nils-herrmann/clean_scirepeval huggingface dataset:
Fontolizumab, a humanised anti-interferon gamma antibody, demonstrates safety and clinical activity in patients with moderate to severe Crohn's disease.

Interferon gamma is a potent proinflammatory cytokine implicated in the inflammation of Crohn's disease (CD). We evaluated the safety and efficacy of fontolizumab, a humanised anti-interferon gamma antibody, in patients with moderate to severe CD.



A total of 133 patients with Crohn's disease activity index (CDAI) scores between 250 and 450, inclusive, were randomised to receive placebo or fontolizumab 4 or 10 mg/kg. Forty two patients received one dose and 91 patients received two doses on days 0 and 28. Investigators and patients were unaware of assignment. Study end points were safety, clinical response (decrease in CDAI of 100 points or more), and remission (CDAI < or =150).



There was no statistically significant difference in the primary end point of the study (clinical response) between the fontolizumab and placebo groups after a single dose at day 28. However, patients receiving two doses of fontolizumab demonstrated doubling in response rate at day 56 compared with placebo: 32% (9/28) versus 69% (22/32, p = 0.02) and 67% (21/31, p = 0.03) for the placebo, and 4 and 10 mg/kg fontolizumab groups, respectively. Stratification according to elevated baseline C reactive protein levels resulted in a decreased placebo response and pronounced differences in clinical benefit. Two grade 3 adverse events were reported and were considered to be related to CD. One death (during sleep) and one serious adverse event (an elective hospitalisation) occurred, both considered unrelated.



Treating active CD with fontolizumab was well tolerated and resulted in increased rates of clinical response and remission compared with placebo.
Enhancing the Prediction of 30-Day Readmission After Percutaneous Coronary Intervention Using Data Extracted by Querying of the Electronic Health Record.

Early readmission after percutaneous coronary intervention is an important quality metric, but prediction models from registry data have only moderate discrimination. We aimed to improve ability to predict 30-day readmission after percutaneous coronary intervention from a previously validated registry-based model.



We matched readmitted to non-readmitted patients in a 1:2 ratio by risk of readmission, and extracted unstructured and unconventional structured data from the electronic medical record, including need for medical interpretation, albumin level, medical nonadherence, previous number of emergency department visits, atrial fibrillation/flutter, syncope/presyncope, end-stage liver disease, malignancy, and anxiety. We assessed differences in rates of these conditions between cases/controls, and estimated their independent association with 30-day readmission using logistic regression conditional on matched groups. Among 9288 percutaneous coronary interventions, we matched 888 readmitted with 1776 non-readmitted patients. In univariate analysis, cases and controls were significantly different with respect to interpreter (7.9% for cases and 5.3% for controls; P=0.009), emergency department visits (1.12 for cases and 0.77 for controls; P<0.001), homelessness (3.2% for cases and 1.6% for controls; P=0.007), anticoagulation (33.9% for cases and 22.1% for controls; P<0.001), atrial fibrillation/flutter (32.7% for cases and 28.9% for controls; P=0.045), presyncope/syncope (27.8% for cases and 21.3% for controls; P<0.001), and anxiety (69.4% for cases and 62.4% for controls; P<0.001). Anticoagulation, emergency department visits, and anxiety were independently associated with readmission.



Patient characteristics derived from review of the electronic health record can be used to refine risk prediction for hospital readmission after percutaneous coronary intervention.
Lower-leg growth rates in children with asthma during treatment with ciclesonide and fluticasone propionate.

Measurement of short-term lower-leg growth rate in children by knemometry has become established as an integral part of the available measures of systemic activity of inhaled corticosteroids (ICS) in children. The aim of this study was to compare the effects of the novel ICS ciclesonide (CIC) and the ICS fluticasone propionate (FP) on lower-leg growth rate and hypothalamic-pituitary-adrenal-axis function in children with mild asthma. In a double-blind, placebo-controlled, three-period crossover study, 28 children, aged 6-12 yr, sequentially received daily doses of CIC 320 μg, FP 375 μg (330 μg ex-actuator) and placebo via a spacer in a randomized order. Each 2-wk treatment period was followed by a 2-wk washout period. Knemometry was performed at the beginning and end of each treatment period. Cortisol levels in 12-h overnight urine were measured at the end of each treatment period. No statistically significant differences were seen in lower-leg growth rates between CIC (0.30 mm/wk) and placebo (0.43 mm/wk) treatments. Lower-leg growth rate during FP treatment (0.08 mm/wk) was significantly reduced compared with both placebo [least squares (LS) mean: -0.35 (95% CI: -0.53, -0.18; p = 0.0002)] and CIC [LS mean: -0.23 (95% CI: -0.05, -0.40; p = 0.0137)]. Cortisol levels in 12-h overnight urine were significantly lower in the FP group when compared with CIC (p < 0.05); however, there were no statistically significant differences between each of the active treatments and placebo. CIC had no significant effect on lower-leg growth rate in children aged 6-12 yr with mild asthma. In contrast, a similar dose of FP significantly reduced lower-leg growth rate compared with placebo and CIC.
Pharmacokinetics, prandial glucose control, and safety of insulin glulisine in children and adolescents with type 1 diabetes.

The aim of this study was to investigate the pharmacokinetics, postprandial blood glucose excursions, and safety of insulin glulisine as compared with regular human insulin (RHI), both administered immediately before meals in pediatric patients with type 1 diabetes.



A total of 10 children (aged 5-11 years) and 10 adolescents (aged 12-17 years) were enrolled in a randomized, single-center, single-dose, double-blind, cross-over study. The blood glucose of fasting patients was stabilized with intravenous insulin, following which patients received 0.15 IU/kg of subcutaneously injected insulin glulisine or RHI 2 min before a weight-adjusted standardized liquid meal.



For insulin glulisine versus RHI, maximum insulin concentrations (58 vs. 33 microIU/ml, P < 0.05) and initial insulin concentrations (insulin [area under the curve] AUC(0-2h) 5,232 vs. 2,994 microIU.min(-1).ml(-1), P < 0.05; data are geometric means) were higher after insulin glulisine than RHI. Both time to maximum insulin concentration (54 vs. 66 min) and mean residence time (88 vs. 137 min, P < 0.05) were shorter with insulin glulisine versus RHI. Postprandial glucose excursions after insulin glulisine were lower than after RHI (glucose AUC(0-6h) 641 vs. 801 mg.h(-1).dl(-1), P < 0.05). The pharmacokinetic profile for insulin glulisine was similar for children and adolescents, whereas the pharmacokinetic profile for RHI demonstrated a 64% higher concentration in adolescents. Insulin glulisine was safe and well tolerated.



The rapid-acting properties of insulin glulisine that have been previously demonstrated in adults are also observed in children and adolescents with type 1 diabetes. Further, these initial data indicate that insulin glulisine is safe and well tolerated in this patient population.
Determining asthma treatment by monitoring sputum cell counts: effect on exacerbations.

One important goal of asthma treatment is to reduce exacerbations. The current authors investigated if the use of sputum cell counts to guide treatment would achieve this goal. A total of 117 adults with asthma were entered into a multicentre, randomised, parallel group-effectiveness study for two treatment strategies over a 2-yr period. In one strategy (the clinical strategy: CS) treatment was based on symptoms and spirometry. In the other (the sputum strategy: SS) sputum cell counts were used to guide corticosteroid therapy to keep eosinophils<or=2%; symptoms and spirometry were used to identify clinical control, exacerbations and other treatments. Patients were blind to sputum cell counts in both strategies and physicians were blind in the CS, thus removing bias. First, the minimum treatment to maintain control was identified in 107 patients (Phase 1) and then this treatment was continued (Phase 2) for the remaining of the 2 yrs. The primary outcomes were the relative risk reduction for the occurrence of the first exacerbation in Phase 2 and the length of time without exacerbation. The current authors also examined the type and severity of exacerbations and the cumulative dose of inhaled steroid needed. The duration and number of exacerbations in Phase 1 were similar in both groups. In Phase 2 there were a 126 exacerbations of which 79 occurred in the CS (62.7%) and 47 (37.3%) in the SS groups. The majority of the 126 exacerbations (101; 80.1%) were mild. The majority of the 102 exacerbations, where sputum examination was performed before any treatment (n=70), were noneosinophilic. In the SS patients, the time to the first exacerbation was longer (by 213 days) especially in those considered to need treatment with a long acting beta2-agonist (by 490 days), the relative risk ratio was lower (by 49%), and the number of exacerbations needing prednisone was reduced (5 versus 15). This benefit was seen mainly in patients needing treatment with inhaled steroid in a daily dose equivalent to fluticasone>250 microg, and was due to fewer eosinophilic exacerbations. The cumulative dose of corticosteroid during the trial was similar in both groups. Monitoring sputum cell counts was found to benefit patients with moderate-to-severe asthma by reducing the number of eosinophilic exacerbations and by reducing the severity of both eosinophilic and noneosinophilic exacerbations without increasing the total corticosteroid dose. It had no influence on the frequency of noneosinophilic exacerbations, which were the most common exacerbations.
Stabilizing effect of combined eicosapentaenoic acid and statin therapy on coronary thin-cap fibroatheroma.

The addition of highly purified eicosapentaenoic acid (EPA) to statin therapy prevents cardiovascular events. However, the impact of this treatment on vulnerable plaques remains unclear. The aim of this study was to assess the impact of adding EPA to a standard statin therapy on vulnerable plaques by serial optical coherence tomography (OCT).



Forty-nine non-culprit thin-cap fibroatheroma (TCFA) lesions in 30 patients with untreated dyslipidemia were included. Patients were randomly assigned to EPA (1800 mg/day) + statin (23 TCFA, 15 patients) or statin only (26 TCFA, 15 patients) treatment. The statin (rosuvastatin) dose was adjusted to achieve a target low-density lipoprotein (LDL) level of <70 mg/dL. Post-percutaneous intervention and 9-month follow-up OCT were performed to evaluate morphological changes of TCFAs. The EPA/arachidonic acid (EPA/AA) ratio and pentraxin-3 (PTX3) levels were also evaluated.



Despite similar follow-up LDL levels, the EPA + statin group had higher EPA/AA ratios and lower PTX3 levels than the statin group. OCT analysis showed that the EPA + statin group had a greater increase in fibrous-cap thickness, with a greater decrease in lipid arc and lipid length. Macrophage accumulation was less frequently detected in the EPA + statin group than in the statin group at follow-up. When the patients were categorized according to their follow-up PTX3 tertiles, fibrous-cap thickness showed significant increase, and the incidence of macrophages accumulation decreased with lower PTX3 levels.



The concomitant use of EPA and rosuvastatin may stabilize vulnerable plaques better than the statin alone, possibly by suppressing arterial inflammation.
Better clinical results after closed- compared to open-wedge high tibial osteotomy in patients with medial knee osteoarthritis and varus leg alignment

Studies comparing mid- or long-term outcomes of open- and closed-wedge high tibial osteotomy are limited. Here, the midterm survival rate and clinical and radiographic outcomes were compared for these two techniques. The study hypothesis, based on short-term follow-up, was that after midterm follow-up, the two techniques would not differ. A prospective follow-up study was conducted for a previously reported randomized controlled trial of an original 50 patients (25 open-wedge osteotomy and 25 closed-wedge osteotomy) with medial knee osteoarthritis and a varus leg alignment. We analyzed patients without knee arthroplasty (mean age 48.7 years, SD 8.0) for clinical and radiographic follow-up. Five patients in each group had undergone conversion to a total knee arthroplasty or unicompartmental knee arthroplasty, leaving 19 patients for analysis in each group. At 7.9 years of follow-up (range 7–9 years), survival did not differ significantly between groups (open-wedge group 81.3 % [95 % confidence interval (CI) 75.2–100], closed-wedge group 82.0 % [95 % CI 66.7–100]). At final follow-up, total Dutch Western Ontario and McMaster Universities Arthritis (WOMAC), Knee Society Score, and visual analog scale (VAS) pain did not differ between groups. However, the results were significantly better in the closed-wedge group for VAS satisfaction and WOMAC pain and stiffness compared to the open-wedge group. Radiographic evaluation did not differ between groups for any outcome at final follow-up. After a mean follow-up of 7.9 years, patients undergoing a closed-wedge osteotomy had favorable clinical results compared to those who underwent an open-wedge osteotomy. II.
Comparing exercise in Parkinson's disease--the Berlin LSVT®BIG study.

Physiotherapy is widely used in Parkinson's disease (PD), but there are few controlled studies comparing active interventions. Recently, a technique named "LSVT®BIG" has been introduced. LSVT®BIG is derived from the Lee Silverman Voice Treatment and focuses on intensive exercising of high-amplitude movements. In the present comparative study, 60 patients with mild to moderate PD were randomly assigned to receive either one-to-one training (BIG), group training of Nordic Walking (WALK), or domestic nonsupervised exercises (HOME). Patients in training (BIG) and WALK received 16 hours of supervised training within 4 (BIG) or 8 (WALK) weeks. The primary efficacy measure was difference in change in Unified Parkinson's Disease Rating Scale (UPDRS) motor score from baseline to follow-up at 16 weeks between groups. UPDRS scores were obtained by blinded video rating. ANCOVA showed significant group differences for UPDRS-motor score at final assessment (P < 0.001). Mean improvement of UPDRS in BIG was -5.05 (SD 3.91) whereas there was a mild deterioration of 0.58 (SD 3.17) in WALK and of 1.68 (SD 5.95) in HOME. LSVT®BIG was also superior to WALK and HOME in timed-up-and-go and timed 10 m walking. There were no significant group differences for quality of life (PDQ39). These results provide evidence that LSVT®BIG is an effective technique to improve motor performance in patients with PD.
Long-term azathioprine in rheumatoid arthritis: a double-blind study.

Several studies have demonstrated the beneficial effect of azathioprine in rheumatoid arthritis. But fears have been expressed about the possible mutagenic and teratogenic effects of prolonged use. If the drug could be withdrawn once remission is achieved, and this remission be then maintained with other agents, the possible complications of long-term therapy might be avoided. A double-blind controlled study was carried out over 8 months in 32 patients receiving long-term azathioprine therapy for rheumatoid arthritis. Substitution of placebo for active drug resulted in clinical deterioration.
Lack of survival improvement with novel anti-myeloma agents for patients with multiple myeloma and central nervous system involvement: the Greek Myeloma Study Group experience

Involvement of the central nervous system (CNS) is a rare complication of multiple myeloma (MM). Herein, we have described the incidence, characteristics, prognostic factors for post CNS-MM survival, and outcome of CNS-MM and explored the efficacy of novel agents (NA) (thalidomide, bortezomib, lenalidomide) in this setting. Between 2000 and 2013, 31 (0.9 %) out of 3408 newly diagnosed symptomatic MM patients, consecutively diagnosed and treated during the same period in 12 Greek centers, developed CNS-MM (M/F 15/16, median age 59 years, range 20–96 years; newly diagnosed/relapsed-refractory 2/29; median time to CNS-MM diagnosis 29 months). Clinical and laboratory characteristics were retrospectively recorded. Twenty-six percent of patients had circulating plasma cells (PCs) or plasma cell leukemia (PCL) at CNS-MM and 39 % had skull-derived plasmacytomas, suggesting hematological and contiguous spread. Treatment for CNS-MM was offered in 29/31 patients and 11/29 responded (NA 18/29, additional radiotherapy 9/28, intrathecal chemotherapy 13/29). The median post CNS-MM survival was 3 months (95 % CI 1.9–4.1) and did not differ between patients treated with NA and/or radiotherapy vs. others. In the multivariate analysis, prior treatment of MM with NA, extramedullary disease (EMD) during MM course (i.e., plasmacytomas, circulating PCs, or documented PCL) and abnormally high LDH at MM diagnosis were independent prognostic factors, whereas treatment of CNS-MM with NA did not predict for post CNS-MM survival. Despite the relatively limited number of patients due to the rarity of CNS-MM, our results suggest that NA do not seem to improve post CNS-MM survival. Patients with EMD display shortened post CNS-MM survival and should be followed thoroughly.
Clinical usefulness of the free web-based image analysis application ImmunoRatio for assessment of Ki-67 labelling index in breast cancer

Ki-67 is a prognostic marker in breast cancer; however, the use of the Ki-67 labelling index (LI) in clinical practice requires a consistent and easily accessible scoring method. The present study evaluated the use of the free internet-based image analysis program ImmunoRatio to score Ki-67 LI in breast cancer in comparison with manual counting.



Ki-67 immunohistochemical detection was performed in 577 breast cancer cases, and the Ki-67 LI was determined by ImmunoRatio and manual counting.



The Ki-67 LI determined by ImmunoRatio correlated well with that obtained by manual counting. The concordance rate between ImmunoRatio and manual counting was excellent (κ coefficient of 0.881) at a Ki-67 LI cut-off value of 20%. Cases with high Ki-67 LI by ImmunoRatio were associated with poor overall survival, in particular in the hormone receptor positive group.



The web-based automated image analysis program ImmunoRatio is an attractive alternative to manual counting to determine the Ki-67 LI in breast cancer.
Effect of the peritoneal dialysis prescription on pentosidine in children

Enhanced formation of advanced glycation end products (AGEs) by peritoneal dialysate containing high dextrose concentrations has been implicated as a source of peritoneal membrane toxicity and loss of viability in patients treated with peritoneal dialysis (PD). The goal of this project was to elucidate the relationship between the structurally defined AGE pentosidine accumulation on peritoneal and plasma proteins and peritoneal membrane function, and to identify clinical factors leading to alterations in these parameters. The study comprised 27 pediatric patients (14 continuous ambulatory PD, 13 chronic cycling PD) on PD for a mean duration of 37.0±22.8 months (range 1–120 months) and with a mean age of 13.3±4.4 years (range 2.4–20 years). The pentosidine contents of plasma and peritoneal proteins were significantly lower in patients with residual renal function than in patients who were anuric (plasma pentosidine 11.2±8.8 vs. 24.1±16.6, P=0.02, respectively, peritoneal pentosidine 14.9±11.9 vs. 31.1±3.7, P=0.01, respectively). There was no effect of treatment modality on plasma pentosidine (18.1±11.2, 18.8±19.3, CAPD vs. CCPD, P>0.05) or peritoneal pentosidine content (24.1±14.1, 24.9±19.6, CAPD vs. CCPD, P>0.05). There was no evidence that increased levels of pentosidine on peritoneal proteins reflect or affect peritoneal membrane function in these patients. Furthermore, there was no effect of peritonitis on the pentosidine content of peritoneal proteins or peritoneal function as measured by peritoneal equilibration test. In conclusion, PD represents a well-tolerated therapy in children with no evidence that current practice causes changes in peritoneal membrane function, or in the peritoneal clearance of plasma or peritoneal proteins rich in pentosidine.
The effect of antireflux treatment on patients with gastroesophageal reflux disease undergoing a mental arithmetic stressor.

Acute stress exacerbates heartburn in gastroesophageal reflux disease (GERD) patients by enhancing the perceptual responses to intraesophageal acid. The aim of the study was to determine if antireflux treatment can still alter stimulus response functions to acid in patients undergoing acute stress as compared with placebo.



Symptomatic GERD patients with erosive esophagitis (EE) or an abnormal pH test were included. Patients underwent stimulus response functions to intraesophageal acid perfusion using the mental arithmetic stressor test. Thereafter, patients were randomized (2 : 1 ratio) to either esomeprazole 40 mg once daily or placebo for 8 weeks. On the last day of treatment, subjects underwent stimulus response functions to intraesophageal acid perfusion using a similar stressor as baseline.



A total of 31 patients were randomized into the treatment arm (mean age 48.6 ± 2.8, M/F 21/10) and 16 into the placebo arm (mean age 52.3 ± 4.3, M/F 12/4). In the esomeprazole group, there was a significant increase in lag time to symptom perception (P = 0.02) and decreased in intensity rating (P = 0.01) as well as acid perfusion sensitivity score (P = 0.01). There was no significant difference in any of the stimulus response functions to acid in the placebo group between baseline and treatment. Interpersonal sensitivity was the only independent clinical predictor factor for response to antireflux treatment.


Long-term antireflux treatment with a proton pump inhibitor is effective in reducing esophageal perception responses to acid during acute stress.
Serum trace element levels in patients with bladder cancer.

Trace elements are essential components of biological structures, but they can be toxic at concentrations beyond those necessary for their biological functions. In the present study, groups of 35 patients with bladder cancer and 34 healthy volunteer controls were measured for trace elements using a furnace atomic absorption spectrophotometer. Serum levels of Cd, Ni and Co were increased (p<0.05) and Mn and Zn were decreased (p<0.05) in patients with bladder cancer. In the present study, a relationship was seen between the level of trace elements and the occurrence of bladder cancer, suggesting that an increase in the serum level of Cd, Ni, Co and a decrease in the levels of Zn and Mn might be important causes of bladder cancer occurrence; however, defining such a cause-and-effect relationship needs several prospective studies to be done, which seems necessary with regard to the high prevalence of this cancer.