nils-herrmann/clean_scirepeval huggingface dataset:
Increased myelotoxicity of idarubicin: Is there a pharmacological basis?

Clinical trials evaluating idarubicin (IDA) in acute myeloid leukemia, multiple myeloma and non-Hodgkin's lymphoma (NHL) have provided some evidence for an increased myelotoxicity of IDA compared to other anthracyclines. IDA is known to be less sensitive towards multidrug resistance mediated by P-glycoprotein (P-gp). This phenotype is a major impediment to successful antineoplastic treatment, but P-gp is also expressed on hematopoietic stem cells ( We investigated the pharmacokinetics of IDA and etoposide (ETO) in seven previously untreated patients with aggressive NHL. The patients received a CHOP-derived protocol (CIVEP) in which doxorubicin (DOX) was substituted by IDA 11–16 mg/m2 and ETO 3×100 mg/m2 was added. Furthermore, we evaluated in vitro the impact of P-gp expression on the cytotoxicity of DOX and IDA in cells from three parental chemosensitive leukemia and lymphoma cell lines (HL60, U937, CCRF) and their resistant sublines, as well as in CD34-positive HSC.Results: The peak plasma levels (Cmax), terminal elimination half-life (t1/2) and area under the concentration curve (AUC) both for IDA and for ETO did not differ from published data. In cell line models the numbers of viable cells in a P-gp-expressing resistant CCRF-VCR100 subline were significantly more reduced by IDA (P<0.001), but there was no difference in the cytotoxicities of IDA and DOX in chemosensitive CCRF cells and in the (non-P-gp-expressing) resistant U937 and HL60 sublines. Cytotoxicity against HSC was more pronounced after incubation with IDA than after treatment with DOX (P=0.014), even when a tenfold higher concentration of DOX than of IDA was used. The addition of cyclosporin A increased the cytotoxic effect of DOX but not that of IDA in  The pharmacokinetics of IDA and its main metabolite idarubicinol in CHOP-derived protocols were not different from data obtained with other combinations or monotherapy. The increased myelotoxicity of IDA may be a consequence of P-gp expression in CD34-positive HSC.
The metabolic hormone FGF21 is associated with endothelial dysfunction in hemodialysis patients

Finding new, reliable biomarkers of cardiovascular risk in hemodialysis (HD) patients is of utmost importance. Fibroblast growth factor 21 (FGF21) has been recently associated with atherosclerosis in the general population. The relationship between markedly elevated FGF21 levels in HD patients and endothelial dysfunction is unknown. The aim of the study was to assess the determinants of FGF21, the correlation between FGF21 and tumor necrosis factor TNF-like weak inducer of apoptosis (sTWEAK) and the correlation between FGF21 and endothelial dysfunction in HD patients. A cross-sectional observational study was conducted in 70 HD patients (mean age 59.9 ± 12.5 years, 14.3% diabetes mellitus, 57.1% male) from Nefromed Dialysis Center Cluj. We registered clinical and biological data, and serum FGF21 levels were measured by ELISA. Endothelial function was evaluated by brachial flow-mediated dilation (FMD). An analysis based on stratification of FGF21 values into quartiles was performed. FGF21 levels were directly correlated with sTWEAK, tricipital skinfold thickness (TST), systolic blood pressure (SBP), total cholesterol and triglycerides. In multivariate linear analysis, only sTWEAK and SBP remained significantly associated with FGF21. FGF21 values in the inferior quartile were directly correlated with HDL-cholesterol, while FGF21 values in the superior quartile were directly correlated with SBP, pulse pressure and sTWEAK. FMD was significantly higher in the inferior quartile as compared to the superior quartile. High FGF21 values in our patients are correlated with atherosclerosis risk factors: hypercholesterolemia, hypertriglyceridemia, hypertension, increased TST and increased levels of sTWEAK. Endothelial dysfunction is associated with high FGF21 in HD patients.
Disease duration of rheumatoid arthritis is a predictor of vascular stiffness: a cross-sectional study in patients without known cardiovascular comorbidities

The aim of this study was to analyze the impact of disease duration on carotid to femoral pulse wave velocity (cfPWV) in rheumatoid arthritis (RA) patients without either known traditional cardiovascular risk factors or previous comorbidities.Patients with RA diagnosis attending the rheumatology outpatient clinic of Hospital Civil Juan I. Menchaca, Guadalajara, Mexico, were analyzed. A total of 106 RA patients without known traditional cardiovascular risk factors were selected. All subjects were evaluated for RA disease duration, RA disease activity score on 28 joints (DAS28), serum lipids, rheumatoid factor and anti-cyclic citrullinated peptide (anti-CCP) antibodies. Arterial stiffness was measured as cfPWV by noninvasive tonometry. A multivariate regression model was used to analyze the contribution of RA disease duration and age on cfPWV. cfPWV was positively correlated with age (r = 0.450, P < .001), RA disease duration (r = 0.340, P < .001), total cholesterol (r = 0.312, P = .002), and low density lipoprotein (LDL-c) cholesterol (r = 0.268, P = .012). Patients with a RA disease duration ≥10 years exhibited significantly increased cfPWV compared with patients with disease duration <2 years (8.4 ± 1.8 vs 7.0 ± 0.8) and ≥2 to <10 years (8.4 ± 1.8 vs 7.8 ± 1.3), respectively. Age, RA disease duration, and triglycerides were predictors of cfPWV in multivariate analyses. According to the β-coefficients, each year of disease duration (β = 0.072) had a greater impact on cfPWV than age (β = 0.054).Each year of life with RA contributes to a higher rate of vascular aging or stiffening than a year of life without RA. The cumulative damage provided by RA was most pronounced in patients with disease duration ≥10 years.
Helium-oxygen decreases inspiratory effort and work of breathing during pressure support in intubated patients with chronic obstructive pulmonary disease

To evaluate the impact of helium-oxygen (He/O2) on inspiratory effort and work of breathing (WOB) in intubated COPD patients ventilated with pressure support. Prospective crossover interventional study in the medical ICU of a university hospital. Ten patients. Sequential inhalation (30 min each) of three gas mixtures: (a) air/O2, (b) He/O2 (c) air/O2, at constant FIO2 and level of pressure support. Inspiratory effort and WOB were determined by esophageal and gastric pressure. Throughout the study pressure support and FIO2 were 14±3 cmH2O and 0.33±0.07 respectively. Compared to Air/O2, He/O2 reduced the number of ineffective breaths (4±5 vs. 9±5 breaths/min), intrinsic PEEP (3.1±2 vs. 4.8±2 cmH2O), the magnitude of negative esophageal pressure swings (6.7±2 vs. 9.1±4.9 cmH2O), pressure-time product (42±37 vs. 67±65 cmH2O s−1 min−1), and total WOB (11±3 vs. 18±10 J/min). Elastic (6±1 vs. 10±6 J/min) and resistive (5±1 vs. 9±4 J/min) components of the WOB were decreased by He/O2. In intubated COPD patients ventilated with pressure support He/O2 reduces intrinsic PEEP, the number of ineffective breaths, and the magnitude of inspiratory effort and WOB. He/O2 could prove useful in patients with high levels of PEEPi and WOB ventilated in pressure support, for example, during weaning.
Do patients with active RA have differences in disease activity and perceptions if anti-TNF naïve versus anti-TNF experienced? Baseline results of the optimization of adalimumab trial

The chance of a good response in RA is attenuated in previous anti-TNF users who start new anti-TNF therapy compared to biologic naïve patients. In active RA, those with previous anti-TNF exposure compared to anti-TNF naïve may have different baseline disease activity and patient perceptions when starting a new anti-TNF treatment that could explain the observed response differences.



The aim of this study was a post hoc analysis of baseline characteristics of patients enrolled in the Optimization of Adalimumab study that was a treat to target vs. routine care study in patients initiating adalimumab. As per the protocol, a maximum of 20% anti-TNF experienced patients were enrolled in the 300 patient trial. Twelve (4.0%) were excluded who previously used other biologics. Baseline characteristics including age, gender, tender and swollen joint counts, disease activity (DAS28), function (HAQ-DI), patient global assessment, patient satisfaction with current treatment, and inflammatory markers (CRP, ESR), were compared between previously anti-TNF experienced [etanercept or infliximab (EXP)], and anti-TNF naïve patients (NAÏVE).



The mean (SD) age was 54.8 (13.3) years; 81.0% were female, and 237 (79.0%) were anti-TNF naïve while 51 (17.0%) patients were anti-TNF experienced (29 with etanercept, 16 with infliximab, and 6 for both). The mean (SD) baseline in EXP versus NAÏVE groups respectively was: CRP=21.7(32.9) vs. 17.5(20.7); ESR=28.7(22.5) vs. 29.8(20.4); SJC=10.5(6.0) vs. 10.7(5.6); TJC=12.8(7.1) vs. 12.3(7.3); and DAS28=6.0(1.2) vs. 5.8(1.1). None of the between-group differences were statistically significant, however, the HAQ-DI in EXP was 1.7(0.6) compared to 1.5(0.7) for the NAÏVE (P=0.021). Additionally, EXP patients had a higher patient global score [71.3(26.1) vs. 61.9(26.2), P=0.021].



Although anti-TNF naïve and experienced patients who initiated adalimumab were similar, with respect to several baseline characteristics, significant differences in subjective measures were observed, which may indicate more severe patient measures (function and global disease activity) in anti-TNF experienced patients.
Immediate anatomic results after the endovascular treatment of unruptured intracranial aneurysms: analysis of the ATENA series.

A precise analysis of the immediate postoperative anatomic results in a large series of unruptured intracranial aneurysms treated by endovascular approach has not previously been presented. This study aimed to assess the efficacy of endovascular treatment of unruptured intracranial aneurysms in light of immediate postoperative anatomic results in a prospective, multicenter study (the Analysis of Treatment by Endovascular Approach of Nonruptured Aneurysms study; ATENA).



Postoperative anatomic results from digital subtraction angiography (DSA) were evaluated with the Montreal scale by the treating physician and by 2 anonymous, independent, experienced neuroradiologists.



The analysis included 622 patients (449 women, 173 men; age range, 22-83 years; mean age, 51.2 +/- 11.3 years) harboring 694 aneurysms. Evaluation of the postoperative anatomic results by the 2 independent reviewers indicated total occlusions in 437 aneurysms (63.0%), neck remnants in 156 aneurysms (22.5%), and aneurysm remnants in 101 aneurysms (14.6%). Several factors favorably affected the quality of the aneurysm occlusion with treatment, including patient age (< 65 years old; P < .0001), aneurysm diameter (<or= 6 mm; P = .0049), aneurysm dome-to-neck ratio (> 1.5; P = .0388), and endovascular technique (coiling or remodelling compared with stent placement; P = .0001).



The endovascular treatment of unruptured aneurysms provided satisfactory postoperative occlusion rates, with a high percentage of complete occlusion or neck remnants (85.4%). Postoperative anatomic results were significantly affected by aneurysm size and neck size, but not aneurysm location.
EURObservational Research Programme: the Heart Failure Pilot Survey (ESC-HF Pilot).

The primary objective of the new ESC-HF Pilot Survey was to describe the clinical epidemiology of outpatients and inpatients with heart failure (HF) and the diagnostic/therapeutic processes applied across 12 participating European countries. This pilot study was specifically aimed at validating the structure, performance, and quality of the data set, for continuing the survey into a permanent registry.



The ESC-HF Pilot study is a prospective, multicentre, observational survey conducted in 136 cardiology centres from 12 European countries selected to represent the different health systems and care attitudes across Europe. All outpatients with HF and patients admitted for acute HF were included during the enrolment period (1 day per week for 8 consecutive months). From October 2009 to May 2010, 5118 patients were included in this pilot survey, of which 1892 (37%) were admitted for acute HF and 3226 (63%) for chronic HF. Ischaemic aetiology was reported in about half of the patients. In patients admitted for acute HF, the most frequent clinical profile was decompensated HF (75% of cases), whereas pulmonary oedema and cardiogenic shock were reported, respectively, in 13.3 and 2.3% of the cases. The total in-hospital mortality rate was 3.8% and was cardiovascular in 90.1% of the cases. Lowest and highest mortality rates were observed in hypertensive HF and in cardiogenic shock, respectively. More than 80% of patients with chronic HF were treated with renin-angiotensin-aldosterone system blockers and β-adrenergic blockers. However, target doses of such drugs were reached in one-third to one-fourth of the patients only.



The ESC-HF Pilot Survey is an example of the possibility of utilizing an observational methodology to get insights into the current clinical practice in Europe, whose picture will be completed by the 1-year follow-up. Moreover, this study offered the opportunity to refine the organizational structure of a long-term, extended European network.
Using HPV prevalence to predict cervical cancer incidence.

Knowledge of a country's cervical cancer (CC) burden is critical to informing decisions about resource allocation to combat the disease; however, many countries lack cancer registries to provide such data. We developed a prognostic model to estimate CC incidence rates in countries without cancer registries, leveraging information on human papilloma virus (HPV) prevalence, screening, and other country-level factors. We used multivariate linear regression models to identify predictors of CC incidence in 40 countries. We extracted age-specific HPV prevalence (10-year age groups) by country from a meta-analysis in women with normal cytology (N = 40) and matched to most recent CC incidence rates from Cancer Incidence in Five Continents when available (N = 36), or Globocan 2008 (N = 4). We evaluated country-level behavioral, economic, and public health indicators. CC incidence was significantly associated with age-specific HPV prevalence in women aged 35-64 (adjusted R-squared 0.41) ("base model"). Adding geographic region to the base model increased the adjusted R-squared to 0.77, but the further addition of screening was not statistically significant. Similarly, country-level macro-indicators did not improve predictive validity. Age-specific HPV prevalence at older ages was found to be a better predictor of CC incidence than prevalence in women under 35. However, HPV prevalence could not explain the entire CC burden as many factors modify women's risk of progression to cancer. Geographic region seemed to serve as a proxy for these country-level indicators. Our analysis supports the assertion that conducting a population-based HPV survey targeting women over age 35 can be valuable in approximating the CC risk in a given country.
Using program metadata to support SDT in object-oriented applications

Software dynamic translation (SDT) is a powerful technology that enables software malleability and adaptivity at the instruction level by providing facilities for run-time monitoring and code modification. SDT has been used as the basis for many valuable tools, including dynamic optimizers, profilers, security policy enforcement, and binary translation to name a few. However, modern object-oriented programming techniques and their implementations (e.g., virtual functions, exceptions, dynamic code, etc.) pose unique challenges to high performing SDT systems. In this paper, we present Metaman, a generalized program metadata manager that stores and manages program information so that it can be efficiently accessed by emerging SDT systems to improve overall runtime performance of a managed executable. Using the information collected by Metaman, the run-time performance of an existing SDT system was improved by 22% making its execution speed only 3% slower than native (i.e., non-managed) execution.
Role of FDG-PET in the implementation of involved-node radiation therapy for Hodgkin lymphoma patients.

This study examines the role of (18)F-labeled fluorodeoxyglucose positron emission tomography (FDG-PET) in the implementation of involved-node radiation therapy (INRT) in patients treated for clinical stages (CS) I/II supradiaphragmatic Hodgkin lymphoma (HL).



Patients with untreated CS I/II HL enrolled in the randomized EORTC/LYSA/FIL Intergroup H10 trial and participating in a real-time prospective quality assurance program were prospectively included in this study. Data were electronically obtained from 18 French cancer centers. All patients underwent APET-computed tomography (PET-CT) and a post-chemotherapy planning CT scanning. The pre-chemotherapy gross tumor volume (GTV) and the postchemotherapy clinical target volume (CTV) were first delineated on CT only by the radiation oncologist. The planning PET was then co-registered, and the delineated volumes were jointly analyzed by the radiation oncologist and the nuclear medicine physician. Lymph nodes undetected on CT but FDG-avid were recorded, and the previously determined GTV and CTV were modified according to FDG-PET results.



From March 2007 to February 2010, 135 patients were included in the study. PET-CT identified at least 1 additional FDG-avid lymph node in 95 of 135 patients (70.4%; 95% confidence interval [CI]: 61.9%-77.9%) and 1 additional lymph node area in 55 of 135 patients (40.7%; 95% CI: 32.4%-49.5%). The mean increases in the GTV and CTV were 8.8% and 7.1%, respectively. The systematic addition of PET to CT led to a CTV increase in 60% of the patients.



Pre-chemotherapy FDG-PET leads to significantly better INRT delineation without necessarily increasing radiation volumes.
Elevated concentration of placental growth factor (PlGF) and long term risk in patients with acute coronary syndrome in the PROVE IT-TIMI 22 trial

Placental growth factor (PlGF), a member of the vascular endothelial growth factor (VEGF) family, acts via the flt-1 receptor and promotes endothelial activation and macrophage recruitment into atherosclerotic lesions. We investigated the relationship of PlGF with cardiovascular outcomes in a large cohort of patients presenting across the spectrum of ACS. PlGF was measured at baseline (n = 3,761) and at four-months (n = 3,369) in patients randomized to atorvastatin 80 mg or pravastatin 40 mg after ACS in the PROVE IT-TIMI 22 trial. The primary endpoint was death, myocardial infarction (MI), unstable angina, revascularization or stroke (mean follow-up 24 months). Elevated baseline PlGF was associated with a higher incidence of the primary endpoint through 2 years (Q1 vs. Q5: 18.7 vs. 29.3%, p < 0.0001). The risk of death or MI was also higher in patients with elevated baseline PlGF (Q1 vs. Q5: 7.0 vs. 11.6%, p = 0.029). Adjusting for baseline characteristics and risk factors, elevated baseline PlGF was independently associated with the risk of the primary endpoint (adjusted-HR for Q5 vs. Q1 1.45; 95% CI 1.16–1.83; p = 0.001). Elevated PlGF at four months was associated with higher risk of death or MI (Adjusted HR Q5 vs. Q1 2.79, 95% CI: 1.37–5.68; p = 0.005), and higher risk of the primary endpoint (Adjusted HR Q5 vs. Q1 1.78, 95% CI: 1.26–2.51; p = 0.001). Higher concentration of PlGF after ACS is associated with long-term risk of recurrent cardiovascular events independent of traditional risk factors. This association is present early after ACS and appears to be stronger at four months.
Renal denervation improves exercise blood pressure: insights from a randomized, sham-controlled trial

Despite the ongoing debate on the role of renal sympathetic denervation (RSD) in the management of therapy-resistant hypertension, little is known about its possible effects on exercise blood pressure (BP), a known predictor for future cardiovascular events. We sought to evaluate the effect of RSD on exercise BP in a randomized, sham-controlled trial in patients with mild hypertension. Patients with therapy-resistant mild hypertension (defined by mean daytime systolic BP between 135 and 149 mmHg or mean daytime diastolic BP between 90 and 94 mmHg on 24-h ambulatory BP measurement) were randomized to either radiofrequency-based RSD or a sham procedure. Patients underwent cardiopulmonary exercise testing at baseline and after 6 months. Of the 71 patients randomized, data from cardiopulmonary exercise testing were available for 48 patients (22 in the RSD group, 26 in the sham group). After 6 months, patients undergoing RSD had a significantly lower systolic BP at maximum exercise workload compared to baseline (−14.2 ± 26.1 mmHg, p = 0.009). In contrast, no change was observed in the sham group (0.6 ± 22.9 mmHg, p = 0.45, p = 0.04 for between-group comparison). When analyzing patients with exaggerated baseline exercise BP only, the effect was even more pronounced (RSD vs. sham −29.5 ± 23.4 vs. 0.1 ± 25.3 mmHg, p = 0.008). Exercise systolic BP values in patients with mild therapy-resistant hypertension are reduced after RSD as compared to a sham-procedure.
Effects of theophylline on plasma levels of interleukin-4, cyclic nucleotides and pulmonary functions in patients with chronic obstructive pulmonary disease

In order to measure the plasma levels of interleukin-4 (IL-4). cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) in patients with chronic obstructive pulmonary disease (COPD) and observe the effects of oral theophylline on them, we divided 28 COPD patients into COPD experimental group and COPD control group. Plasma levels of IL-4, cAMP and cGMP as well as parameters of pulmonary function tests were measured in these 2 groups before and after 2 weeks of treatment with oral theophylline (Protheo, 400 mg, qd) or placebo. Plasma levels of IL-4 and cGMP were significantly elevated in patients with COPD as compared with normal controls (P< 0. 05), while cAMP and cAMP/cGMP were significantly lower than those in controls (P < 0. 01). Plasma level of IL-4 was inversely correlated with forced expiratory volume at the first second (FEV1) and with maximum expiratory flow rate at 50 % of forced vital capacity (V50) (bothr= −0.46,P< 0.05) while it was directly correlated with the scores of the clinical manifestations (r=0.57,P< 0.05) in COPD patients. Two weeks after treatment with theophylline, IL-4 and cGMP in COPD experimental group were decreased significantly while cAMP and cAMP/ cGMP increased significantly (P< 0. 05). The change of IL-4 was inversely correlated with the changes of FEV1, and V50(r=−0.53 and -0.54, respectively,P< 0. 05). Two weeks after placebo treatment, the COPD control group did not show such changes. We are led to conclude that IL-4 might play a role in the pathogenesis of the airway inflammation and air flow limitation in COPD patients and the mechanisms of theophylline’s therapeutic efrects of attenuating air-flow limitation may partially depend on its anti-inflammatory effects on the airways which, in turn, is dependent on its inhibitory effects on some inflammatory mediators such as IL-4.