bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rosuvastatin improves impaired endothelial function, lowers high sensitivity CRP, complement and immuncomplex production in patients with systemic sclerosis - a prospective case-series study
Authors: Timár Orsolya , Szekanecz Zoltán , Kerekes György , Végh Judit , Oláh Anna V , Nagy Gábor , Csiki Zoltán , Dankó Katalin , Szamosi Szilvia , Németh Ágnes , Soltész Pál , Szücs Gabriella 
Published: September 2013

Abstract
Introduction
We studied the effect of rosuvastatin on endothelial and macrovascular function, cardiovascular risk factors and the complement pathway in patients with systemic sclerosis (SSc).

Methods
Altogether 28 patients with SSc underwent laboratory and complex vascular assessments before and after six months of 20 mg rosuvastatin treatment. Flow-mediated dilation (FMD) of the brachial artery, as well as carotid artery intima-media thickness (ccIMT), carotid-femoral and aorto-femoral pulse wave-velocity (PWV) were analyzed by ECG-synchronized ultrasound. Ankle-brachial index (ABI) was determined by Doppler, and forearm skin microcirculation was assessed by Laser Doppler perfusion monitoring.

Results
Brachial artery FMD significantly improved upon rosuvastatin therapy (2.2% ± 3.3% before versus 5.7% ± 3.9% after treatment, P = 0.0002). With regard to patient subsets, FMD significantly improved in the 21 lcSSc patients (from 2.1% to 5.6%, P = 0.001). In the seven dcSSc patients, we observed a tendency of improvement in FMD (from 3% to 6%, P = 0.25). Changes in PWV, ccIMT and ABI were not significant. Mean triglyceride (1.7 ± 0.97 versus 1.3 ± 0.46 mmol/l, P = 0.0004), total cholesterol (5.3 ± 1.6 mmol/l versus 4.2 ± 1.3 mmol/l, P = 0.0003), low density lipoprotein cholesterol (3.0 ± 1.3 versus 2.2 ± 1.0 mmol/l, P = 0.005) and C-reactive protein levels (CRP) (5.1 ± 5.2 versus 3.4 ± 2.7, P = 0.01) levels significantly decreased after rosuvastatin treatment. Mean C3, C4 and IC levels also decreased significantly as compared to pretreatment values.

Conclusions
Six-month rosuvastatin therapy improves endothelial function and lowers CRP, C3, C4 and IC levels indicating possible favourable effects of this statin on the cardiovascular and immune system in SSc.
Cancer stem cell markers are enriched in normal tissue adjacent to triple negative breast cancer and inversely correlated with DNA repair deficiency
Authors: Atkinson Rachel L , Yang Wei T , Rosen Daniel G , Landis Melissa D , Wong Helen , Lewis Michael T , Creighton Chad J , Sexton Krystal R , Hilsenbeck Sue G , Sahin Aysegul A , Brewster Abenaa M , Woodward Wendy A , Chang Jenny C 
Published: September 2013

Abstract
Introduction
We hypothesized that cells present in normal tissue that bear cancer stem cell markers may represent a cancer cell of origin or a microenvironment primed for tumor development, and that their presence may correlate with the clinically defined subtypes of breast cancer that show increased tumorigenicity and stem cell features.

Methods
Normal tissues sampled at least 5 cm from primary tumors (normal adjacent tissue) were obtained from 61 chemotherapy-naive patients with breast cancer treated with mastectomy. Samples were stained simultaneously with immunofluorescence for CD44/CD49f/CD133/2 stem cell markers. We assessed the association between CD44+CD49f+CD133/2+ staining in normal adjacent tissue and breast cancer receptor subtype (defined by the expression of the estrogen (ER), progesterone (PR), or human epidermal growth factor-2 (Her2) receptors). We also examined the correlation between CD44+CD49f+CD133/2+ immunofluorescence and each of two previously published gene signatures, one derived from stem-cell enriched tissue and one from BRCA mutated tissue expected to have defective DNA repair.

Results
Patients with triple negative breast cancer (ER–/PR–/HER2–) expressed CD44+CD49f+CD133/2+ in 9 of 9 normal adjacent tissue samples compared with 7 of 52 ER+ and/or Her2+ tumors (P < 0.001). Further, expression of CD44+CD49f+CD133/2+ by normal adjacent tissue correlated positively with a stem cell-derived tumorigenic signature (P <0.001) and inversely with a defective DNA-repair signature (P <0.001).

Conclusion
Normal cells bearing cancer stem cell markers are associated with the triple negative receptor subtype of breast cancer. This study suggests stem cell staining and gene expression signatures from normal breast tissues represent novel tissue-based risk biomarkers for triple negative breast cancer. Validation of these results in additional studies of normal tissue from cancer-free women could lay the foundation for future targeted triple negative breast cancer prevention strategies.
Yield of intermittent versus continuous EEG in comatose survivors of cardiac arrest treated with hypothermia
Authors: Alvarez Vincent , Sierra-Marcos Alba , Oddo Mauro , Rossetti Andrea O 
Published: September 2013

Abstract
Introduction
Electroencephalography (EEG) has a central role in the outcome prognostication in subjects with anoxic/hypoxic encephalopathy following a cardiac arrest (CA). Continuous EEG monitoring (cEEG) has been consistently developed and studied; however, its yield as compared to repeated standard EEG (sEEG) is unknown.

Methods
We studied a prospective cohort of comatose adults treated with therapeutic hypothermia (TH) after a CA. cEEG data regarding background activity and epileptiform components were compared to two 20-minute sEEGs extracted from the cEEG recording (one during TH, and one in early normothermia).

Results
Thirty-four recordings were studied. During TH, the agreement between cEEG and sEEG was 97.1% (95% CI: 84.6 to 99.9%) for background discontinuity and reactivity evaluation, while it was 94.1% (95% CI 80.3 to 99.2%) regarding epileptiform activity. In early normothermia, we did not find any discrepancies. Thus, concordance results were very good during TH (kappa 0.83), and optimal during normothermia (kappa = 1). The median delay between CA and the first EEG reactivity testing was 18 hours (range: 4.75 to 25) for patients with perfect agreement and 10 hours (range: 5.75 to 10.5) for the three patients with discordant findings (P = 0.02, Wilcoxon).

Conclusions
Standard intermittent EEG has comparable performance with continuous EEG both for variables important for outcome prognostication (EEG reactivity) and identification of epileptiform transients in this relatively small sample of comatose survivors of CA. This finding has an important practical implication, especially for centers where EEG resources are limited.
The Median Informs the Message: Accuracy of Individualized Scenarios for Survival Time Based on Oncologists' Estimates
Authors: Kiely Belinda E. , Martin Andrew J. , Tattersall Martin H.N. , Nowak Anna K. , Goldstein David , Wilcken Nicholas R.C. , Wyld David K. , Abdi Ehtesham A. , Glasgow Amanda , Beale Philip J. , Jefford Michael , Glare Paul A. , Stockler Martin R. 
Published: September 2013

Purpose To determine the accuracy and usefulness of oncologists' estimates of survival time in individual patients with advanced cancer. Patients and Methods Twenty-one oncologists estimated the “median survival of a group of identical patients” for each of 114 patients with advanced cancer. Accuracy was defined by the proportions of patients with an observed survival time bounded by prespecified multiples of their estimated survival time. We expected 50% to live longer (or shorter) than their oncologist's estimate (calibration), 50% to live from half to double their estimate (typical scenario), 5% to 10% to live ≤ one quarter of their estimate (worst-case scenario), and 5% to 10% to live three or more times their estimate (best-case scenario). Estimates within 0.67 to 1.33 times observed survival were deemed precise. Discriminative value was assessed with Harrell's C-statistic and prognostic significance with proportional hazards regression. Results Median survival time was 11 months. Oncologists' estimates were relatively well-calibrated (61% shorter than observed), imprecise (29% from 0.67 to 1.33 times observed), and moderately discriminative (Harrell C-statistic 0.63; P = .001). The proportion of patients with an observed survival half to double their oncologist's estimate was 63%, ≤ one quarter of their oncologist's estimate was 6%, and three or more times their oncologist's estimate was 14%. Independent predictors of observed survival were oncologist's estimate (hazard ratio [HR] = 0.92; P = .004), dry mouth (HR = 5.1; P < .0001), alkaline phosphatase more than 101U/L (HR = 2.8; P = .0002), Karnofsky performance status ≤ 70 (HR = 2.3; P = .007), prostate primary (HR = 0.23; P = .002), and steroid use (HR = 2.4; P = .02). Conclusion Oncologists' estimates of survival time were relatively well-calibrated, moderately discriminative, independently associated with observed survival, and a reasonable basis for estimating worst-case, typical, and best-case scenarios for survival.
Identification of Gene Expression–Based Prognostic Markers in the Hematopoietic Stem Cells of Patients With Myelodysplastic Syndromes
Authors: Pellagatti Andrea , Benner Axel , Mills Ken I. , Cazzola Mario , Giagounidis Aristoteles , Perry Janet , Malcovati Luca , Della Porta Matteo G. , Jädersten Martin , Verma Amit , McDonald Emma-Jane , Killick Sally , Hellström-Lindberg Eva , Bullinger Lars , Wainscoat James S. , Boultwood Jacqueline 
Published: September 2013

PurposeThe diagnosis of patients with myelodysplastic syndromes (MDS) is largely dependent on morphologic examination of bone marrow aspirates. Several criteria that form the basis of the classifications and scoring systems most commonly used in clinical practice are affected by operator-dependent variation. To identify standardized molecular markers that would allow prediction of prognosis, we have used gene expression profiling (GEP) data on CD34+ cells from patients with MDS to determine the relationship between gene expression levels and prognosis.Patients and MethodsGEP data on CD34+ cells from 125 patients with MDS with a minimum 12-month follow-up since date of bone marrow sample collection were included in this study. Supervised principal components and lasso penalized Cox proportional hazards regression (Coxnet) were used for the analysis.ResultsWe identified several genes, the expression of which was significantly associated with survival of patients with MDS, including LEF1, CDH1, WT1, and MN1. The Coxnet predictor, based on expression data on 20 genes, outperformed other predictors, including one that additionally used clinical information. Our Coxnet gene signature based on CD34+ cells significantly identified a separation of patients with good or bad prognosis in an independent GEP data set based on unsorted bone marrow mononuclear cells, demonstrating that our signature is robust and may be applicable to bone marrow cells without the need to isolate CD34+ cells.ConclusionWe present a new, valuable GEP-based signature for assessing prognosis in MDS. GEP-based signatures correlating with clinical outcome may significantly contribute to a refined risk classification of MDS.
Multicenter Randomized Trial of Centralized Nurse-Led Telephone-Based Care Coordination to Improve Outcomes After Surgical Resection for Colorectal Cancer: The CONNECT Intervention
Authors: Young Jane M. , Butow Phyllis N. , Walsh Jennifer , Durcinoska Ivana , Dobbins Timothy A. , Rodwell Laura , Harrison James D. , White Kate , Gilmore Andrew , Hodge Bruce , Hicks Henry , Smith Stephen , O'Connor Geoff , Byrne Christopher M. , Meagher Alan P. , Jancewicz Stephen , Sutherland Andrew , Ctercteko Grahame , Pathma-Nathan Nimalan , Curtin Austin , Townend David , Abraham Ned S. , Longfield Greg , Rangiah David , Young Christopher J. , Eyers Anthony , Lee Peter , Fisher Dean , Solomon Michael J. 
Published: September 2013

Purpose To investigate the effectiveness of a centralized, nurse-delivered telephone-based service to improve care coordination and patient-reported outcomes after surgery for colorectal cancer. Patients and Methods Patients with a newly diagnosed colorectal cancer were randomly assigned to the CONNECT intervention or usual care. Intervention-group patients received standardized calls from the centrally based nurse 3 and 10 days and 1, 3, and 6 months after discharge from hospital. Unmet supportive care needs, experience of care coordination, unplanned readmissions, emergency department presentations, distress, and quality of life (QOL) were assessed by questionnaire at 1, 3, and 6 months. Results Of 775 patients treated at 23 public and private hospitals in Australia, 387 were randomly assigned to the intervention group and 369 to the control group. There were no significant differences between groups in unmet supportive care needs, but these were consistently low in both groups at both follow-up time points. There were no differences between the groups in emergency department presentations (10.8% v 13.8%; P = .2) or unplanned hospital readmissions (8.6% v 10.5%; P = .4) at 1 month. By 6 months, 25.6% of intervention-group patients had reported an unplanned readmission compared with 27.9% of controls (P = .5). There were no significant differences in experience of care coordination, distress, or QOL between groups at any follow-up time point. Conclusion This trial failed to demonstrate substantial benefit of a centralized system to provide standardized, telephone follow-up for postoperative patients with colorectal cancer. Future interventions could investigate a more tailored approach.
Are Needs Assessments Cost Effective in Reducing Distress Among Patients With Cancer? A Randomized Controlled Trial Using the Distress Thermometer and Problem List
Authors: Hollingworth William , Metcalfe Chris , Mancero Susana , Harris Susan , Campbell Rona , Biddle Lucy , McKell-Redwood Denise , Brennan James 
Published: September 2013

Purpose Patients with cancer have a high prevalence of distress. We evaluated whether distress monitoring and needs assessment using the Distress Thermometer and Problem List (DT&PL) improved patient outcomes. Patients and Methods We conducted an unblinded, two-arm, parallel randomized controlled trial at two sites among patients starting radiotherapy or chemotherapy. The intervention group completed the DT&PL, rating distress and discussing sources of distress with a trained radiographer/nurse. No specific triage algorithms were followed. The control group received usual care. The main outcome measure was psychological distress (Profile of Mood States [POMS], short form) up to 12 months; secondary outcomes were quality of life (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30) and health care costs. Results Of 220 patients randomly assigned, 112 patients were allocated to the DT&PL. Ninety-five percent completed the primary outcome at 12 months. The DT&PL took 25 minutes; one third of patients had high levels of distress, and most reported physical (84%) or emotional (56%) problems. There was no evidence of an effect of the DT&PL on adjusted POMS scores over follow-up (difference between groups, −1.84; 95% CI, −5.69 to 2.01; P = .35) or in secondary outcomes. The DT&PL cost £19 ($28) per patient and did not lower subsequent health care costs. Few patients (< 3%) in either arm of the trial were referred to a clinical psychologist. Conclusion Patients with cancer have a high prevalence of distress. Needs assessment can be performed quickly and inexpensively. However, the DT&PL was not cost effective in improving patient mood states. It is important to explore the reasons for this so that oncology units can design better services to support patients.
Phase I Study of Quizartinib Administered Daily to Patients With Relapsed or Refractory Acute Myeloid Leukemia Irrespective of FMS-Like Tyrosine Kinase 3–Internal Tandem Duplication Status
Authors: Cortes Jorge E. , Kantarjian Hagop , Foran James M. , Ghirdaladze Darejan , Zodelava Mamia , Borthakur Gautam , Gammon Guy , Trone Denise , Armstrong Robert C. , James Joyce , Levis Mark 
Published: September 2013

Purpose FMS-like tyrosine kinase 3–internal tandem duplication (FLT3-ITD) mutations in acute myeloid leukemia (AML) are associated with early relapse and poor survival. Quizartinib potently and selectively inhibits FLT3 kinase activity in preclinical AML models. Patients and Methods Quizartinib was administered orally at escalating doses of 12 to 450 mg/day to 76 patients (median age, 60 years; range, 23 to 86 years; with a median of three prior therapies [range, 0 to 12 therapies]), enrolled irrespective of FLT3-ITD mutation status in a phase I, first-in-human study in relapsed or refractory AML. Results Responses occurred in 23 (30%) of 76 patients, including 10 (13%) complete remissions (CR) of any type (two CRs, three CRs with incomplete platelet recovery [CRp], five CRs with incomplete hematologic recovery [CRi]) and 13 (17%) with partial remissions (PRs). Of 17 FLT3-ITD–positive patients, nine responded (53%; one CR, one CRp, two CRis, five PRs); of 37 FLT3-ITD–negative patients, five responded (14%; two CRps, three PRs); of 22 with FLT3-ITD–indeterminate/not tested status, nine responded (41%; one CR, three CRis, five PRs). Median duration of response was 13.3 weeks; median survival was 14.0 weeks. The most common drug-related adverse events (> 10% incidence) were nausea (16%), prolonged QT interval (12%), vomiting (11%), and dysgeusia (11%); most were ≤ grade 2. The maximum-tolerated dose was 200 mg/day, and the dose-limiting toxicity was grade 3 QT prolongation. FLT3-ITD phosphorylation was completely inhibited in an in vitro plasma inhibitory assay. Conclusion Quizartinib has clinical activity in patients with relapsed/refractory AML, particularly those with FLT3-ITD, and is associated with an acceptable toxicity profile.
Modifiable Risk Factors and Major Cardiac Events Among Adult Survivors of Childhood Cancer
Authors: Armstrong Gregory T. , Oeffinger Kevin C. , Chen Yan , Kawashima Toana , Yasui Yutaka , Leisenring Wendy , Stovall Marilyn , Chow Eric J. , Sklar Charles A. , Mulrooney Daniel A. , Mertens Ann C. , Border William , Durand Jean-Bernard , Robison Leslie L. , Meacham Lillian R. 
Published: September 2013

Purpose To evaluate the relative contribution of modifiable cardiovascular risk factors on the development of major cardiac events in aging adult survivors of childhood cancer. Patients and Methods Among 10,724 5-year survivors (median age, 33.7 years) and 3,159 siblings in the Childhood Cancer Survivor Study, the prevalence of hypertension, diabetes mellitus, dyslipidemia, and obesity was determined, along with the incidence and severity of major cardiac events such as coronary artery disease, heart failure, valvular disease, and arrhythmia. On longitudinal follow-up, rate ratios (RRs) of subsequent cardiac events associated with cardiovascular risk factors and cardiotoxic therapy were assessed in multivariable Poisson regression models. Results Among survivors, the cumulative incidence of coronary artery disease, heart failure, valvular disease, and arrhythmia by 45 years of age was 5.3%, 4.8%, 1.5%, and 1.3%, respectively. Two or more cardiovascular risk factors were reported by 10.3% of survivors and 7.9% of siblings. The risk for each cardiac event increased with increasing number of cardiovascular risk factors (all Ptrend < .001). Hypertension significantly increased risk for coronary artery disease (RR, 6.1), heart failure (RR, 19.4), valvular disease (RR, 13.6), and arrhythmia (RR, 6.0; all P values < .01). The combined effect of chest-directed radiotherapy plus hypertension resulted in potentiation of risk for each of the major cardiac events beyond that anticipated on the basis of an additive expectation. Hypertension was independently associated with risk of cardiac death (RR, 5.6; 95% CI, 3.2 to 9.7). Conclusion Modifiable cardiovascular risk factors, particularly hypertension, potentiate therapy-associated risk for major cardiac events in this population and should be the focus of future interventional studies.
Predicting Tumor Control After Resection Bed Radiosurgery of Brain Metastases
Authors: Luther Neal , Kondziolka Douglas , Kano Hideyuki , Mousavi Seyed H. , Engh Johnathan A. , Niranjan Ajay , Flickinger John C. , Lunsford L. Dade 
Published: September 2013

Abstract

BACKGROUND:
Stereotactic radiosurgery (SRS) to the resection bed of a brain metastasis is an important treatment option.

OBJECTIVE:
To identify factors associated with tumor progression after SRS of the resection bed of a brain metastasis and to evaluate patterns of failure for patients who eventually had tumor progression.

METHODS:
We performed a retrospective analysis of 120 patients who underwent tumor bed radiosurgery after an initial gross total resection. The mean imaging follow-up time was 55 weeks. The median margin dose was 16 Gy. Forty-seven patients (39.2%) underwent whole-brain radiation therapy before or shortly after SRS.

RESULTS:
Local tumor control was achieved in 103 patients (85.8%). Progression-free survival was 96% at 6 months, 87% at 12 months, and 74% at 24 months. Recurrence most commonly occurred deep in the cavity (65%) outside the planned treatment volume (PTV) margin (53%). PTV, cavity diameter, and a margin dose &lt; 16 Gy significantly correlated with local failure. For patients with PTVs ≥ 8.0 cm3, local progression-free survival declined to 93% at 6 months, 83% at 12 months, and 65% at 24 months. Development or progression of distant metastases occurred in 40% of patients. Whole-brain radiation therapy was not associated with improved local control.

CONCLUSION:
Resection bed SRS for brain metastases provided excellent local control. The cavity PTV is predictive of tumor control. Because failure usually occurs outside the PTV, inclusion of a judicious 2- to 3-mm margin beyond the area of postoperative enhancement may be prudent.