nils-herrmann/clean_scirepeval huggingface dataset:
Evaluation of response to fractionated radioimmunotherapy with 90Y-epratuzumab in non-Hodgkin's lymphoma by 18F-fluorodeoxyglucose positron emission tomography.

The study aimed to evaluate FDG-PET imaging for early prediction of response to radioimmunotherapy in patients with non-Hodgkin's lymphoma.



Twenty-seven patients from a large ongoing, multicenter, phase I/II trial of fractionated radioimmunotherapy using anti-CD22 (90)Y-epratuzumab underwent FDG-PET imaging. They also underwent assessment by conventional diagnostic methods that included chemotherapy at baseline and six weeks post-radioimmunotherapy, and every three months until progression. Responses evaluated from conventional methods were classified using International Workshop Response Criteria as complete response, unconfirmed CR, partial response, stable disease, or progression of disease. FDG-PET images were evaluated visually and were classified as complete response, partial response or progression of disease. The gold standard was histology and follow-up.



A total of 81 paired imaging studies were obtained post-radioimmunotherapy (including 3 patients after retreatment) and evaluated as complete response (n=34), partial response (n=24) or progression of disease (n=23) by FDG-PET, and complete response (n=12), unconfirmed complete response (n=31), partial response (n=15), stable disease (n=8) or progression of disease (n=15) by conventional methods. Of the 31 responses evaluated as unconfirmed complete response by conventional methods, 20 (65%) were classified as negative for disease (complete response) by PET while the other 11 (35%) were positive for disease (7 partial response and 4 progression of disease). Among 22 assessable PET images acquired at six weeks post-radioimmunotherapy, the mean time-to-progression was 15.6 months when PET was negative for disease (complete response), compared with 5.4 months when PET was positive (partial response or progression of disease) (p=0.008). Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of PET six weeks after radioimmunotherapy were 86%, 63%, 80%, 71% and 77% respectively, compared with 36%, 87%, 83%, 44% and 55% respectively using conventional methods.



A positive assessment of disease by PET acquired six weeks after radioimmunotherapy corresponded with a shorter time to progression.
Using a state cancer registry to recruit young breast cancer survivors and high-risk relatives: protocol of a randomized trial testing the efficacy of a targeted versus a tailored intervention to increase breast cancer screening

The Michigan Prevention Research Center, the University of Michigan Schools of Nursing, Public Health, and Medicine, and the Michigan Department of Community Health propose a multidisciplinary academic-clinical practice three-year project to increase breast cancer screening among young breast cancer survivors and their cancer-free female relatives at greatest risk for breast cancer. The study has three specific aims: 1) Identify and survey 3,000 young breast cancer survivors (diagnosed at 20–45 years old) regarding their breast cancer screening utilization. 2) Identify and survey survivors’ high-risk relatives regarding their breast cancer screening utilization. 3) Test two versions (Targeted vs. Enhanced Tailored) of an intervention to increase breast cancer screening among survivors and relatives. Following approval by human subjects review boards, 3,000 young breast cancer survivors will be identified through the Michigan Cancer Registry and mailed an invitation letter and a baseline survey. The baseline survey will obtain information on the survivors’: a) current breast cancer screening status and use of genetic counseling; b) perceived barriers and facilitators to screening; c) family health history. Based on the family history information provided by survivors, we will identify up to two high-risk relatives per survivor. Young breast cancer survivors will be mailed consent forms and baseline surveys to distribute to their selected high-risk relatives. Relatives’ baseline survey will obtain information on their: a) current breast cancer screening status and use of genetic counseling; and b) perceived barriers and facilitators to screening. Young breast cancer survivors and high-risk relatives will be randomized as a family unit to receive two versions of an intervention aiming to increase breast cancer screening and use of cancer genetic services. A follow-up survey will be mailed 9 months after the intervention to survivors and high-risk relatives to evaluate the efficacy of each intervention version on: a) use of breast cancer screening and genetic counseling; b) perceived barriers and facilitators to screening; c) self-efficacy in utilizing cancer genetic and screening services; d) family support related to screening; e) knowledge of breast cancer genetics; and f) satisfaction with the intervention. The study will enhance efforts of the state of Michigan surrounding cancer prevention, control, and public health genomics.
The effects of sulfasalazine treatment on enthesal abnormalities of inflammatory rheumatic diseases

The aim of this study was to evaluate the effects of a 1-year course of sulfasalazine monotherapy on enthesal abnormalities of inflammatory rheumatic diseases (IRDs) using ultrasonography. Thirty-six patients with IRD including 20 patients with rheumatoid arthritis (RA) and 16 patients with ankylosing spondylitis (AS) (22 women, 14 men, mean ages 43.3 ± 8.8 years), and 18 healthy controls (10 women, 8 men, mean ages 42.5 ± 9.9 years) matched by age and body mass index were enrolled in this study. For the evaluation of enthesal structures, all patients and controls underwent ultrasonographic (USG) examinations of five enthesal sites of both lower limbs using high-resolution and Doppler USG. An ultrasonographic score of lower limb enthesitis was calculated using Glasgow ultrasound enthesitis scoring system (GUESS). Clinical and laboratory activities of IRD patients were also evaluated. Patient group was made to undergo 2 g/day sulfasalazine monotherapy for 1 year. All evaluations were made at the beginning of the treatment and repeated after 1 year follow-up. Results showed that the frequency of enthesal abnormalities of the IRD group was significantly higher than controls. On USG examination, 301/1,296 (23.2%) enthesal structures were abnormal in IRD patients, and 19/648 (2.93%) structures were abnormal in controls. Mean GUESS score of the IRD group (6.40 ± 2.41) was also significantly higher than controls (1.79 ± 1.60) (p < 0.001). Although there was a significant improvement in clinical and laboratory activity parameters of the IRD patients, significant decrease was not observed in enthesal abnormalities (295/1,296 enthesal structures—22.7%) and mean GUESS score (6.20 ± 2.38) after 1 year sulfasalazine trial. Additionally, there was no significant improvement in enthesal abnormalities and mean GUESS scores of AS and RA subgroups separately. Sulfasalazine treatment was not found effective on enthesal abnormalities of IRD patients. Further studies with larger groups including other IRDs are required to validate our results.
Alexithymia, depression, inflammation, and pain in patients with rheumatoid arthritis.

We previously reported that depression and inflammation have independent effects on pain severity in patients with rheumatoid arthritis (RA). Alexithymia is a personality trait characterized by deficits in cognitive processing and regulation of emotions. A broad association between alexithymia and various health problems has been suggested, including depression, inflammation, and pain. The objective of this study was to examine the independent influence of alexithymia on pain perception and its relationship to depression and inflammation.



We evaluated 213 RA outpatients who completed self-administered questionnaires, including the Beck Depression Inventory-II (BDI-II) to measure depression severity, the 20-item Toronto Alexithymia Scale (TAS-20) to measure degree of alexithymia, and a visual analog scale to quantify perceived pain. Serum C-reactive protein (CRP) levels were measured to quantify inflammation severity.



An initial significant positive association between the TAS-20 score and pain severity (P = 0.01) lost significance after controlling for BDI-II score and CRP level using regression analysis. An interaction was observed among alexithymia, depression, and inflammation with regard to perceived pain. Among those without alexithymia, pain severity increased linearly with the CRP tertile levels regardless of the presence of depression (P < 0.001 for trend). No linear association between pain severity and CRP level was observed among those with alexithymia. Moreover, depressed patients with alexithymia (BDI-II score ≥14 and TAS-20 score ≥61) reported severe pain even at low CRP levels.



Alexithymia might have a substantial role in pain perception as well as depression in patients with RA. A biopsychosocial approach is essential to achieve better pain control.
Effects of renal sympathetic denervation on exercise blood pressure, heart rate, and capacity in patients with resistant hypertension.

Renal denervation reduces office blood pressure in patients with resistant hypertension. This study investigated the effects of renal denervation on blood pressure, heart rate, and chronotropic index at rest, during exercise, and at recovery in 60 patients (renal denervation group=50, control group=10) with resistant hypertension using a standardized bicycle exercise test protocol performed 6 and 12 months after renal denervation. After renal denervation, exercise blood pressure at rest was reduced from 158±3/90±2 to 141±3/84±4 mm Hg (P<0.001 for systolic blood pressure/P=0.007 for diastolic blood pressure) after 6 months and 139±3/83±4 mm Hg (P<0.001/P=0.022) after 12 months. Exercise blood pressure tended to be lower at all stages of exercise at 6- and 12-month follow-up in patients undergoing renal denervation, although reaching statistical significance only at mild-to-moderate exercise levels (75-100 W). At recovery after 1 minute, blood pressure decreased from 201±4/95±2 to 177±4/88±2 (P<0.001/P=0.066) and 188±6/86±2 mm Hg (P=0.059/P=0.01) after 6 and 12 months, respectively. Heart rate was reduced after renal denervation from 71±3 bpm at rest, 128±5 bpm at maximum workload, and 96±5 bpm at recovery after 1 minute to 66±2 (P<0.001), 115±5 (P=0.107), and 89±3 bpm (P=0.008) after 6 months and to 69±3 (P=0.092), 122±7 (P=0.01), and 93±4 bpm (P=0.032) after 12 months. Mean exercise time increased from 6.59±0.33 to 8.4±0.32 (P<0.001) and 9.0±0.41 minutes (P=0.008), and mean workload increased from 93±2 to 100±2 (P<0.001) and 101±3 W (P=0.007) at 6- and 12-month follow-up, respectively. No changes were observed in the control group. In conclusion, renal denervation reduced blood pressure and heart rate during exercise, improved mean workload, and increased exercise time without impairing chronotropic competence.
Multimodal biochemical modulation of 5-fluorouracil by leucovorin, methotrexate, and interferon alpha in patients with advanced colorectal cancer

A total of 26 patients with advanced colorectal cancer received 60 mg/m2 methotrexate i. v. on days 1 – 4; 400 mg/m2 5-fluorouracil i. v. on days 2, 3, 5, and 6; and 100 mg/m2 6S-leucovorin i. v. on days 2, 3, 5, and 6. Interferon-α2b at a dose of 3 million U was given i. m. daily for the 6 days of chemotherapy. Courses were repeated every 3 weeks. There were four partial responses for a response rate of 15% (95% confidence interval 2 – 28%). In all, 14 patients expressed grade 3 toxicity; 9 patients had diarrhea, 3 had stomatitis, and 2 developed leukopenia. In conclusion, multimodal biochemical modulation of 5-fluorouracil, at least on this schedule, does not seem to be effective, as it results in severe toxicity.
Endogenous interleukin 6 production in multiple myeloma patients treated with chimeric monoclonal anti-IL6 antibodies indicates the existence of a positive feed-back loop.

In vitro as well as in vivo observations have shown that IL6 plays a key role in the pathogenesis of multiple myeloma. Therefore we started a phase I/II dose escalating study with chimeric monoclonal anti-IL6 antibodies (cMab) in multiple myeloma (MM) patients resistant to second-line chemotherapy. Here we describe the pharmacological data as well as a new method for calculating the endogenous IL6 production. The cMab (CLB IL6/8; Kd: 6.25 x 10(-12) M) was given in two cycles of 14 daily infusions, starting on day 1 and day 28.  5 mg in patients 1-3, 10 mg in patients 4-6, and 20 mg in patients 7-9 (total dose 140, 280, and 560 mg of anti-IL6, respectively). Using the pharmacokinetic data of free IL6 and the binding characteristics of the cMab, the endogenous IL6 production could be calculated from day to day using a one-compartment open model. The median half-life time of this antibody was 17.6 d. No human antichimeric antibodies were induced. Pre-treatment median endogenous IL6 production in the MM patients was 60 micrograms/d (range 13.8-230; normal controls < 7 micrograms/d). During treatment with anti-IL6 cMabs, the endogenous IL6 production immediately decreased in all patients to below 3 micrograms/d and never reached the pre-treatment value during the treatment period, except in two patients who developed an active infection, resulting in an IL6 production of 128 and 1,208 micrograms/d, respectively. We concluded that in MM patients endogenous IL6 production is 2-30 times higher than in healthy individuals. The anti-IL6 cMab strongly suppress this endogenous IL6 production, probably by blocking a positive feed-back loop, but this cMab does not prevent infection-induced IL6 production. The chimeric anti-IL6 Mabs have a long half-life time, a low immunogenicity, and are able to block IL6-dependent processes in vivo.
Prevention of tolerance to hemodynamic effects of nitrates with concomitant use of hydralazine in patients with chronic heart failure.

This study was designed to determine the effect of oral hydralazine on the development of nitrate tolerance in patients with chronic congestive heart failure.



Early development of nitrate tolerance with either continuous administration of intravenous or topical nitrate preparations or frequent dosing of oral nitrates leads to significant attenuation of nitrate-mediated hemodynamic and anti-ischemic effects. In recent animal experiments, prevention of nitroglycerin-induced hemodynamic tolerance with a concomitant use of hydralazine was demonstrated. This finding may have important clinical relevance.



Twenty-eight patients with chronic heart failure due to left ventricular systolic dysfunction were randomized to receive either a continuous infusion (24 h) of nitroglycerin alone (group I, 14 patients) or concomitantly with oral hydralazine (75 mg four times a day [group II, 14 patients]). The effect of nitroglycerin in each group was evaluated by analysis of variance for repeated measures. The power of the analysis to detect a 5.4-mm Hg (20%) change in mean pulmonary artery wedge pressure was 90%.



Baseline hemodynamic variables as well as the initial hemodynamic response to nitroglycerin were comparable in both groups. Compared with the initial response to nitroglycerin, a significant attenuation of effect was found in group I at 24 h in mean (+/- SE) pulmonary artery pressure (27 +/- 4% vs. 10 +/- 3%, p < 0.05) and mean pulmonary artery wedge pressure (40 +/- 4% vs. 16 +/- 4%, p < 0.05). In group II, conversely, oral hydralazine prevented nitroglycerin-induced hemodynamic tolerance and resulted in a persistent effect on mean pulmonary artery and wedge pressures throughout the study period (31 +/- 3% vs. 27 +/- 4%, p = 0.13 and 37 +/- 4% vs. 34 +/- 6%, p = 0.40, respectively). In addition, the initial effect on blood pressure was attenuated at 24 h in group I (5 +/- 2% vs. 12 +/- 3%, p < 0.05) but not in group II (15 +/- 3% vs. 17 +/- 2%, p = 0.46).



In patients with chronic heart failure due to left ventricular systolic dysfunction, the concomitant use of oral hydralazine prevents early development of nitrate tolerance and results in a persistent nitrate-mediated hemodynamic effect on systemic and pulmonary artery and left ventricular filling pressures. These data may support the concurrent use of hydralazine in patients with heart failure treated with organic nitrates.
Double-blind crossover comparison of piroxicam and indomethacin in rheumatoid arthritis

This 10-week, double-blind, crossover study compared piroxicam (20 mg administered once daily) and indomethacin (25 mg administered three times daily) in patients with rheumatoid arthritis. In the 30 patients evaluated, both drugs produced statistically significant improvement after 4 weeks compared to placebo in all parameters measured with the exception of joint swelling and 10 m walking time. Piroxicam provided greater improvement with respect to the severity of pain, joint tenderness and restoration of motion, and was significantly more effective than indomethacin in reducing the consumption of paracetamol and in improving morning stiffness. Both drugs were equally effective in improving the remaining parameters measured. Roughly, two-thirds of the patients considered piroxicam to be the more effective agent. With both drugs side effects were mild and infrequent.
Genetic risk factors in Parkinson’s disease: single gene effects and interactions of genotypes

Parkinson’s disease (PD) is a common neurodegenerative disorder for which genetic causes and susceptibility factors have been identified using linkage and association studies . Many candidate genes have been investigated as risk factors for PD (www.pdgene.org) and several genome-wide association studies (GWAS) as well as three meta-analyses have been reported [4, 9, 10]. All GWAS indicate a strong association to several polymorphisms within the alpha-synuclein (SNCA) gene, encoding a protein highly concentrated at presynaptic nerve terminals . Most studies also confirm an association with the H1/H2 haplotype of the microtubule-associated protein tau (MAPT) gene that is enriched in axons . In addition, the S18Y (rs5030732) polymorphism in the ubiquitin carboxyl-terminal hydrolase L1 (UCHL1), a neuron-specific enzyme that is involved in protein degradation, has been shown to modify enzymatic activity and to protect against PD [7]. N-acetyl transferase 2 (NAT2) is an enzyme responsible for the biotransformation of neurotoxins. An inherited defect, which results in a slower rate of metabolism, can lead to greater vulnerability to neurotoxins and to a higher susceptibility of PD . However, to date, all known risk factors explain only part of the heritability of PD and thus suggest additional genetic contributions. This might include interactions of genetic risk factors. After obtaining informed consent, we included 400 Caucasian PD patients enrolled in a clinical study in the US [12] and 353 controls from the US from the NINDS Human Genetics DNA Repository at the Coriell Institute for Medical Research. For diagnosis, the presence of bradykinesia was required in combination with at least one other cardinal symptom, i.e., rigidity, resting tremor, or postural instability . All patients were diagnosed within 5 years of enrollment. The study was approved by the local ethics committees and performed in accordance with the Declaration of Helsinki. We genotyped seven polymorphisms in six genes (Table 1, part A) previously reported as common genetic risk factors for PD . Genotyping methods included polyacrylamide gel electrophoresis, melting curve analysis, PCR fragment length determination, and direct sequencing. NAT2 metabolizer phenotype was inferred using a validated discriminator . PD risk attributable to each gene and their two-way interactions were estimated by logistic regression controlling for age and gender. Two-tailed p values for the seven single gene effects and for the 21 possible two-gene interactions were adjusted for multiple comparisons using a step-down Bonferroni correction. Consistent with the current literature , a significant association of PD risk was detected for both SNCA polymorphisms (Table 1, part A). No single gene association was found for any of the other genes including MAPT. A. Göbel S. Winkler C. Klein K. Lohmann (&) Section of Clinical and Molecular Neurogenetics, Department of Neurology, University of Lübeck, Ratzeburger Allee 160, 23538 Lubeck, Germany e-mail: katja.lohmann@neuro.uni-luebeck.de
Impact of saphenous vein graft radiographic markers on clinical events and angiographic parameters.

Use of saphenous vein graft (SVG) radiographic markers has been associated with shorter cardiac catheterization procedure times and reduced contrast agent volume for postoperative coronary artery bypass graft (CABG) catheterizations. Use of such markers is varied and often operator-dependent, as the effect of SVG markers has not been fully evaluated. The goal of the present analysis was to evaluate the association of SVG markers with clinical outcomes and graft patency.



Data were drawn from the Project of Ex-vivo Vein Graft Engineering via Transfection (PREVENT) IV trial of patients undergoing CABG at 107 hospitals across the United States. Repeat angiography was performed within 12 to 18 months after CABG. The SVG markers were used at the discretion of the surgeon and were identified on the follow-up angiogram as any device used to mark the ostium, regardless of shape.



The SVG markers were present in 51.2% of evaluable patients (910 of 1,778) and 52.3% of SVGs (2,228 of 4,240). Among patients with totally occluded SVGs (n = 911), visual identification of the SVG was obtained more frequently in those with an SVG marker (90.7% vs 72.1%, p < 0.001). The SVG stenosis 70% or greater at follow-up did not differ by use of markers (25.8% with marker vs 24.4% without marker, p = not significant). These findings were also consistent in ostial lesions (n = 942). Long-term death or myocardial infarction (MI) was similar by use of marker. The perioperative CABG MI was higher in patients with SVG markers (10.1% vs 5.5%, odds ratio adjusted 1.86, p = 0.021).



Saphenous vein graft radiographic markers were associated with higher rates of direct visualization of totally occluded SVGs without an adverse effect on graft patency or long-term clinical outcomes, but the association of SVG markers with increased perioperative CABG MI warrants further examination.