nils-herrmann/clean_scirepeval huggingface dataset:
Urinary hepcidin-25 and risk of acute kidney injury following cardiopulmonary bypass.

Acute kidney injury (AKI) complicating cardiopulmonary bypass (CPB) results in increased morbidity and mortality. Urinary hepcidin-25 has been shown to be elevated in patients who do not develop AKI after CPB using semiquantitative mass spectrometry (SELDI TOF-MS). The goals of this study were to quantitatively validate these findings with ELISA and evaluate the diagnostic performance of hepcidin-25 for AKI.



A nested, case-control analysis of urinary hepcidin-25 in AKI (n = 22) and non-AKI (n = 22) patients was conducted to validate the SELDI TOF-MS data at the following times: preoperatively; the start of CPB; 1 hour on CPB; on arrival to the intensive care unit; and postoperative days (POD) 1 and 3 to 5. The diagnostic performance of hepcidin-25 was then evaluated in the entire prospective observational cohort (n = 338) at POD 1. AKI was defined as Cr >50% from baseline, within 72 hours postoperatively.



Urinary hepcidin-25/Cr ratio was significantly elevated in all patients at POD 1 compared with baseline (P < 0.0005) and was also significantly elevated in non-AKI versus AKI patients at POD 1 (P < 0.0005). Increased log(10) hepcidin-25/Cr ratio was strongly associated with avoidance of AKI on univariate analysis. On multivariate analysis, the log(10) hepcidin-25/Cr ratio (P < 0.0001) was associated with avoidance of AKI with an area under the curve of 0.80, sensitivity 0.68, specificity 0.68, and negative predictive value 0.96.



Elevated urinary hepcidin-25 on POD 1 is a strong predictor of avoidance of AKI beyond postoperative day 1.
Homeopathy for Depression: A Randomized, Partially Double-Blind, Placebo-Controlled, Four-Armed Study (DEP-HOM)

The specific clinical benefit of the homeopathic consultation and of homeopathic remedies in patients with depression has not yet been investigated.



To investigate the 1) specific effect of individualized homeopathic Q-potencies compared to placebo and 2) the effect of an extensive homeopathic case taking (case history I) compared to a shorter, rather conventional one (case history II) in the treatment of acute major depression (moderate episode) after six weeks.



A randomized, partially double-blind, placebo-controlled, four-armed trial using a 2×2 factorial design with a six-week study duration per patient was performed.



A total of 44 from 228 planned patients were randomized (2∶1∶2∶1 randomization: 16 homeopathic Q-potencies/case history I, 7 placebo/case history I, 14 homeopathic Q-potencies/case history II, 7 placebo/case history II). Because of recruitment problems, the study was terminated prior to full recruitment, and was underpowered for the preplanned confirmatory hypothesis testing. Exploratory data analyses showed heterogeneous and inconclusive results with large variance in the sample. The mean difference for the Hamilton-D after 6 weeks was 2.0 (95%CI -1.2;5.2) for Q-potencies vs. placebo and -3.1 (-5.9;-0.2) for case history I vs. case history II. Overall, no consistent or clinically relevant results across all outcomes between homeopathic Q-potencies versus placebo and homeopathic versus conventional case taking were observed. The frequency of adverse events was comparable for all groups.



Although our results are inconclusive, given that recruitment into this trial was very difficult and we had to terminate early, we cannot recommend undertaking a further trial addressing this question in a similar setting. Prof. Dr. Claudia Witt had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
Selective COX-2 inhibition improves endothelial function in coronary artery disease.

There is an ongoing debate as to whether the gastrointestinal safety of COX-2 inhibition compared with nonsteroidal antiinflammatory drugs (NSAIDs) may come at the cost of increased cardiovascular events. In view of the large number of patients at cardiovascular risk requiring chronic analgesic therapy with COX-2 inhibitors for arthritic and other inflammatory conditions, the effects of selective COX-2 inhibition on clinically useful surrogates for cardiovascular disease, particularly endothelial function, need to be determined.



Fourteen male patients (mean age, 66+/-3 years) with severe coronary artery disease (average of 2.6 vessels with stenosis >75%) undergoing stable background therapy with aspirin and statins were included. The patients received celecoxib (200 mg BID) or placebo for a duration of 2 weeks in a double-blind, placebo-controlled, crossover fashion. After each treatment period, flow-mediated dilation of the brachial artery, high-sensitivity C-reactive protein, oxidized LDL, and prostaglandins were measured. Celecoxib significantly improved endothelium-dependent vasodilation compared with placebo (3.3+/-0.4% versus 2.0+/-0.5%, P=0.026), whereas endothelium-independent vasodilation, as assessed by nitroglycerin, remained unchanged (9.0+/-1.6% versus 9.5+/-1.3%, P=0.75). High-sensitivity C-reactive protein was significantly lower after celecoxib (1.3+/-0.4 mg/L) than after placebo (1.8+/-0.5 mg/L, P=0.019), as was oxidized LDL (43.6+/-2.4 versus 47.6+/-2.6 U/L, P=0.028), whereas prostaglandins did not change.



This is the first study to demonstrate that selective COX-2 inhibition improves endothelium-dependent vasodilation and reduces low-grade chronic inflammation and oxidative stress in coronary artery disease. Thus, selective COX-2 inhibition holds the potential to beneficially impact outcome in patients with cardiovascular disease.
Nitrous Oxide and Serious Long-term Morbidity and Mortality in the Evaluation of Nitrous Oxide in the Gas Mixture for Anaesthesia (ENIGMA)-II Trial.

The Evaluation of Nitrous Oxide in the Gas Mixture for Anaesthesia (ENIGMA)-II trial randomly assigned 7,112 noncardiac surgery patients at risk of perioperative cardiovascular events to 70% N2O or 70% N2 groups. The aim of this follow-up study was to determine the effect of nitrous oxide on a composite primary outcome of death and major cardiovascular events at 1 yr after surgery.



One-year follow-up was conducted via a medical record review and telephone interview. Disability was defined as a Katz index of independence in activities of daily living score less than 8. Adjusted odds ratios and hazard ratios were calculated as appropriate for primary and secondary outcomes.



Among 5,844 patients evaluated at 1 yr, 435 (7.4%) had died, 206 (3.5%) had disability, 514 (8.8%) had a fatal or nonfatal myocardial infarction, and 111 (1.9%) had a fatal or nonfatal stroke during the 1-yr follow-up period. Exposure to nitrous oxide did not increase the risk of the primary outcome (odds ratio, 1.08; 95% CI, 0.94 to 1.25; P = 0.27), disability or death (odds ratio, 1.07; 95% CI, 0.90 to 1.27; P = 0.44), death (hazard ratio, 1.17; 95% CI, 0.97 to 1.43; P = 0.10), myocardial infarction (odds ratio, 0.97; 95% CI, 0.81 to 1.17; P = 0.78), or stroke (odds ratio, 1.08; 95% CI, 0.74 to 1.58; P = 0.70).



These results support the long-term safety of nitrous oxide administration in noncardiac surgical patients with known or suspected cardiovascular disease.
Amino Acid Intakes Are Associated With Bone Mineral Density and Prevalence of Low Bone Mass in Women: Evidence From Discordant Monozygotic Twins

Although a higher protein intake, particularly from vegetable sources, has been shown to be associated with higher bone mineral density (BMD) the relative impact of specific amino acids on BMD and risk of osteoporosis remains to be determined. Mechanistic research suggests that a number of specific amino acids, including five nonessential amino acids--alanine, arginine, glutamic acid, glycine, and proline--may play a role in bone health, principally through improved production of insulin and insulin-like growth factor 1 and the synthesis of collagen and muscle protein. However to date, no previous studies have examined the associations between habitual intake of amino acids and direct measures of BMD and prevalence of osteoporosis or osteopenia, and no studies have examined this relationship in discordant identical twin-pairs. In these analyses of female monozygotic twin-pairs discordant for amino acid intake (n = 135), twins with higher intakes of alanine and glycine had significantly higher BMD at the spine than their co-twins with within-pair differences in spine-BMD of 0.012 g/cm(2) (SE 0.01; p = 0.039) and 0.014 g/cm(2) (SE 0.01; p = 0.026), respectively. Furthermore, in cross-sectional multivariable analyses of 3160 females aged 18 to 79 years, a higher intake of total protein was significantly associated with higher DXA-measured BMD at the spine (quartile Q4 to quartile Q1: 0.017 g/cm(2), SE 0.01, p = 0.035) and forearm (Q4 to Q1: 0.010 g/cm(2), SE 0.003, p = 0.002). Intake of six amino acids (alanine, arginine, glutamic acid, leucine, lysine, and proline) were associated with higher BMD at the spine and forearm with the strongest association observed for leucine (Q4 to Q1: 0.024 g/cm(2), SE 0.01, p = 0.007). When intakes were stratified by protein source, vegetable or animal, prevalence of osteoporosis or osteopenia was 13% to 19% lower comparing extreme quartiles of vegetable intake for five amino acids (not glutamic acid or proline). These data provide evidence to suggest that intake of protein and several amino acids, including alanine and glycine, may be beneficial for bone health, independent of genetic background.
Cytokine profile in quadriceps muscles of patients with severe COPD.

Systemic proinflammatory cytokines and oxidative stress have been described in association with peripheral muscle wasting and weakness of patients with severe chronic obstructive pulmonary disease (COPD), but their expression in skeletal muscle is unknown. The objectives of the present study were to determine muscle protein levels of selected cytokines in patients with COPD and to study their relationships with protein carbonylation as a marker of oxidative stress, quadriceps function and exercise capacity.



We conducted a cross sectional study in which 36 cytokines were detected using a human antibody array in quadriceps specimens obtained from 19 patients with severe COPD and seven healthy controls. Subsequently, selected cytokines (tumour necrosis factor (TNF)alpha, TNFalpha receptors I and II, interleukin (IL) 6, interferon gamma, transforming growth factor (TGF) beta and vascular endothelial growth factor (VEGF)), as well as protein carbonylation (oxidative stress index) were determined using an enzyme linked immunosorbent assay (ELISA) in all muscles.



Compared with controls, the vastus lateralis of patients with COPD showed significantly lower protein ELISA levels of TNFalpha, which positively correlated with their quadriceps function, TNFalpha receptor II and VEGF. Protein ELISA levels of IL6, interferon gamma and TGFbeta did not differ between patients and controls. Quadriceps protein carbonylation was greater in patients and inversely correlated with quadriceps strength among them.



These findings do not support the presence of a proinflammatory environment within the quadriceps muscles of clinically and weight stable patients with severe COPD, despite evidence for increased oxidative stress and the presence of muscle weakness.
Sex-specific associations of cardiovascular risk factors with carotid stiffness--results from the SAPALDIA cohort study.

Manifestation of cardiovascular disease (CVD) occurs with clear sex differences. Carotid stiffness (CS) parameters are increasingly used for CVD risk assessment but the sex-specific association with CVD risk factors as well as association patterns between CS parameters are largely unknown, which we investigated in SAPALDIA population-based cohort participants.



Risk factors of 2545 participants without clinically manifest disease were evaluated in 2001-2003 and different CS parameters were assessed in carotid ultrasound scans in 2010-2011. Stratified and non-stratified mixed linear models and multivariate regression analyses were used to examine sex-specific associations, differences and association patterns of single risk factors and CS parameters.



HDL cholesterol was the only significant protective determinant of reduced CS for both sexes (ranges of CS parameters: -3.7; -0.8% of changes in geometric mean per 1SD of the risk factor on an inverted scale) and significant adverse risk factors were BMI (-0.5; 4.7%), systolic (-1.23; 4.7%) and diastolic blood pressure (1.4; 4.4%), heart rate (2.7; 7.9%), C-reactive protein (0.6; 3.3%) and smoking (-2.82; 1%), all p-values of multivariate analyses were <0.01. Sex differences with stiffer CS parameters in men were observed for increased heart rate (p = 0.001) and LDL cholesterol (p < 0.001) and in women for triglyceride (p < 0.003). Similar association patterns were found for most CS parameters.



Sex-specific associations of cardiovascular risk factors may reflect a sex-specific burden of atherosclerotic risk factors and similar association patterns across different CS parameters within men and women may allow the use of CS parameters in an exchangeable manner.
Fludarabine, cyclophosphamide, and rituximab chemoimmunotherapy is highly effective treatment for relapsed patients with CLL.

Optimal management of patients with relapsed/refractory chronic lymphocytic leukemia (CLL) is dictated by patient characteristics, prior therapy, and response to prior therapy. We report the final analysis of combined fludarabine, cyclophosphamide, and rituximab (FCR) for previously treated patients with CLL and identify patients who benefit most from this therapy. We explore efficacy of FCR in patients beyond first relapse, patients with prior exposure to fludarabine and alkylating agent combinations, and patients with prior exposure to rituximab. The FCR regimen was administered to 284 previously treated patients with CLL. Patients were assessed for response and progression by 1996 National Cancer Institute-Working Group (NCI-WG) criteria for CLL and followed for survival. The overall response rate was 74%, with 30% complete remission. The estimated median overall survival was 47 months and median progression-free survival for all patients was 21 months. Subgroup analyses indicated that the following patients were most suitable for FCR treatment: patients with up to 3 prior treatments, fludarabine-sensitive patients irrespective of prior rituximab exposure, and patients without chromosome 17 abnormalities. FCR is an active and well-tolerated therapy for patients with relapsed CLL. The addition of rituximab to FC improved quality and durability of response in this patient population.
Acetabular component position of the noncemented total hip endoprosthesis after previous Chiari pelvic osteotomy.

The aim of the study was to determine the validity of acetabular component position of the noncemented total hip endoprosthesis after Chiari pelvic osteotomy.



The study involved 75 patients operated on at the Institute of Orthopedic Surgery "Banjica" in the period from 1990-2009. The first group consisted of 39 patients (46 hips) who underwent Chiari pelvic osteotomy and also later the implantation of a noncemented total hip endoprosthesis. A control group consisted of 36 patients (47 hips) who underwent total hip arthroplasty due to degenerative hip dysplasia.



In the previously operated patients the centre of rotation of the hip was on the average placed more proximally, while in the control group of patients the position of the acetabular component was closer to the anatomical one. In the group of patients after Chiari osteotomy the mean acetabular cup abduction angle rated 41.8°±9.8°, while in the control group this value was on the average higher (45.4°±8.6°).



There was a significant difference between the studied groups in relation to the distance between the acetabular component of endoprosthesis and the acetabular teardrop (t=-2.763; p=0.007). No statistically significant difference was determined in the mean value of the angle of acetabular abduction component of endoprosthesis between the studied groups of patients (t=1.878; p=0.064).



Acetabular component position of the total hip endoprosthesis was not compromised by anatomic changes of the acetabulum caused by Chiari pelvic osteotomy.
Relationship between interferon regulatory factor 4 genetic polymorphisms, measures of sun sensitivity and risk for non-Hodgkin lymphoma

Sun exposure and sensitivity, including pigmentation, are associated with risk for non-Hodgkin lymphoma (NHL). One variant in the immune regulatory factor 4 (IRF4) gene (rs12203592) is associated with pigmentation, and a different IRF4 variant (rs12211228) is associated with NHL risk. We evaluated the independent roles of these IRF4 polymorphisms and sun sensitivity in mediating NHL risk and explored whether they are confounded or modified by each other. Genotyping of tag single nucleotide polymorphisms (SNPs) in the IRF4 gene was conducted in 990 NHL cases and 828 controls from a multi-center US study. Measures of sun sensitivity and exposure were ascertained from computer-assisted personal interviews. We used logistic regression to compute odds ratios (OR) and 95% confidence intervals (CI) for NHL in relation to sun exposures, sun exposures in relation to IRF4 genotypes, and NHL in relation to sun exposures. We further assessed the effects of sun exposures in relation to IRF4 genotypes. As previously reported, we found significant associations between IRF4 rs12211228 and NHL and between hair and eye color and NHL. The IRF4 rs12203592 polymorphism (CT/TT genotype) was statistically significantly associated with eye color and particularly with hair color (ORLight Blonde = 0.24, 95% CI = 0.11–0.50, overall Chi square p = 0.0002). Analysis of joint effects between eye and hair color with the IRF4 rs12203592 SNP did not reveal statistically significant p-interactions although NHL risk did decline with lighter hair color and presence of the variant IRF4 rs12203592 allele, compared to those without a variant allele and with black/brown hair color. Our data do not statistically support a joint effect between IRF4 and sun sensitivity in mediating risk for NHL. Further evaluation of joint effects in other and larger populations is warranted.
Vitamin E supplements in asthma: a parallel group randomised placebo controlled trial.

Increased dietary vitamin E intake is associated with a reduced incidence of asthma, and combinations of antioxidant supplements including vitamin E are effective in reducing ozone induced bronchoconstriction. A study was undertaken to investigate the effect of supplementation with vitamin E for 6 weeks on bronchial hyperresponsiveness in atopic adults with asthma.



72 participants from a clinical trial register of adults with asthma were randomised to receive 500 mg natural vitamin E or matched placebo for 6 weeks in a placebo controlled, double blind parallel group clinical trial. Inclusion criteria included age 18-60 years, maintenance treatment of at least one dose of inhaled corticosteroid per day, a positive skin prick test to one of three common allergens, and bronchial hyperresponsiveness to methacholine (defined as a dose provoking a 20% fall in forced expiratory volume in 1 second (FEV(1)) (PD(20)) of 12.25 micromol). Secondary outcomes were FEV(1), forced vital capacity, mean morning and evening peak flow, symptom scores, bronchodilator use, and serum immunoglobulin E levels.



In the primary intention to treat analysis the change in PD(20) was similar in the vitamin E and placebo groups with a mean difference of +0.25 doubling doses of methacholine (95% confidence interval -0.67 to +1.16 greater with vitamin E). There was no effect of vitamin E supplementation on any other measure of asthma control, either in the intention to treat or per protocol analysis. There was also no effect of vitamin E supplementation on serum immunoglobulin levels.



Dietary supplementation with vitamin E adds no benefit to current standard treatment in adults with mild to moderate asthma.
Prognostic effect of tuberculosis on patients with occupational lung diseases

Occupational lung diseases are well recognized risk factors for tuberculosis (TB). However, little research investigated the effect of TB on the clinical course and outcome of occupational lung diseases.We conducted a 13-year observational study of a nationwide cohort to evaluate the risk and prognosis of TB among patients with occupational lung diseases in Taiwan.By using the Taiwan National Health Insurance database, occupational lung diseases cohort was identified according to diagnosis codes from 1998 to 2008 and prospectively monitored until the end of 2010, loss to follow-up, or death. Newly diagnosed TB, comorbidities, and demographic characteristics were evaluated as prognostic variables in the survival analysis of patients with occupational lung diseases using Cox proportional hazard regression models.A total of 12,787 study participants were enrolled with an average of 9.69 years of follow-up. Among them, 586 (4.58%) had newly diagnosed TB and 3180 (24.87%) died during follow-up. The incidence of TB was 473 per 100,000 person-years, and the risk of TB infection significantly increased over time. The independent risk factors for mortality included male gender (hazard ratio [HR]: 2.23, 95% confidence interval [CI]: 1.91-2.60), age (HR: 1.05, 95% CI: 1.05-1.06), TB (HR: 1.17, 95% CI: 1.01-1.37), congestive heart failure (HR: 1.44, 95% CI: 1.17-1.79), cerebrovascular disease (HR: 1.34, 95% CI: 1.15-1.57), chronic obstructive pulmonary disease (HR: 1.44, 95% CI: 1.33-1.56), and asthma (HR: 1.27, 95% CI: 1.15-1.40). In addition, patients with TB infections had worse outcomes in the survival analysis than those without TB (log-rank test P = 0.02).Despite the low prevalence of occupational lung diseases in Taiwan, patients with those diseases had a higher TB incidence than the general population did (473 vs 55 per 100,000 person-years). Furthermore, even with effective antimicrobial chemotherapy, TB infection was a prognostic factor leading to poor outcomes in the patients with occupational lung diseases. We recommend intensive medical surveillance of TB in these high-risk patients for better control of TB and improvement of occupational health in Taiwan.
Genetic associations with toxicity-related discontinuation of aromatase inhibitor therapy for breast cancer

Up to 25 % of patients discontinue adjuvant aromatase inhibitor (AI) therapy due to intolerable symptoms. Predictors of which patients will be unable to tolerate these medications have not been defined. We hypothesized that inherited variants in candidate genes are associated with treatment discontinuation because of AI-associated toxicity. We prospectively evaluated reasons for treatment discontinuation in women with hormone receptor-positive breast cancer initiating adjuvant AI through a multicenter, prospective, randomized clinical trial of exemestane versus letrozole. Using multiple genetic models, we evaluated potential associations between discontinuation of AI therapy because of toxicity and 138 variants in 24 candidate genes, selected a priori, primarily with roles in estrogen metabolism and signaling. To account for multiple comparisons, statistical significance was defined as p < 0.00036. Of the 467 enrolled patients with available germline DNA, 152 (33 %) discontinued AI therapy because of toxicity. Using a recessive statistical model, an intronic variant in ESR1 (rs9322336) was associated with increased risk of musculoskeletal toxicity-related exemestane discontinuation [HR 5.0 (95 % CI 2.1–11.8), p < 0.0002]. An inherited variant potentially affecting estrogen signaling may be associated with exemestane-associated toxicity, which could partially account for intra-patient differences in AI tolerability. Validation of this finding is required.