nils-herrmann/clean_scirepeval huggingface dataset:
Response assessment in patients with multiple myeloma during antiangiogenic therapy using arterial spin labeling and diffusion-weighted imaging: a feasibility study.

To determine whether response to anti-angiogenic therapy in patients with multiple myeloma can be assessed by noncontrast perfusion magnetic resonance imaging (MRI) (ie, arterial-spin-labeling [ASL]), and diffusion-weighted [DWI] MRI.



The study protocol was approved by the local institutional ethic board. Ten consecutive patients (eight men, two women; mean age 60.5 ± 8.5 years) with Stage III multiple myeloma were prospectively included. MRI was performed at baseline, as well as 3 and 8 weeks after onset of antiangiogenic therapy. Functional MRI data were compared with clinical outcome and conventional lesion size and signal-intensity measurements. Differences between baseline and follow-up values for ASL-MRI and DWI-MRI were assessed using a paired Student t-test.



Nine patients responded well to therapy, whereas one patient was classified a nonresponder. Temporary changes in signal intensity between baseline and follow-up examinations were inconsistent on T1-weighted (w) and T2w images. Likewise, determination of lesion size at follow-up proved unreliable. ASL showed a marked decrease in perfusion from baseline (251 ± 159 mL/(min*100g)) to follow-up at 3 weeks (115 ± 85 mL/(min*100g), P = .01) and 8 weeks (101 ± 90 mL/(min*100g, P = .01), respectively. Relative to the baseline examination, mean diffusion increased from 0.68 ± 0.19 × 10(-3) s/mm(2) at baseline to 0.94 ± 0.24 × 10(-3) s/mm(2) after 3 weeks (P = .04), and 0.96 ± 0.40 × 10(-3) s/mm(2) after 8 weeks (P = .049). Both methods were able to correctly classify 9/10 patients as responder or nonresponder.



ASL perfusion as well as DWI-MRI provide accurate, clinically relevant information regarding tumor viability and can predict response already early after therapy onset, as opposed to classical lesion size and MRI signal-intensity measurements.
Additive effects of raloxifene and alendronate on bone density and biochemical markers of bone remodeling in postmenopausal women with osteoporosis.

Both raloxifene (RLX) and alendronate (ALN) can treat and prevent new vertebral fractures, increase bone mineral density (BMD), and decrease biochemical markers of bone turnover in postmenopausal women with osteoporosis. This phase 3, randomized, double-blind 1-yr study assessed the effects of combined RLX and ALN in 331 postmenopausal women with osteoporosis (femoral neck BMD T-score, less than -2). Women (aged < or = 75 yr; > or = 2 yr since their last menstrual period) received placebo, RLX 60 mg/d, ALN 10 mg/d, or RLX 60 mg/d and ALN 10 mg/d combined. At baseline, 6 and 12 months, BMD was measured by dual x-ray absorptiometry. The bone turnover markers serum osteocalcin, bone-specific alkaline phosphatase, and urinary N- and C-telopeptide corrected for creatinine were measured. The effects of RLX and ALN were considered to be independent and additive if the interaction effect was not statistically significant (P > 0.10) in a two-way ANOVA model. All changes in BMD and bone markers at 12 months were different between placebo and each of the active treatment groups, and between the RLX and RLX+ALN groups (P < 0.05). On average, lumbar spine BMD increased by 2.1, 4.3, and 5.3% from baseline with RLX, ALN, and RLX+ALN, respectively. The increase in femoral neck BMD in the RLX+ALN group (3.7%) was greater than the 2.7 and 1.7% increases in the ALN (P = 0.02) and RLX (P < 0.001) groups, respectively. The changes from baseline to 12 months in bone markers ranged from 7.1 to -16.0% with placebo, -23.8 to -46.5% with RLX, -42.3 to -74.2% with ALN, and -54.1 to -81.0% in the RLX+ALN group. RLX and ALN increased lumbar spine and femoral neck BMD, and decreased osteocalcin and C-telopeptide corrected for creatinine in an additive and independent manner, because the interaction effects were not significant. Although the ALN group had changes in BMD and bone markers that were approximately twice the magnitude as in the RLX group, it is not known how well these changes correlate to the clinical outcome of fracture. RLX+ALN reduced bone turnover more than either drug alone, resulting in greater BMD increment, but whether this difference reflects better fracture risk reduction was not assessed in this study.
Five questions predicted long-term, severe, back-related functional limitations: evidence from three large prospective studies.

The objectives of the study were as follows: (1) to investigate whether the predictive validity of a previously developed back pain prediction rule could be improved; (2) to determine if the rule can be shortened without loss of predictive validity; (3) to compare the rule with the physician's judgment; (4) to assess, in a different population, its 2-year predictive validity; and (5) to evaluate the clinical applicability of the rule in a first-line care setting.



One thousand two hundred and sixty-two participants were enrolled in the study (participation: 91%) before a medical consultation for nonspecific back pain in a large emergency room and were followed up for 2 years (follow-up: 92.5%). The effects of adding new items and deleting any one of the original items were evaluated. The predictions by the rule and the physicians were compared with the 2-year actual functional limitations (measured with the Roland-Morris Disability Questionnaire).



Although the final prediction rule included only five items (feeling everything is an effort, trouble getting breath, hot/cold spells, numbness/tingling in parts of body, and pain in heart/chest), its predictive validity was greater than that of the original 17-item version and was superior to the physician's prediction. The rule was easily applied.



A five-item clinical prediction rule of long-term back-related functional limitations could help first-line care physicians to concentrate the clinical attention on patients at higher risk.
Impact of acute caffeine ingestion on endothelial function in subjects with and without coronary artery disease.

Although coffee is a widely used, pharmacologically active beverage, its impact on the cardiovascular system is controversial. To explore the effect of acute caffeine ingestion on brachial artery flow-mediated dilation (FMD) in subjects without coronary artery disease (CAD; controls) and patients with CAD, we prospectively assessed brachial artery FMD in 40 controls and 40 age- and gender-matched patients with documented stable CAD on 2 separate mornings 1 week to 2 weeks apart. After overnight fasting, discontinuation of all medications for ≥12 hours, and absence of caffeine for >48 hours, participants received capsules with caffeine 200 mg or placebo. One hour after drug ingestion, participants underwent brachial artery FMD and nitroglycerin-mediated dilation (NTG) using high-resolution ultrasound. As expected, patients with CAD were more often diabetic, hypertensive, obese, dyslipidemic, and smoked more than controls (p <0.01 for all comparisons). Aspirin, Clopidogrel, angiotensin-converting enzyme inhibitors, β blockers, and statins were significantly more common in patients with CAD than in controls (p <0.01 for all comparisons). At baseline, FMD, but not NTG, was significantly lower in patients with CAD compared to controls. Acute caffeine ingestion significantly increased FMD (patients with CAD 5.6 ± 5.0% vs 14.6 ± 5.0%, controls 8.4 ± 2.9% vs 18.6 ± 6.8%, p <0.001 for all comparisons) but not NTG (patients with CAD 13.0 ± 5.2% vs 13.8 ± 6.1%, controls 12.9 ± 3.9% vs 13.9 ± 5.8%, p = NS for all comparisons) and significantly decreased high-sensitivity C-reactive protein (patients with CAD 2.6 ± 1.4 vs 1.4 ± 1.2 mg/L, controls 3.4 ± 3.0 vs 1.2 ± 1.0 mg/L, p <0.001 for all comparisons) in the 2 groups compared to placebo. In conclusion, acute caffeine ingestion significantly improved endothelial function assessed by brachial artery FMD in subjects with and without CAD and was associated with lower plasma markers of inflammation.
Chlamydia pneumoniae and progression of subclinical atherosclerosis.

Cross-sectional investigation between presence of antibodies and coronary artery calcification (CAC) in past studies has shown no relationship, but progression over time has not been investigated. The objective of this study was to determine the relationship between presence of Chlamydia pneumoniae antibodies and progression of CAC and ankle-brachial index (ABI).



The Multiethnic Study of Atherosclerosis (MESA) is a prospective population-based cohort of racially and ethnically diverse male and female participants recruited from six communities in the USA, age 45-84 years, free of clinical cardiovascular disease at baseline.



The main outcomes were progression of mean CAC and ABI between exams 1 (2000-02) and 3 (2004-05) (median follow-up of 3.13 years) by C. pneumoniae antibody. Multivariate models adjusting for demographics, obesity, smoking, alcohol use, and physical activity were computed.



Of 2223 subjects analysed, 76% were positive for C. pneumoniae antibodies. Progression of CAC was significantly higher in the antibody-positive group (93.8 vs. 78.2 agatston units, p = 0.02) and in antibody-positive subjects with CAC ≥10 at baseline (216.5 vs. 178.6, p = 0.02) than antibody-negative group. Smoking and body mass index ≥30 kg/m(2) both had interactions with presence of C. pneumoniae yielding significantly greater CAC progression. Progression of ABI did not significantly differ by C. pneumoniae antibody status in models adjusted for covariates.



C. pneumoniae antibodies are related to progression of CAC, particularly in individuals with CAC present at baseline. This provides evidence that certain groups are at higher risk of atherosclerotic progression and may be useful for risk stratification and treatment.
Long-term outcome with cardiac resynchronization therapy in mild heart failure patients with left bundle branch block from US and Europe MADIT-CRT

Early intervention with cardiac resynchronization therapy with defibrillator (CRT-D) in mild heart failure (HF) patients with a left bundle branch block (LBBB) ECG pattern was associated with a significant reduction in mortality in the long-term MADIT-CRT trial. Whether patients in MADIT-CRT enrolled from centers in the USA and in Europe have different long-term clinical response to CRT-D remains unknown. We compared the baseline clinical characteristics and clinical and echocardiographic long-term clinical response to CRT-D between MADIT-CRT patients with LBBB who were enrolled in USA (n = 871) and European centers (n = 392). Although European patients had more advanced heart disease than US patients, CRT-D was associated with similar 60 % (p < 0.001) reductions in the risk of HF in US and European patients when compared to ICD-only therapy after adjustment for relevant baseline clinical covariates. US patients had significant long-term mortality reduction (38 %, p = 0.02) while among European patients the survival benefit associated with CRT-D was not statistically significant (HR 0.73, p = 0.18); subgroup analyses revealed a significantly greater CRT-D benefit among women who were enrolled in the USA, whereas no significant gender difference in the clinical benefit of CRT-D was observed in the European cohort. Reverse remodeling at 1 year was associated with significantly better clinical outcomes in both groups. Despite differences in baseline disease severity, European and US patients with LBBB experienced a similar clinical and echocardiographic response to cardiac resynchronization therapy during long-term follow-up.
Epitope presentation is an important determinant of the utility of antigens identified from protein arrays in the development of autoantibody diagnostic assays.

Autoantibodies represent an attractive biomarker for diagnostic assays principally due to the stability of immunoglobulin in patient serum facilitating measurement with conventional assays. Immune responses to tumorigenesis may facilitate detection of ovarian cancer in the early stages of the disease with identification of a panel of tumour specific autoantibodies. Despite the reporting of many tumour associated autoantibodies using arrays of tumour antigens, this has not led to the advance in diagnostic capability as rapidly as was initially expected. Here we examine the potential diagnostic utility of candidate autoantibody biomarkers identified via screening of serum samples on a high content human protein array from a unique cohort of early stage and late stage ovarian cancer patients. We analyse the performance of autoantibodies to the tumour suppressor protein p53 and the novel autoantigens alpha adducin and endosulfine alpha identified in our array screen. Each antigen has different performance characteristics using conventional ELISA format and Western blot immunoassay. The high attrition rate of promising autoantigens identified by array screening can in part be explained by the presentation of the epitope of the antigen in the subsequent method of validation and this study provides directions on maximising the potential of candidate biomarkers. This article is part of a Special Issue entitled: Translational Proteomics.
Allogenic platelet gel in the treatment of pressure sores: a pilot study.

Although platelet gel is considered one of the most popular tools in the treatment of chronic ulcers, current consensus on its use is not unanimous. A prospective randomised trial was carried out at the Plastic Surgery Unit of the 'Salvatore Maugeri' Foundation Hospital of Pavia (Italy). The study involved 13 patients affected by spinal cord injury with 16 pressure sores over a period of 20 months. The ulcer was considered the experimental unit of the study irrespective of the number of ulcers per patient. Each consecutive ulcer was randomised to be treated either with allogenic platelet gel or with current best practice approach to chronic wounds dressing protocol. At the end of the treatment 15 ulcers out of 16 improved clinically. No statistically significant difference was demonstrated in volume reduction between the two groups, although a statistically significant difference could be demonstrated in the onset time of granulation tissue proliferation as in the wounds treated with platelet gel the healing process was triggered earlier. Our study suggests that platelet gel is mostly effective within the first 2 weeks of treatment while a prolonged treatment does not provide any significant advantage versus the current best practice approach to chronic wounds protocols.
WT1 peptide vaccinations induce CD4 and CD8 T cell immune responses in patients with mesothelioma and non-small cell lung cancer

The transcription factor, WT1, is highly overexpressed in malignant pleural mesothelioma (MPM) and immunohistochemical stains for WT1 are used routinely to aid in its diagnosis. Using computer prediction analysis we designed analog peptides derived from WT1 sequences by substituting amino acids at key HLA-A0201 binding positions. We tested the safety and immunogenicity of a WT1 vaccine comprised of four class I and class II peptides in patients with thoracic neoplasms expressing WT1. Therapy consisted of six subcutaneous vaccinations administered with Montanide adjuvant on weeks 0, 4, 6, 8, 10, and 12, with 6 additional monthly injections for responding patients. Injection sites were pre-stimulated with GM-CSF (70 mcg). Immune responses were evaluated by DTH, CD4 T-cell proliferation, CD8 T-cell interferon gamma release, intracellular cytokine staining, WT1 peptide MHC-tetramer staining, and cytotoxicity against WT1 positive tumor cells. Nine patients with MPM and 3 with NSCLC were vaccinated, with 8 patients receiving at least 6 vaccinations; in total, 10 patients were evaluable for immune response. Six out of nine patients tested demonstrated CD4 T-cell proliferation to WT1 specific peptides, and five of the six HLA-A0201 patients tested mounted a CD8 T-cell response. Stimulated T cells were capable of cytotoxicity against WT-1 positive cells. Vaccination also induced polyfunctional CD8 T cell responses. This multivalent WT1 peptide analog vaccine induces immune responses in a high proportion of patients with thoracic malignancies with minimal toxicity. A randomized trial testing this vaccine as adjuvant therapy in MPM is planned.
Rehabilitation of patients with spinal cord lesions in the Netherlands: an epidemiological study

Very little is known about the occurrence of spinal cord lesions and results of the rehabilitation of patients with such lesions in the Netherlands. This study was conducted to describe the process of rehabilitation in the Dutch situation, to assess the incidence of spinal cord lesions in a regional rehabilitation centre and to characterise differences between traumatic and non-traumatic spinal cord lesions regarding age, level and extent of lesion. In this study 293 patients were included who were admitted to the rehabilitation centre between 1982 and 1993. Sixty-six per cent of this group came from the university hospital. The mean length of stay in the rehabilitation centre was 154 days. After completing the rehabilitation programme 94% of patients went home. Sixteen new SCI patients per million per year were admitted to the rehabilitation centre. Of our group 52% had a non-traumatic lesion, which concerned older patients with more incomplete lesions. In our opinion close collaboration between the university hospital and the rehabilitation centre is needed for optimal rehabilitation. Attention to independent living programmes and appropriate housing facilities can shorten the length of stay and increase the number of discharges of patients to their own environment. For patients with non-traumatic spinal cord lesions special programmes should be made available.
The minimal clinically important difference in the Gastrointestinal Quality-of-Life Index after cholecystectomy

The minimal clinically important difference (MCID) for the Gastrointestinal Quality of Life Index (GIQLI) is unknown, which limits its application and interpretation. This study aimed to estimate MCIDs for the GIQLI scores of patients after they had undergone cholecystectomy. This study had 267 participants. All the participants completed the GIQLI and four anchor items, namely, “How would you describe your overall symptoms, emotions, physical functions, and social functions since your last visit?” The response options were “much worse,” “somewhat worse,” “same,” “somewhat better” and “much better.” The MCID was defined according to those who responded with “somewhat better.” The mean age of the participants was 57.81 ± 14.93 years, and 37.08% of the patients were women. The MCID group included 67, 78, 44, and 22 patients with MCIDs of 6.42, 6.86, 7.64 and 6.46 points respectively for scores on the symptoms, emotions, physical functions, and social functions subscales, respectively. The effect sizes of four anchors in the “somewhat better” group (0.38–0.49) exceeded those of the same group (0.25–0.38). This study showed that after patients had undergone cholecystectomy, the clinically significant mean changes in their scores on the GIQLI subscales for symptoms, emotions, physical functions, and social function were respectively 6.42, 6.86, 7.64, and 6.46 points. After patients have undergone cholecystectomy, the MCIDs for the GIQLI subscales can play an important role in interpretation of the scores, application of them in clinical practice, and verification of treatment effects.
Use of Colon Cancer Testing in Rural Colorado Primary Care Practices

People living in rural areas may be less likely to be up to date (UTD) with screening guidelines for colorectal cancer (CRC). To determine (1) rates of being UTD with screening or ever having had a test for CRC and (2) correlates for testing among patients living in a rural area who visit a provider. Cross-sectional survey. Five hundred seventy patients aged 50 years and older who visited their health-care provider in High Plains Research Network (HPRN) practices. (1) Ever having had a CRC screening test, (2) being UTD with CRC screening, and (3) intention to get tested. The survey completion rate was 65%; 71% of patients had ever had any CRC screening test, while 52% of patients were UTD. Correlates of intending to get tested included having a family history of CRC, having a doctor recommend a test, knowing somebody who got tested, and believing that testing for CRC gives one a feeling of being in control of their health. Of those who had never had a CRC screening test, 12% planned on getting tested in the future, while 55% of those who were already up to date intended to be tested again (p < 0.001). Prevalence of being UTD with CRC testing in the HPRN was on par with statewide CRC testing rates, but over three quarters of patients who had not yet been screened had no intention of getting tested for CRC, despite having a medical home.
Gamma-hydroxybutyrate reduces both withdrawal syndrome and hypercortisolism in severe abstinent alcoholics: an open study vs. diazepam.

In 42 alcoholic inpatients we performed an open randomized study to compare the effects of diazepam and gamma-hydroxybutyrate (GHB) on the suppression of severe alcohol withdrawal syndrome and hypercortisolism. Both diazepam (.5 mg/kg bodyweight, q.i.d.) and GHB (50 mg/kg bodyweight, q.i.d.) were orally administered for three weeks. During all study period, GHB was more able than diazepam in reducing both withdrawal syndrome and hypercortisolism. These effects were evident during the first week of treatment and persisted throughout the study period. The results confirm a strict correlation between high levels of plasma cortisol and alcohol withdrawal symptoms and they show a slight superiority of GHB over diazepam in the suppression of both ethanol withdrawal and hypercortisolism. Taken together, our data suggest that GHB may act as potent anti-withdrawal agent in severe abstinent alcoholics.
Patient-specific computed tomography based instrumentation in total knee arthroplasty: a prospective randomized controlled study

The aim of this study was to compare radiological results of total knee arthroplasties (TKAs) performed with patient-specific computed tomography (CT)-based instrumentation and conventional technique. The main study hypothesis was that CT-based patient-specific instrumentation (PSI) increases the accuracy of TKA. A prospective, randomized controlled trial was carried out between January and December 2011. A group of 112 patients who met the inclusion and exclusion criteria were enrolled in this study and randomly assigned to an experimental or control group. The experimental group comprised 52 patients operated on with the aid of the Signature™ CT-based implant positioning system. The control group consisted of 60 patients operated on using conventional instrumentation. The radiographic evaluation of implant positioning and overall coronal alignment was performed 12 months after the surgery by using standing anteroposterior radiographs of the entire lower limb and standard lateral radiographs. Of the 112 patients initially enrolled for the study, 95 were included in the subsequent analyses. There were no statistically significant differences between groups in respect to coronal and sagittal component positioning and overall coronal alignment, except for frontal tibial component positioning. For this parameter, better results were obtained in the control group, with borderline statistical significance. Our study did not reveal superiority of the CT-based PSI system over conventional instrumentation. Further high-quality investigations of patient-specific systems are absolutely indispensable to assess their utility for TKA. In our opinion, the surgeon applying PSI technology is required to have advanced knowledge and considerable experience with the conventional method.