. Data were adjusted with propensity scores, and multivariate logistic regression was used. The primary outcomes measured included mortality and postoperative major adverse cardiocerebral events (stroke, coma, perioperative myocardial infarction, heart block, or cardiac arrest). Secondary outcomes included renal failure, sepsis, delirium, postoperative ventilation hours, length of hospital stay, and 30-day readmission. Dexmedetomidine use significantly reduced postoperative in-hospital (1.23% versus 4.59%; adjusted odds ratio, 0.34; 95% confidence interval, 0.192–0.614;
P
<0.0001), 30-day (1.76% versus 5.12%; adjusted odds ratio, 0.39; 95% confidence interval, 0.226–0.655;
P
<0.0001), and 1-year (3.17% versus 7.95%; adjusted odds ratio, 0.47; 95% confidence interval, 0.312–0.701;
P
=0.0002) mortality. Perioperative dexmedetomidine therapy also reduced the risk of overall complications (47.18% versus 54.06%; adjusted odds ratio, 0.80; 95% confidence interval, 0.68–0.96;
P
=0.0136) and delirium (5.46% versus 7.42%; adjusted odds ratio, 0.53; 95% confidence interval, 0.37–0.75;
P
=0.0030).

Conclusion—
Perioperative dexmedetomidine use was associated with a decrease in postoperative mortality up to 1 year and decreased incidence of postoperative complications and delirium in patients undergoing cardiac surgery.

Clinical Trial Registration—

URL:
www.clinicaltrials.gov
. Unique identifier: NCT01683448.
Safety of Pacemaker Implantation in Nonagenarians
Authors: Mandawat Anant , Curtis Jeptha P. , Mandawat Aditya , Njike Valentine Y. , Lampert Rachel 
Published: March 2013

Background—
Data are scarce on outcomes of pacemaker implantation in nonagenarians (age≥90 years).

Methods and Results—

We identified patients >70 years of age (n=115 683) who underwent initial pacemaker implantation in the 2004 to 2008 Healthcare Cost and Utilization Project–Nationwide Inpatient Sample. Outcomes included in-hospital mortality, complications, length of stay, and charges. Unadjusted outcomes were compared using χ
2
and Mantel-Haenszel tests. Multivariate hierarchical logistic models and stepwise linear regression models adjusted for case-mix variation and clustering. Eleven percent (12 917) were >90 years of age. Relative to patients aged 70 to 79 years, patients >90 years of age were more likely to have moderate/severe comorbidity (Charlson score >1; 43.2% versus 40.1%) and less likely to be admitted electively (17.5% versus 29.9%), all
P
<0.001. The unadjusted mortality and complication rates in patients aged 70 to 79 years were 0.60% (confidence interval [CI], 0.53–0.67%) and 5.61% (CI, 5.40–5.82%), respectively, and in patients aged >90 years were 1.87% (CI, 1.63–2.11%) and 6.31% (CI, 5.89–6.72%). Length of stay and charges in patients aged 70 to 79 years were 3.22 days (CI, 3.20–3.24 days) and $38 871 (CI, $38 700–$39 043), and in patients aged >90 years, 4.27 days (CI, 4.25–4.30 days) and $41 373 (CI, $41 190–$41 556). Multivariable analysis revealed severe comorbidity (odds ratio, 5.00; 95% CI, 4.05–6.17) was a greater predictor of mortality than increasing age (odds ratio, 2.81 per decade; CI, 2.35–3.35), all
P
<0.001. Similarly, severe comorbidity (Charlson score >5) was more strongly associated with complications, length of stay, and charges than age.

Conclusions—
Although increasing age predicts worsening outcomes in the elderly, the absolute rates are modest, even in nonagenarians, and comorbidity is a stronger predictor.
Activation of Lung p53 by Nutlin-3a Prevents and Reverses Experimental Pulmonary Hypertension
Authors: Mouraret Nathalie , Marcos Elisabeth , Abid Shariq , Gary-Bobo Guillaume , Saker Mirna , Houssaini Amal , Dubois-Rande Jean-Luc , Boyer Laurent , Boczkowski Jorge , Derumeaux Geneviève , Amsellem Valérie , Adnot Serge 
Published: March 2013

Background—
Induction of cellular senescence through activation of the p53 tumor suppressor protein is a new option for treating proliferative disorders. Nutlins prevent the ubiquitin ligase MDM2 (murine double minute 2), a negative p53 regulator, from interacting with p53. We hypothesized that cell senescence induced by Nutlin-3a exerted therapeutic effects in pulmonary hypertension (PH) by limiting the proliferation of pulmonary artery smooth muscle cells (PA-SMCs).

Methods and Results—

Nutlin-3a treatment of cultured human PA-SMCs resulted in cell growth arrest with the induction of senescence but not apoptosis; increased phosphorylated p53 protein levels; and expression of p53 target genes including p21, Bax, BTG2, and MDM2. Daily intraperitoneal Nutlin-3a treatment for 3 weeks dose-dependently reduced PH, right ventricular hypertrophy, and distal pulmonary artery muscularization in mice exposed to chronic hypoxia or SU5416/hypoxia. Nutlin-3a treatment also partially reversed PH in chronically hypoxic or transgenic mice overexpressing the serotonin-transporter in SMCs (SM22-5HTT+ mice). In these mouse models of PH, Nutlin-3a markedly increased senescent p21-stained PA-SMCs; lung p53, p21, and MDM2 protein levels; and p21, Bax, PUMA, BTG2, and MDM2 mRNA levels; but induced only minor changes in control mice without PH. Marked MDM2 immunostaining was seen in both mouse and human remodeled pulmonary vessels, supporting the use of Nutlins as a PH-targeted therapy. PH prevention or reversal by Nutlin-3a required lung p53 stabilization and increased p21 expression, as indicated by the absence of Nutlin-3a effects in hypoxia-exposed p53
−/−
and p21
−/−
mice.

Conclusions—
Nutlin-3a may hold promise as a prosenescence treatment targeting PA-SMCs in PH.
Synergetic Neuroprotection of Normobaric Oxygenation and Ethanol in Ischemic Stroke Through Improved Oxidative Mechanism
Authors: Geng Xiaokun , Fu Paul , Ji Xunming , Peng Changya , Fredrickson Vance , Sy Christopher , Meng Ran , Ling Feng , Du Huishan , Tan Xiaomu , Hüttemann Maik , Guthikonda Murali , Ding Yuchuan 
Published: March 2013

Background and Purpose—
Normobaric oxygenation (NBO) and ethanol both provide neuroprotection in stroke. We evaluated the enhanced neuroprotective effect of combining these 2 treatments in a rat stroke model.

Methods—

Sprague-Dawley rats were subjected to middle cerebral artery occlusion for 2 hours. Reperfusion was then established and followed by treatment with either (1) an intraperitoneal injection of ethanol (1.0 g/kg), (2) NBO treatment (2-hour duration), or (3) NBO plus ethanol. The extent of brain injury was determined by infarct volume and motor performance. Oxidative metabolism was determined by ADP/ATP ratios, reactive oxygen species levels, nicotinamide adenine dinucleotide phosphate oxidase activity, and pyruvate dehydrogenase activity. Protein expression of major nicotinamide adenine dinucleotide phosphate oxidase subunits (p47
phox
, gp91
phox
, and p67
phox
) and the enzyme pyruvate dehydrogenase was evaluated through Western immunoblotting.

Results—
NBO and ethanol monotherapies each demonstrated reductions as compared to stroke without treatment in infarct volume (36.7% and 37.9% vs 48.4%) and neurological deficits (score of 6.4 and 6.5 vs 8.4); however, the greatest neuroprotection (18.8% of infarct volume and 4.4 neurological deficit) was found in animals treated with combination therapy. This neuroprotection was associated with the largest reductions in ADP/ATP ratios, reactive oxygen species levels, and nicotinamide adenine dinucleotide phosphate oxidase activity, and the largest increase in pyruvate dehydrogenase activity.

Conclusions—
Combination therapy with NBO and ethanol enhances the neuroprotective effect produced by each therapy alone. The mechanism behind this synergistic action is related to changes in cellular metabolism after ischemia reperfusion. NBO plus ethanol is attractive for clinical study because of its ease of use, tolerability, and tremendous neuroprotective potential in stroke.