nils-herrmann/clean_scirepeval huggingface dataset:
The usage of biological DMARDs and clinical remission of rheumatoid arthritis in China: a real-world large scale study

The aims of this study are to characterize the biological disease-modifying antirheumatic drug (bDMARD) usage patterns in real-life and examine the remission rate of rheumatoid arthritis (RA) patients receiving bDMARDs in routine clinical practice in China. Consenting RA patients (≥18 years) from 15 teaching hospitals and receiving marketed bDMARDs were included. In total, 802 patients (81.3 % women, 49.0 ± 13.9 years) were included; 89.5 % were receiving a combination of bDMARDs and conventional synthetic DMARDs (csDMARDS), whereas 10.5 % were receiving bDMARD monotherapy. Etanercept (including Enbrel® and local brand Yi Sai Pu® and Qiangke®), tocilizumab, adalimumab, and infliximab were used by 66.6 %, 17.0 %, 7.5 %, and 6.6 % patients, respectively. Etanercept was used at a mean weekly dose of 38.2 ± 15.6 mg for 25.5 ± 47.0 weeks and tocilizumab at 94.5 ± 21.9 mg for 4.7 ± 7.5 weeks. Overall rate of remission was 12.6 %, 5.4 % , and 3.5 % based on DAS28, CDAI, and SDAI scores, respectively. Compared with patients receiving bDMARDs for <3 months, those receiving bDMARDs for ≥3 months exhibited significantly lower DAS28 scores (p < 0.0001), and a significantly higher proportion of patients who received bDMARDs for ≥12 months achieved the treatment goal (remission or low disease activity, 62.5 % vs. 18.3 %, p < 0.0001). Patients receiving combination therapy with csDMARDs exhibited lower DAS28 scores than patients receiving bDMARD monotherapy (4.3 vs. 4.8, p = 0.011). This large-scale real-world study showed that bDMARD usage patterns in routine clinical practice in China were in accordance with international guidelines for RA management despite the short treatment duration. Longer duration of bDMARD usage and combination therapy showed a favored outcome of RA.
Phase II trial of neoadjuvant weekly nanoparticle albumin-bound paclitaxel, carboplatin, and biweekly bevacizumab therapy in women with clinical stage II or III HER2-negative breast cancer.

We hypothesized that adding bevacizumab to neoadjuvant chemotherapy (NCT) with nab-P and carboplatin would increase the rates of pCR in BC patients and that early changes in tumor vascularity imaged by dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) would predict pCR.



Thirty-three women with clinical stage II or III HER2-negative BC received nab-P 100 mg/m2 and carboplatin area under the curve = 2 on days 1, 8, and 15 in combination with bevacizumab 10 mg/kg on days 1 and 15 administered every 28 days.



Six patients (18%) achieved pCR, all pCRs occurred in triple-negative BC (TNBC) (pCR = 50% for TNBC). At the end of cycle 2, the changes in relative angiogenic volume were significantly different between responders and nonresponders (P = .001). The major toxicity of this NCT was myelosuppression.



NCT with weekly nab-P, carboplatin, and biweekly bevacizumab resulted in a pCR rate that was neither superior to the historical data with anthracycline- or taxane-containing NCT nor to carboplatin and taxane combinations in patients with HER2-negative BC. In patients with TNBC, the observed pCR rate was 50%. The early changes in the relative angiogenic volume imaged by DCE-MRI could predict pCR.
Cognitive effects of topiramate revealed by standardised low-resolution brain electromagnetic tomography (sLORETA) of event-related potentials

To evaluate the effect of topiramate (TPM) on event-related potentials (ERPs) in patients with epilepsy.



Neuropsychological tests and ERP study using auditory oddball paradigm were conducted before and after treatment with TPM in drug-naive epilepsy patients. To detect target brain regions in which ERP changed during the cognitive task, cortical current densities of ERP components were analysed using standardised low-resolution electromagnetic tomography (sLORETA).



Neuropsychological tests (n=18 patients) showed that TPM significantly decreased the score in digit span, Corsi block and Controlled Oral Word Association word fluency. Repeated-measures analysis of variance of ERP data (n=13 patients) revealed that P2 amplitude was significantly increased at Fz electrode following treatment with TPM. Statistical non-parametric map of sLORETA between pre- and post-TPM ERPs revealed that current density of P200 component was significantly reduced by TPM in bilateral parieto-occipital, temporolimbic and dorsolateral right prefrontal regions.



Our findings suggest that TPM affects selective brain regions which may be related to cognitive side effects.



Source localisation of ERPs can be helpful in identifying target brain regions for the cognitive side effects of anti-epileptic drugs.
Robotic liver surgery: results for 70 resections.

Robotic surgery is gaining popularity for digestive surgery; however, its use for liver surgery is reported scarcely. This article reviews a surgeon's experience with the use of robotic surgery for liver resections.



From March 2002 to March 2009, 70 robotic liver resections were performed at 2 different centers by a single surgeon. The surgical procedure and postoperative outcome data were reviewed retrospectively.



Malignant tumors were indications for resections in 42 (60%) patients, whereas benign tumors were indications in 28 (40%) patients. The median age was 60 years (range, 21-84) and 57% of patients were female. Major liver resections (≥ 3 liver segments) were performed in 27 (38.5%) patients. There were 4 conversions to open surgery (5.7%). The median operative time for a major resection was 313 min (range, 220-480) and 198 min (range, 90-459) for minor resection. The median blood loss was 150 mL (range, 20-1,800) for minor resection and 300 mL (range, 100-2,000) for major resection. The mortality rate was 0%, and the overall rate of complications was 21%. Major morbidity occurred in 4 patients in the major hepatectomies group (14.8%) and in 4 patients in the minor hepatectomies group (9.3%). All complications were managed conservatively and none required reoperation.



This preliminary experience shows that robotic surgery can be used safely for liver resections with a limited conversion rate, blood loss, and postoperative morbidity. Robotics offers a new technical option for minimally invasive liver surgery.
End-stage renal disease status and critical illness in the elderly.

Elderly patients (> 65 years old) are a rapidly growing demographic in the ESRD and intensive care unit (ICU) populations, yet the effect of ESRD status on critical illness in elderly patients remains unknown. Reliable estimates of prognosis would help to inform care and management of this frail and vulnerable population.



The effect of ESRD status on survival and readmission rates was examined in a retrospective cohort of 14,650 elderly patients (>65 years old) admitted to 11 ICUs in Winnipeg, Manitoba, Canada between 2000 and 2006. Logistic regression models were used to adjust odds of mortality and readmission to ICU for baseline case mix and illness severity.



Elderly ESRD patients had twofold higher crude in-hospital mortality (22% versus 13%, P < 0.0001) and readmission rate (6.4 versus 2.7%, P = 0.001). After adjustment for illness severity alone or illness severity and case mix, the odds ratio for mortality decreased to 0.85 (95% CI: 0.57 to 1.25) and 0.82 (95% CI: 0.55 to 1.23), respectively. In contrast, ESRD status remained significantly associated with readmission to ICU after adjustment for other risk factors (OR 2.06 [95% CI: 1.32, 3.22]).



Illness severity on admission, rather than ESRD status per se, appears to be the main driver of in-hospital mortality in elderly patients. However, ESRD status is an independent risk factor for early and late readmission, suggesting that this population might benefit from alternative strategies for ICU discharge.
Assessment of laparoscopic stomach preserving surgery with sentinel basin dissection versus standard gastrectomy with lymphadenectomy in early gastric cancer–A multicenter randomized phase III clinical trial (SENORITA trial) protocol

Along with the marked increase in early gastric cancer (EGC) in the Eastern countries, there has been an effort to adopt the sentinel node concept in EGC to preserve gastric function and reduce the occurrence of postoperative complications. Based on promising results from a previous quality control study, this prospective multicenter randomized controlled phase III clinical trial aims to elucidate the oncologic safety of laparoscopic stomach-preserving surgery with sentinel basin dissection (SBD) compared to a standard laparoscopic gastrectomy. This trial is an investigator-initiated, open-label, multicenter randomized controlled phase III trial with a non-inferiority design. Patients diagnosed with a single lesion of clinical stage T1N0M0 gastric adenocarcinoma, with a diameter of 3 cm or less are eligible for the present study. A total of 580 patients (290 per group) will be randomized to either laparoscopic stomach-preserving surgery with SBD or standard surgery. The primary end-point is 3-year disease-free survival (DFS) and the secondary endpoints include postoperative morbidity and mortality, quality of life, 5-year DFS, and overall survival. Qualified investigators who completed the prior quality control study are exclusively allowed to participate in this phase III clinical trial. The proposed trial is expected to verify whether laparoscopic stomach-preserving surgery with SBD achieves similar oncologic outcomes and improved quality of life compared to a standard gastrectomy in EGC patients.
Measurement properties of the Flu-Like Symptom Index from the Hepatitis Physical Symptom Severity Diary

Chronic Hepatitis C (CHC) Virus infection is a serious health issue in the US. Standard treatment involves peginterferon alpha and ribavirin, often associated with adverse side effects including flu-like symptoms. These adverse effects are common reasons for the discontinuation of treatment and therefore represent a major obstacle in the effective treatment of CHC. The Hepatitis Physical Symptom Severity Diary, a newly developed patient-reported outcome measure for assessing physical symptoms in CHC patients, was recently developed. It contains four questions addressing flu-like symptoms [the Flu-Like Symptom Index (FLSI)]. Measurement properties of the FLSI in CHC patients were assessed using data from two randomized clinical trials. Exploratory factor analysis using data from baseline and the last visit while on treatment supported a single-factor solution for the FLSI. Internal reliability and test–retest reliability are acceptable (Cronbach’s alpha range 0.73–0.81; intraclass correlation coefficient range 0.85–0.97), and correspondence to several similar constructs was acceptable. The FLSI score was higher among those with investigator-reported flu-like symptoms (mean = 4.1) versus those without (1.4), although not statistically significant (p = 0.12). Responsiveness of the FLSI was moderate, as measured by standardized effect sizes and response means, and the minimum important difference (MID) was estimated at 2.5–3.0 points. While additional research should be conducted to evaluate validity with more closely related constructs and to utilize anchor-based methods for estimating the MID, data suggest that the FLSI has acceptable measurement properties and can be an effective tool in assessing flu-like symptoms in CHC patients.
Validation of an UPLC-MS/MS method for quantitative analysis of raltegravir in human plasma samples.

An ultra-performance liquid chromatography-tandem mass spectrometry method was developed for the quantification of raltegravir (RTG) plasma concentrations in samples from HIV patients treated with the drug.



Plasma samples were extracted by liquid-liquid extraction followed by evaporation to dryness and reconstitution in mobile phase. The chromatographic separation was carried out on an AQUITY UPLC C18 column with an isocratic mobile phase consisting of water containing 0.1% formic acid and acetonitrile containing 0.1% formic acid (50:50 vol/vol). The detection was performed on a triple quadrupole tandem mass spectrometer using multi-reaction monitoring via electrospray ionization source with positive ionization mode.



Under these conditions, a single chromatographic run could be completed within 1 minute. The method was validated by estimating the precision and the accuracy for inter- and intra-day analysis in the concentration range of 5-2560 ng/mL. The method was linear over the investigated range with all the correlation coefficients, r, greater than 0.995 on 5 replicates. The intra- and inter-day precision (percentage of coefficient of variation) ranged from 2.4% to 11.2%, and the inaccuracy (percent of relative standard deviation) ranged from 2.5% to 12.9%. No significant matrix effect was observed. The mean recovery value of RTG was 80%.



This rapid and sensitive method was validated and could be applied to pharmacokinetic studies for the determination of RTG concentrations in human plasma samples.
Diuretic response in patients with acute decompensated heart failure: characteristics and clinical outcome—an analysis from RELAX-AHF

We studied the characteristics and clinical outcome related to diuretic response and the effects of serelaxin in patients hospitalized for acute heart failure (AHF).



RELAX-AHF was a double-blind, placebo-controlled trial, enrolling 1161 patients admitted to hospital for AHF who were randomized to 48 h i.v infusions of placebo or serelaxin (30 µg/kg per day) within 16 h from presentation. Diuretic response was defined as Δ weight kg/[(total i.v. dose)/40 mg] + [(total oral dose)/80 mg)] furosemide (or equivalent loop diuretic dose) up to day 5. Median diuretic response was -0.42 (-1.00, -0.14) kg/40 mg. A poor diuretic response was independently associated with Western-like region (Western Europe, North America, Israel, and Poland), lower diastolic blood pressure, the absence of oedema, higher blood urea nitrogen, and lower levels of aspartate aminotransferase and potassium (all P < 0.01). Randomization to serelaxin was associated with lower doses of i.v. loop diuretics and slightly less weight loss, resulting in a neutral effect on diuretic response. Worse diuretic response was independently associated both with less relief of dyspnoea, measured with a visual analogue scale (VAS) at day 5 (primary endpoint; P = 0.0002), and with a higher risk of cardiovascular death or rehospitalization for heart failure or renal failure through day 60 (secondary endpoint, P < 0.0001), but not with increased 180-day cardiovascular mortality (P = 0.507).



In patients hospitalized for AHF, a poor diuretic response was associated with a poor in-hospital and early post-discharge clinical outcome. Serelaxin had a neutral effect on diuretic response.
PlA polymorphism of the glycoprotein IIIa and efficacy of reperfusion therapy in patients with acute myocardial infarction.

The Pl(A) polymorphism of the platelet glycoprotein IIIa gene is associated with altered platelet function and response to antiplatelet drugs. We sought to assess whether the Pl(A) polymorphism influences myocardial salvage achieved by reperfusion therapy in patients with acute myocardial infarction. We analyzed 292 patients enrolled in 2 randomized trials that compared stenting plus abciximab with thrombolysis (alteplase alone or alteplase plus abciximab) in acute myocardial infarction. Patients were genotyped for the Pl (A) polymorphism using polymerase chain reaction with fluorogenic probes. Technetium-99m sestamibi was injected before and 1-2 weeks after reperfusion treatment. The scintigrams enabled the calculation of the initial perfusion defect, final infarct size, and the proportion of initial defect salvaged by reperfusion (salvage index). Clinical follow-up was done up to 18 months after primary treatment. The genotype distribution was as follows: Pl (A2/A2) in 3.4%, Pl (A1/A2) in 24.7% and Pl (A1/A1) in 71.9% of patients. There were no significant differences between Pl( A2) allele carriers and Pl(A1/A1) patients in salvage index (0.4+/-0.50 vs. 0.4+/-0.43, respectively, P=0.48), final infarct size (16.8+/-20.8% vs. 18.4+/-19.1% of left ventricle, respectively, P=0.46) as well as 18-month mortality (8.5% vs.7.1%, respectively, P=0.69). The lack of relationship between Pl(A2) allele and myocardial salvage was observed for both reperfusion strategies, stenting and thrombolysis. Thus, these findings show that the functional Pl(A) polymorphism of platelet glycoprotein IIIa has no influence on the degree of myocardial salvage achieved by reperfusion therapies in patients with acute myocardial infarction.
Pharmacokinetics of carboplatin administered with lobradimil to pediatric patients with brain tumors

To determine the pharmacokinetics of adaptively dosed carboplatin when administered in combination with the bradykinin agonist, lobradimil (RMP-7, Cereport), to pediatric patients with brain tumors. Carboplatin pharmacokinetic studies were performed on 21 of 25 children with primary brain tumors who received carboplatin and lobradimil on two consecutive days every 28 days in a phase I dose-escalation trial of lobradimil. Carboplatin was adaptively dosed, based on the radioisotopic glomerular filtration rate (GFR) to achieve a target plasma area under the concentration vs time curve (AUC) of 3.5 mg⋅min/ml per dose ×2 (2.5 mg⋅min/ml per dose ×2 in patients with prior craniospinal radiation or myeloablative chemotherapy). The adaptive dosing formula was: carboplatin dose (mg/m2)=target AUC (mg⋅min/ml) × [0.93 × GFR (ml/min/m2)+15]. Carboplatin was infused over 60 min (n=15) or 15 min (n=6). The 10-min lobradimil infusion (100–600 ng/kg ideal body weight) began 5 min before the end of the carboplatin infusion. Frequent blood samples were drawn over 24 h after the first dose of carboplatin/lobradimil. Ultrafilterable platinum was measured by atomic absorption spectroscopy, and the AUC of ultrafilterable platinum was derived using the linear trapezoidal rule and extrapolated to infinity. The median GFR was 65 ml/min/m2 (range 38–95 ml/min/m2) and the median carboplatin doses for the 2.5 and 3.5 mg min/ml target AUCs were 154 and 276 mg/m2/day (124–235 and 179–360 mg/m2/day), respectively. The measured carboplatin AUC exceeded the target AUC in all 21 patients by a median of 35% (range 0.2–131%). The median carboplatin AUCs at the 2.5 and 3.5 mg⋅min/ml target AUCs were 3.4 and 4.8 mg⋅min/ml (2.51–5.8 and 3.9–7.7 mg⋅min/ml), respectively. Carboplatin clearance was lower than values previously reported in children and correlated poorly with GFR (r 2=0.14). Adaptive dosing of carboplatin based on GFR overestimated the dose required to achieve the target carboplatin AUC in pediatric patients with brain tumors treated with concurrent lobradimil. The degree to which the measured carboplatin AUC exceeded the target AUC appeared to be greater at higher doses of lobradimil, suggesting that the failure of the adaptive dosing method was related to an unexpected pharmacokinetic drug interaction.
4-year clinical outcomes and predictors of repeat revascularization in patients treated with new-generation drug-eluting stents: a report from the RESOLUTE All-Comers trial (A Randomized Comparison of a Zotarolimus-Eluting Stent With an Everolimus-Eluting Stent for Percutaneous Coronary Intervention

The aim of the study was to investigate 4-year outcomes and predictors of repeat revascularization in patients treated with the Resolute zotarolimus-eluting stent (R-ZES) (Medtronic, Minneapolis, Minnesota) and XIENCE V everolimus-eluting stent (EES) (Abbott Vascular, Abbott Park, Illinois) in the RESOLUTE (A Randomized Comparison of a Zotarolimus-Eluting Stent With an Everolimus-Eluting Stent for Percutaneous Coronary Intervention) All-Comers trial.



Data on long-term outcomes of new-generation drug-eluting stents are limited, and predictors of repeat revascularization due to restenosis and/or progression of disease are largely unknown.



Patients were randomly assigned to treatment with the R-ZES (n = 1,140) or the EES (n = 1,152). We assessed pre-specified safety and efficacy outcomes at 4 years including target lesion failure and stent thrombosis. Predictors of revascularization at 4 years were identified by Cox regression analysis.



At 4 years, the rates of target lesion failure (15.2% vs. 14.6%, p = 0.68), cardiac death (5.4% vs. 4.7%, p = 0.44), and target vessel myocardial infarction (5.3% vs. 5.4%, p = 1.00), clinically-indicated target lesion revascularization (TLR) (7.0% vs. 6.5%, p = 0.62), and definite/probable stent thrombosis (2.3% vs. 1.6%, p = 0.23) were similar with the R-ZES and EES. Independent predictors of TLR were age, insulin-treated diabetes, SYNTAX (Synergy between PCI with Taxus and Cardiac Surgery) score, treatment of saphenous vein grafts, ostial lesions, and in-stent restenosis. Independent predictors of any revascularization were age, diabetes, previous percutaneous coronary intervention, absence of ST-segment elevation myocardial infarction, smaller reference vessel diameter, SYNTAX score, and treatment of left anterior descending, right coronary artery, saphenous vein grafts, ostial lesions, or in-stent restenosis.



R-ZES and EES demonstrated similar safety and efficacy throughout 4 years. TLR represented less than one-half of all repeat revascularization procedures. Patient- and lesion-related factors predicting the risk of TLR and any revascularization showed considerable overlap.