nils-herrmann/clean_scirepeval huggingface dataset:
Treatment strategies and long-term results in paediatric patients treated in four consecutive AML-BFM trials

A total of 1111 children with acute myeloblastic leukaemia (AML) were treated in four consecutive Berlin–Frankfurt–Münster (BFM) studies from 1978 to 1998. The first cooperative trial AML-BFM 78 established intensive chemotherapy with seven drugs, CNS irradiation and 2-year maintenance, achieving a long-term survival (overall survival (OS)) of 40%. Induction intensification in AML-BFM 83 resulted in significant improvement of disease-free survival (DFS). The risk of haemorrhage, especially in children with hyperleukocytosis, proved the high relevance of supportive care. In AML-BFM 87, the benefit of CNS irradiation in preventing CNS/systemic relapses was demonstrated. In AML-BFM 93, the introduction of idarubicin during first induction followed by intensification with HAM increased the 5-year EFS, DFS and OS to 50±2, 61±3 and 57±2%, respectively. Stem cell transplantation (SCT), as applied in high-risk patients with a matched related donor, did not significantly improve the outcome compared to chemotherapy alone. In spite of treatment intensification, the therapy-related death rate decreased from trial to trial, mainly during induction. The future aim is to reduce long-term sequelae, especially cardiotoxicity, by administration of less cardiotoxic drugs, and toxicity of SCT by risk-adapted indications. The AML-BFM studies performed in three European countries with >70 cooperating centres have significantly improved the outcome in AML children; nevertheless, increasing experience with these intensive treatment regimens is of fundamental importance to reduce fatal complications.
Tumour markers for prediction of survival and monitoring of remission in small cell lung cancer.

Levels of the tumour markers neurone specific enolase (NSE), lactate dehydrogenase (LDH), chromogranin A (ChrA) and carcinoembryonic antigen (CEA) were measured in serum taken at presentation and during treatment, remission and relapse from 154 patients who received chemotherapy for small cell lung cancer at a single centre over a 6 year period. At presentation NSE was the most frequently elevated marker, being raised in 81% of patients and significantly higher in extensive as opposed to limited disease, as were LDH and ChrA. The response rate to therapy was best correlated with presentation level of ChrA, being 79% for those whose levels were within twice the upper limit of normal and 51% above (P < 0.01). Multivariate regression analysis showed NSE, performance status and albumin at presentation to be the best independent predictors of survival. Patients with NSE below twice the upper limit of normal, Karnofsky performance status of 80 or above and albumin 35 g l-1 or above had a median survival of 15 months with 25% alive at 2 years, whilst those with NSE above twice normal, Karnofsky below 80 and albumin less that 35 g l-1 had all died by 8 months. Changes in marker levels during therapy were of low predictive value for outcome although the finding of rising NSE during chemotherapy after an initial fall correlated with significantly reduced duration of remission. There was a strong inverse correlation between the NSE level at the time of response and duration of remission (P < 0.0001). Prediction of relapse was most reliable with ChrA, 52% of patients having rising levels before clinical evidence of disease recurrence.
A randomized, open-label trial of iron isomaltoside 1000 (Monofer®) compared with iron sucrose (Venofer®) as maintenance therapy in haemodialysis patients

Iron deficiency anaemia is common in patients with chronic kidney disease, and intravenous iron is the preferred treatment for those on haemodialysis. The aim of this trial was to compare the efficacy and safety of iron isomaltoside 1000 (Monofer®) with iron sucrose (Venofer®) in haemodialysis patients.



 or iron sucrose (Group B). Subjects in Group A were equally divided into A1 (500 mg single bolus injection) and A2 (500 mg split dose). Group B were also treated with 500 mg split dose. The primary end point was the proportion of subjects with haemoglobin (Hb) in the target range 9.5-12.5 g/dL at 6 weeks. Secondary outcome measures included haematology parameters and safety parameters.



A total of 351 subjects were enrolled. Both treatments showed similar efficacy with >82% of subjects with Hb in the target range (non-inferiority, P = 0.01). Similar results were found when comparing subgroups A1 and A2 with Group B. No statistical significant change in Hb concentration was found between any of the groups. There was a significant increase in ferritin from baseline to Weeks 1, 2 and 4 in Group A compared with Group B (Weeks 1 and 2: P < 0.001; Week 4: P = 0.002). There was a significant higher increase in reticulocyte count in Group A compared with Group B at Week 1 (P < 0.001). The frequency, type and severity of adverse events were similar.



Iron isomaltoside 1000 and iron sucrose have comparative efficacy in maintaining Hb concentrations in haemodialysis subjects and both preparations were well tolerated with a similar short-term safety profile.
Serum lipid responses to phytosterol-enriched milk in a moderate hypercholesterolemic population is not affected by apolipoprotein E polymorphism or diameter of low-density lipoprotein particles

The importance of both low-density lipoprotein cholesterol (LDLc) size and the apolipoprotein E (Apo E) in the atherogenic process is known, but there is little information with regard to the effect of phytosterols (PS) on these parameters. The aim of this study was to evaluate the influence of PS on lipid profile and LDLc size according to Apo E genotype.This was a randomized parallel trial employing 75 mild-hypercholesterolemic subjects and consisting of two 3-month intervention phases. After 3 months of receiving a standard healthy diet, subjects were divided into two intervention groups: a diet group (n=34) and a diet+PS group (n=41) that received 2 g/day of PS. Total cholesterol (TC), triacylglycerols, LDLc, high-density lipoprotein cholesterol (HDLc), non-HDLc, Apo A–I and B-100, LDLc size and Apo E genotype were determined.Patients receiving PS exhibited a significant decrease in TC (5.1%), LDLc (8.1%), non-HDLc (7.4%) and Apo B-100/Apo A–I ratio (7.7%), but these effects did not depend on Apo E genotype. No significant changes were found in lipid profile according to Apo E genotype when patients following dietary recommendations were considered as a whole population or separately. No variations in LDLc size were observed in any of the intervention groups.The results of this study show that Apo E genotype does not have an impact on the lipid response to PS as a cholesterol-lowering agent in mild-hypercholesterolemic patients. Furthermore, the evidence obtained confirms that LDLc particle size is not modified when PS are added to a standard healthy diet.
Relationship of body mass index in young adulthood and health-related quality of life two decades later: the Coronary Artery Risk Development in Young Adults study

The expanding overweight and obesity epidemic notwithstanding, little is known about their long-term effect on health-related quality of life (HRQoL). The main objective of this study was to investigate whether overweight (body mass index (BMI) 25 to <30 kg m−2) and obese (BMI ⩾30 kg m−2) young adults have poorer HRQoL 20 years later.We studied 3014 participants in the Coronary Artery Risk Development in Young Adults (CARDIA) study, a longitudinal, community-dwelling, biracial cohort from four cities. BMI was measured at baseline and 20 years later. HRQoL was assessed by the Physical Component Summary (PCS) and the Mental Component Summary (MCS) scores of the Medical Outcomes Study 12-Item Short-Form Health Survey at year 20. Higher PCS or MCS scores indicate better HRQoL.Results:Mean year 20 PCS score was 52.2 for normal weight participants at baseline, 50.3 for overweight and 46.4 for obese (P-trend <0.001). This relation persisted after adjustment for baseline demographics, general health, and physical and behavioral risk factors and after further adjustment for 20-year changes in risk factors. No association was observed for MCS scores (P-trend 0.43).Conclusion:Overweight and obesity in early adulthood are adversely associated with self-reported physical HRQoL, but not mental HRQoL 20 years later.
Factors associated with previously undiagnosed human immunodeficiency virus infection in a population of men who have sex with men and male-to-female transgender women in Lima, Peru

The aim of the study was to identify factors associated with undiagnosed human immunodeficiency virus (HIV) infection among men who have sex with men (MSM) and male-to-female transgender women in Lima, Peru.We analyzed characteristics of 378 MSM and transgender women recruited from 2 sexually transmitted infection (STI) clinics in Lima, Peru. Descriptive analyses compared: (A) HIV-uninfected, (B) previously undiagnosed HIV-infected, and (C) previously diagnosed HIV-infected participants. Multivariable logistic regression models identified: (1) correlates of previously undiagnosed HIV-infection among participants thought to be HIV-uninfected (B vs A); and (2) correlates of previously undiagnosed HIV-infection among HIV-infected participants (B vs C). Subanalysis identified correlates of frequent HIV testing among participants thought to be HIV-uninfected.Among participants, 31.0% were HIV-infected; of those, 35.0% were previously undiagnosed. Among participants thought to be HIV-uninfected (model 1), recent condomless receptive anal intercourse and last HIV test being over 1-year ago (compared to within the last 6-months) were associated with increased odds of being previously undiagnosed HIV-infected (adjusted odds ratio [aOR] = 2.43, 95% confidence interval [95%CI] = 1.10-5.36; aOR = 2.87, 95%CI = 1.10-7.53, respectively). Among HIV-infected participants (model 2), recent condomless receptive anal intercourse was again associated with previously undiagnosed HIV-infection (aOR = 2.54, 95%CI = 1.04-6.23). Achieving post-secondary education and prior syphilis infection were associated with lower odds of having previously undiagnosed HIV-infection (aOR = 0.35, 95%CI = 0.15-0.81; aOR = 0.32, 95%CI = 0.14-0.75, respectively).Reporting semiannual testing was associated with higher educational attainment, identifying as a transgender woman, or reporting a history of syphilis (aOR = 1.94, 95%CI = 1.11-3.37; aOR = 2.40, 95%CI = 1.23-4.70; aOR = 2.76, 95%CI = 1.62-4.71, respectively). Lower odds of semiannual testing were associated with recent condomless insertive anal intercourse or reporting a moderate or high self-perceived risk of acquiring HIV (aOR = 0.56, 95%CI = 0.33-0.96; aOR = 0.32, 95%CI = 0.18-0.59 and aOR = 0.43, 95%CI = 0.21-0.86, respectively).In our study, undiagnosed HIV-infection was associated with recent condomless receptive anal intercourse, infrequent HIV testing, lower education, and absence of prior syphilis diagnosis. Infrequent HIV testing was associated with lower education, not identifying as transgender, recent condomless insertive anal intercourse, absence of prior syphilis diagnosis, and higher self-perceived risk of HIV. Further efforts to decrease HIV transmission and increase HIV-serostatus awareness should be directed towards effectively promoting condom use and frequent HIV testing, integrated with STI management.
Assessment of accuracy and applicability of a portable electronic diary card spirometer for asthma treatment.

A pocked-sized turbine flowmeter and spirometer device, integrated with an electronic diary card (EDC-spirometer, Micro Medical, U.K.), was tested with a mechanical calibrator, in an outpatient clinic and in the home situation. A screen pneumotachometer was used as flow and volume reference. Ten devices were tested; interdevice variability was small with a mean variation coefficient of 1.1% for both forced expiratory volume in 1 s (FEV1) and peak expiratory flow (PEF) (SD 0.5 and 0.4, respectively) for eight settings of the calibrator. Mean difference from reference was -0.13 l (SD 0.04) for FEV1 (range 0.38-3.16) and 0.09 l s-1 (SD 0.09) for PEF (range 4.2-11.7). No significant deviation from linearity was present. Results obtained in the outpatient clinic confirmed the accuracy of FEV1 and PEF data obtained with the calibrator. However, linear regression analysis showed a mean underestimation of 0.45 l (SD of estimate 0.29) for forced vital capacity over the whole measurement range, probably due to a restricted integration time. In 10 optimally-treated chronic obstructive pulmonary disease patients in a family practice, PEF measurements were done in the home situation, both with the EDC spirometer and a mini-Wright peak flow meter. No significant differences in the diurnal variation of PEF were found. The PEF data from the mini-Wright meter were corrected for earlier reported flow-dependent systematic deviations. In the home situation, patients preferred the EDC spirometer. It is concluded that this device is applicable in the follow-up and treatment of asthma at home.
Plasma ESR 1 Mutations and the Treatment of Estrogen Receptor – Positive Advanced Breast Cancer

ESR1mutations are selected by prior aromatase inhibitor (AI) therapy in advanced breast cancer.We assessed the impact of ESR1 mutations on sensitivity to standard therapies in two phase III randomized trials that represent the development of the current standard therapy for estrogen receptor–positive advanced breast cancer.  In a prospective-retrospective analysis,weassessedESR1mutations in available archived baseline plasma from the SoFEA (Study of Faslodex Versus ExemestaneWith or Without Arimidex) trial, which compared exemestane with fulvestrant-containing regimens in patients with prior sensitivity to nonsteroidal AI and in baseline plasma from the PALOMA3 (Palbociclib Combined With Fulvestrant in Hormone Receptor–Positive HER2-Negative Metastatic Breast Cancer After Endocrine Failure) trial, which compared fulvestrant plus placebo with fulvestrant plus palbociclib in patients with progression after receiving prior endocrine therapy. ESR1 mutations were analyzed by multiplex digital polymerase chain reaction.  In SoFEA, ESR1mutations were found in 39.1% of patients (63 of 161), of whom 49.1% (27 of 55) were polyclonal, with rates of mutation detection unaffected by delays in processing of archival plasma. Patients withESR1mutationshad improvedprogression-freesurvival (PFS) after taking fulvestrant (n=45) compared with exemestane (n=18; hazard ratio [HR], 0.52; 95%CI, 0.30 to 0.92;P= .02),whereas patientswithwildtype ESR1 had similar PFS after receiving either treatment (HR, 1.07; 95% CI, 0.68 to 1.67; P = .77). In PALOMA3,ESR1mutationswere found in theplasmaof 25.3%of patients (91of 360), ofwhom28.6% (26 of 91) were polyclonal, with mutations associated with acquired resistance to prior AI. Fulvestrant plus palbociclib improved PFS compared with fulvestrant plus placebo in both ESR1mutant (HR, 0.43; 95% CI, 0.25 to 0.74; P = .002) and ESR1 wild-type patients (HR, 0.49; 95% CI, 0.35 to 0.70; P , .001).  ESR1 mutation analysis in plasma after progression after prior AI therapy may help direct choice of further endocrine-based therapy. Additional confirmatory studies are required.
Monitoring bone strontium intake in osteoporotic females self-supplementing with strontium citrate with a novel in-vivo X-ray fluorescence based diagnostic tool.

Ten female volunteers were recruited as part of the Ryerson and McMaster University Strontium (Sr) in Bone Research Study to have their bone Sr levels measured as they self-supplemented with Sr supplements of their choice. Of the ten volunteers, nine were suffering from osteopenia and/or osteoporosis. Non-invasive bone Sr measurements were performed using an in vivo x-ray fluorescence (IVXRF) I-125 based system. Thirty minute measurements were taken at the finger and ankle, representing primarily cortical and trabecular bone, respectively. For analysis, the 14.2keV Sr K-alpha peak normalized to the Coherent peak at 35.5keV was used. Baseline readings, representing natural bone Sr levels were acquired since all volunteers had no previous intake of Sr based supplements or medications. Once Sr supplements were started, a 24h reading was taken, followed by frequent measurements ranging from weekly, biweekly to monthly. The longest volunteer participation was 1535days. The mean baseline Sr signal observed for the group was 0.42±0.13 and 0.39±0.07 for the finger and ankle, respectively. After 24h, the mean Sr signal rose to 1.43±1.12 and 1.17±0.51, for the finger and ankle, respectively, representing a statistically significant increase (p=0.0043 & p=0.000613). Bone Sr levels continued to increase throughout the length of the study. However the Sr signal varied widely between the individuals such that after three years, the highest Sr signal observed was 28.15±0.86 for the finger and 26.47±1.22 for the ankle in one volunteer compared to 3.15±0.15 and 4.46±0.36, for the finger and ankle, respectively in another. Furthermore, while it was previously reported by our group, that finger bone Sr levels may plateau within two years, these results suggest otherwise, indicating that bone Sr levels will continue to rise at both bone sites even after 4years of Sr intake.
Sestamibi and FDG-PET scans to support diagnosis of jaw osteonecrosis

Osteonecrosis of the maxillary or mandibular bone is an infrequent but often severe event occurring in patients who undergo prolonged treatment with bisphosphonates. Histology is in some cases mandatory to differentiate it from neoplastic osteolysis, but a biopsy can further contribute to bone damage. Functional imaging obtained by a tracer that shows oncotropic properties, such as Tc99m-sestamibi, in comparison to a non-tumor-specific substance such as FDG-PET, can support the differential diagnosis, thus avoiding invasive procedures. Four patients affected by multiple myeloma and jaw osteonecrosis were prospectively evaluated by sestamibi and FDG-PET scans. Local diagnosis was performed by clinical, radiological and, in some cases, histological evaluations. Each patient was studied by Tc99m-sestamibi, performed by planar anterior and posterior whole-body scans and SPECT of the head and neck, and by PET/CT. Two nuclear medicine physicians, unaware of the final diagnosis, reviewed the images. No sestamibi uptake was evident in the four patients with jaw osteonecrosis, while FDG-PET/CT showed focal uptake in all of them. Our study suggests that the combined use of sestamibi scintigraphy and FDG-PET/CT could support the clinical diagnosis of oral osteonecrosis avoiding the risks of a surgical biopsy. Studies on higher number of patients are necessary to validate these preliminary observations.
Homoarginine and mortality in an older population: the Hoorn study.

Homoarginine is an amino acid that may be involved in nitric oxide and energy metabolism. Previous studies in patient populations showed that low homoarginine levels indicate an increased risk of mortality and cardiovascular disease. We evaluated whether low plasma levels of homoarginine are associated with elevated, overall and cause-specific mortality.



The Hoorn study is a population-based study among older men and women. We calculated Cox proportional hazard ratios (HRs) for overall and cause-specific mortality according to sex-specific homoarginine quartiles.



We included 606 study participants (51·3% women; 70·0 ± 6·6 years). Homoarginine concentrations were higher in men (1·63 ± 0·51 μM), compared with women (1·30 ± 0·44 μM; P < 0·001). After a median follow-up time of 7·8 years, 112 study participants died, including 31 deaths due to cardiovascular diseases and 30 due to cancer. Associations between homoarginine levels and mortality showed a threshold effect with a significant risk increase from the second to the first quartile. Compared with the upper three quartiles, the age-, sex- and BMI-adjusted HR (with 95% CI) in the first quartile was 2·26 (1·52-3·32) for overall mortality, 4·20 (2·03-8·69) for cardiovascular mortality and 1·25 (0·55-2·85) for cancer mortality. These associations remained materially unchanged after multivariate adjustments.



Low plasma concentrations of homoarginine are a risk marker for overall mortality and especially for cardiovascular mortality in the older general population. Further studies are warranted to elucidate the underlying pathophysiological mechanisms.
Atrioventricular delay programming and the benefit of cardiac resynchronization therapy in MADIT-CRT.

The optimal atrioventricular pacing delay (AVD) in cardiac resynchronization therapy (CRT) remains to be determined.



To determine whether programming CRT devices to short AVD (S-AVD) will improve clinical response secondary to greater reductions in dyssynchrony.



The study population comprised 1235 patients with left bundle branch block enrolled in Multicenter Automatic Defibrillator Implantation Trial in Cardiac Resynchronization Therapy (MADIT-CRT). We assessed the relationship between AVD and outcomes. Patients programmed to S-AVD (median value of <120 ms; n = 337) vs long AVD (L-AVD; ≥120 ms; n = 390) were assessed for the end points of heart failure (HF) or death, death alone, and echocardiographic response to the CRT at 1-year follow-up. Outcomes were also compared to the left bundle branch block implantable cardioverter-defibrillator-only group (n = 508).



Multivariate analysis showed that patients programmed to S-AVD experienced a significant 33% (hazard ratio [HR] 0.67; 95% confidence interval [CI] 0.44-0.85; P = .037) reduction in the risk of HF or death and a 47% (HR 0.53; 95% CI 0.29-0.94; P = .031) reduction in death alone as compared with those programmed to L-AVD. Patients with CRT-programmed S-AVD and L-AVD experienced 63% (HR 0.37; 95% CI 0.26-0.53; P < .001) and 46% (HR 0.54; 95% CI 0.31-0.96; P < .001) reduction, respectively, in the risk of HF or death compared to patients with implantable cardioverter-defibrillator alone. At 1 year of follow-up, S-AVD vs L-AVD was associated with a greater reduction in left ventricular end-systolic volume (34.2% vs 30.8%; P = .002) along with a significantly greater improvement in dyssynchrony (22.3% vs 9.4%; P = .036).



Our findings indicate that in MADIT-CRT programming, the CRT AVD <120 ms was associated with a greater clinical and echocardiographic response to CRT.