nils-herrmann/clean_scirepeval huggingface dataset:
Allopurinol improves myocardial efficiency in patients with idiopathic dilated cardiomyopathy.

Dilated cardiomyopathy is characterized by an imbalance between left ventricular performance and myocardial energy consumption. Experimental models suggest that oxidative stress resulting from increased xanthine oxidase (XO) activity contributes to this imbalance. Accordingly, we hypothesized that XO inhibition with intracoronary allopurinol improves left ventricular efficiency in patients with idiopathic dilated cardiomyopathy.



Patients (n=9; ejection fraction, 29+/-3%) were instrumented to assess myocardial oxygen consumption (MVO(2)), peak rate of rise of left ventricular pressure (dP/dt(max)), stroke work (SW), and efficiency (dP/dt(max)/MV O(2) and SW/MVO(2)) at baseline and after sequential infusions of intracoronary allopurinol (0.5, 1.0, and 1.5 mg/min, each for 15 minutes). Allopurinol caused a significant decrease in MVO(2) (peak effect, -16+/-5%; P<0.01; n=9) with no parallel decrease in dP/dt(max) or SW and no change in ventricular load. The net result was a substantial improvement in myocardial efficiency (peak effects: dP/dt(max)/MVO(2), 22+/-9%, n=9; SW/MVO(2), 40+/-17%, n=6; both P<0.05). These effects were apparent despite concomitant treatment with standard heart failure therapy, including ACE inhibitors and beta-blockers. XO and its parent enzyme xanthine dehydrogenase were more abundant in failing explanted human myocardium on immunoblot.



These findings indicate that XO activity may contribute to abnormal energy metabolism in human cardiomyopathy. By reversing the energetic inefficiency of the failing heart, pharmacological XO inhibition represents a potential novel therapeutic strategy for the treatment of human heart failure.
Effect of self-referral on bone mineral density testing and osteoporosis treatment.

Despite national guidelines recommending bone mineral density screening with dual-energy x-ray absorptiometry (DXA) in women aged 65 years and older, many women do not receive initial screening.



To determine the effectiveness of health system and patient-level interventions designed to increase appropriate DXA testing and osteoporosis treatment through (1) an invitation to self-refer for DXA (self-referral); (2) self-referral plus patient educational materials; and (3) usual care (UC, physician referral).



Parallel, group-randomized, controlled trials performed at Kaiser Permanente Northwest (KPNW) and Kaiser Permanente Georgia (KPG).



Women aged 65 years and older without a DXA in past 5 years.



DXA completion rates 90 days after intervention mailing and osteoporosis medication receipt 180 days after initial intervention mailing.



From >12,000 eligible women, those randomized to self-referral were significantly more likely to receive a DXA than UC (13.0%-24.1% self-referral vs. 4.9%-5.9% UC, P<0.05). DXA rates did not significantly increase with patient educational materials. Osteoporosis was detected in a greater proportion of self-referral women compared with UC (P<0.001). The number needed to receive an invitation to result in a DXA in KPNW and KPG regions was approximately 5 and 12, respectively. New osteoporosis prescription rates were low (0.8%-3.4%) but significantly greater among self-referral versus UC in KPNW.



DXA rates significantly improved with a mailed invitation to schedule a scan without physician referral. Providing women the opportunity to self-refer may be an effective, low-cost strategy to increase access for recommended osteoporosis screening.
A Randomized Controlled Trial for the Effectiveness of Aromatherapy in Decreasing Salivary Gland Damage following Radioactive Iodine Therapy for Differentiated Thyroid Cancer

The aim of this study was to investigate effects of aromatherapy in decreasing salivary gland damage for patients undergoing radioactive iodine (RAI) therapy with differentiated thyroid cancer (DTC).  The subjects were 71 patients with DTC. They were divided into aromatherapy group (group A, n = 35) and a control group (group B, n = 36). We blended 1.0 mL of lemon and 0.5 mL of ginger essential oils. The patients in the inhalation aromatherapy group inhaled this blend oil and those in the control group inhaled distilled water as placebo for 10 min during admission. We statistically compared salivary gland function before and after treatment between groups A and B.  In comparison with group B, the rate of change of the accumulation rate was significantly higher in the parotid glands and submandibular glands of group A (P < 0.05). In comparison with group B, a significant increase in rate of secretion change before and after treatment was noted in the bilateral parotid glands in group A (P < 0.05).  Because an amelioration of salivary gland function was observed in the present study, our results suggest the efficacy of aromatherapy in the prevention of treatment-related salivary gland disorder.
Aquaporin 5 Polymorphisms and Rate of Lung Function Decline in Chronic Obstructive Pulmonary Disease

Aquaporin-5 (AQP5) can cause mucus overproduction and lower lung function. Genetic variants in the AQP5 gene might be associated with rate of lung function decline in chronic obstructive pulmonary disease (COPD).



Five single nucleotide polymorphisms (SNPs) in AQP5 were genotyped in 429 European American individuals with COPD randomly selected from the NHLBI Lung Health Study. Mean annual decline in FEV(1) % predicted, assessed over five years, was calculated as a linear regression slope, adjusting for potential covariates and stratified by smoking status. Constructs containing the wildtype allele and risk allele of the coding SNP N228K were generated using site-directed mutagenesis, and transfected into HBE-16 (human bronchial epithelial cell line). AQP5 abundance and localization were assessed by immunoblots and confocal immunofluorescence under control, shear stress and cigarette smoke extract (CSE 10%) exposed conditions to test for differential expression or localization.



Among continuous smokers, three of the five SNPs tested showed significant associations (0.02>P>0.004) with rate of lung function decline; no associations were observed among the group of intermittent or former smokers. Haplotype tests revealed multiple association signals (0.012>P>0.0008) consistent with the single-SNP results. In HBE16 cells, shear stress and CSE led to a decrease in AQP5 abundance in the wild-type, but not in the N228K AQP5 plasmid.



Polymorphisms in AQP5 were associated with rate of lung function decline in continuous smokers with COPD. A missense mutation modulates AQP-5 expression in response to cigarette smoke extract and shear stress. These results suggest that AQP5 may be an important candidate gene for COPD.
High-resolution endoscopy and endoscopic ultrasound for evaluation of early neoplasia in Barrett’s esophagus

Endoscopic ultrasound (EUS) is useful for detecting depth of invasion and nodal involvement in patients with early Barrett’s neoplasia (EBN), precluding endoscopic management. This study aimed to determine whether the lesion morphology of the EBN shown on high-resolution endoscopy predicts EUS and histologic tumor stage. Retrospective series from two tertiary referral centers were studied. Patients with EBN referred for EUS evaluation before treatment were identified, and data were collected from endoscopies, a database, and case notes. All patients had high-resolution endoscopy followed by radial EUS. This study included 50 patients (22 men) with a median age of 69 years (interquartile range, 60–79 years). Visible lesions in the Barrett’s segment were described as Paris types 0–1 (n = 9), 0–IIb (n = 12), 0–IIa (n = 12), 0–IIa + IIc (n = 6), and 0–IIc (n = 5). Of the 50 patients, 46 (92%) had either EMR (n = 17), esophagectomy (n = 23), or both (n = 6). All 12 patients (100%) with Paris 0–IIb lesions had T0/T1 m staging on EUS confirmed with resection histology. The sensitivity for EUS T-staging for Paris classification was 71.4% for type 0–I, 100% for type 0–IIb, 83% for type 0–IIa, 66.7% for type 0–IIa + IIc, and 66.7% for type IIc. Overall, 8 (17%) of the 46 patients were understaged and 2 (4%) were overstaged. For detecting submucosal invasion, EUS had a sensitivity of 66%, a specificity of 93%, a negative predictive value of 85%, and a diagnostic accuracy of 84.4%. Submucosal invasion is detected by EUS for 26% of patients with EBN. The value of EUS staging before resection for type 0–IIb early Barrett’s cancer (flat lesions) is limited because 100% of these lesions are limited to the mucosa. For the management algorithm in this selected cohort, the use of EUS should be reconsidered.
A phase I/II trial of reduced intensity allogeneic hematopoietic cell transplant for hematologic malignancies using cladribine, thiotepa and rabbit antithymocyte globulin.

We conducted a phase I/II trial to assess the efficacy of cladribine, thiotepa and antithymocyte globulin as a reduced-intensity conditioning regimen for refractory or high-risk hematologic malignancy. The preparative regimen consisted of cladribine 5 mg/m(2)/day for 5 days, thiotepa 200 mg/m(2)/day for 3 days and ATG 3 mg/kg/day (day - 5) followed by allogeneic peripheral blood stem cell transplant. Twelve patients were transplanted from a human leukocyte antigen (HLA) matched family member. Two patients were treated at dose level I but both experienced grade IV dose limiting toxicities, and therefore the thiotepa dose was reduced to 133 mg/m(2)/day (dose level II). Only two of the next six patients experienced dose limiting toxicities. Median age was 46 years. At dose level II, the median time to neutrophil and platelet engraftment was 17 and 20 days, respectively. The incidence of acute and chronic graft-versus-host disease (GVHD) was 40% and 30%, respectively. Day + 100 non-relapse mortality was 0% and at 1 year was 20%. Median overall survival (OS) was 42 months and 2-year OS was 70%. Median progression-free survival (PFS) was 11 months and 2-year PFS was 40%. We conclude that the reduced-intensity conditioning regimen of cladribine, thiotepa and ATG achieved excellent donor chimerism with acceptable toxicity.
Evaluation of vertebral fracture assessment by dual X-ray absorptiometry in a multicenter setting

The utility of vertebral fracture assessment (VFA) by DXA to detect prevalent vertebral fracture in a multicenter setting was investigated by comparison to conventional radiography. While limited by lower image quality, overall performance of VFA was good but had a tendency to miss mild prevalent fractures. In osteoporosis clinical trials standardized spine radiographs are used to detect vertebral fractures as a study endpoint. Lateral spine imaging with dual X-ray absorptiometry (DXA) scanners, known as vertebral fracture assessment (VFA) by DXA, presents a potential alternative to conventional radiography with lower radiation dose and greater patient convenience. We investigated in a multicenter setting the ability of VFA to detect fractures in comparison with conventional radiography. The study examined 203 postmenopausal women who had imaging of the spine by DXA and radiography. Three radiologists experienced in vertebral fracture assessment independently read the VFA scans and radiographs using the Genant semiquantitative method on two occasions. Analyzing the data from all readable vertebrae, the kappa statistic, sensitivity, and specificity ranged from 0.64–0.77, 0.65–0.84, and 0.97–0.98, respectively. Considering only moderate and severe fractures improved the kappa statistic (0.80–0.91) and sensitivity (0.70–0.86). While image quality of VFA is inferior to radiography, the detection of vertebral fractures using visual scoring is feasible. However, VFA underperformed due to unreadable vertebrae and reduced sensitivity for mild fractures. Nevertheless, VFA correctly identified most moderate and severe vertebral fractures. Despite this limitation, VFA by DXA provides an important tool for clinical research.
Effectiveness and cost-effectiveness of web-based treatment for phobic outpatients on a waiting list for psychotherapy: protocol of a randomised controlled trial

Phobic disorders are highly prevalent and constitute a considerable burden for patients and society. As patients wait for face-to-face psychotherapy for phobic disorders in outpatient clinics, this time can be used for guided self-help interventions. The aim of this study is to investigate a five week internet-based guided self-help programme of exposure therapy in terms of clinical effectiveness and impact on speed of recovery in psychiatric outpatients, as well as the cost-effectiveness of this pre-treatment waiting list intervention.



A randomised controlled trial will be conducted among 244 Dutch adult patients recruited from waiting lists of outpatient clinics for face-to-face psychotherapy for phobic disorders. Patients suffering from at least one DSM-IV classified phobic disorder (social phobia, agoraphobia or specific phobia) are randomly allocated (at a 1:1 ratio) to either a five-week internet-based guided self-help program followed by face-to-face psychotherapy, or a control group followed by face-to-face psychotherapy. Waiting list status and duration are unchanged and actual need for further treatment is evaluated prior to face-to-face psychotherapy. Clinical and economic self-assessment measurements take place at baseline, post-test (five weeks after baseline) and at 3, 6, 9 and 12 months after baseline.



Offering pre-treatment internet-based guided self-help efficiently uses time otherwise lost on a waiting list and may increase patient satisfaction. Patients are expected to need fewer face-to-face sessions, reducing total treatment cost and increasing speed of recovery. Internet-delivered treatment for phobias may be a valuable addition to psychotherapy as demand for outpatient treatment increases while budgets decrease.
Peripheral blood mono-nuclear cells implantation in patients with peripheral arterial disease: a pilot study for clinical and biochemical outcome of neoangiogenesis

Substantial progresses in the management of peripheral arterial disease (PAD) have been made in the past two decades. Progress in the understanding of the endothelial-platelet interaction during health and disease state has resulted in better antiplatelet drugs that can prevent platelet aggregation, activation and thrombosis during angioplasty and stenting. A role in physiological and pathological angiogenesis in adults has been recently shown in bone marrow-derived circulating endothelial progenitors (BM-DCEPs) identified in the peripheral blood. These findings have paved the way for the development of therapeutic neovascularization techniques using endothelial progenitors.



This pilot study includes five patients, aged 60 to 75, with a history of claudication and recruited from September 2010 to February 2011 at the A.O.U. Federico II of Naples.PBMNCs have been implanted three times in the limb with the worst ABI value in all the patients included in the study.The clinical follow up was performed during the subsequent 12 months from the beginning of the treatment.



In four patients there was a regression of ulcerative lesions.One patient's condition improved after the first implantation but later did not respond to the further treatments.All patients achieved a pain relief as judged by the numeric pain scale. Pain relief remained satisfactory in three patients for one year. Pain gradually returned to the pre-treatment level in two patients.All patients referred an ameliorating in their quality of life expressed even by an improvement in claudication free walking distance.These improvements are reflected also by intra-arterial digital subtraction angiography (IADSA) that shows an improvement of arterial vascularization.



The data from this study suggest an efficacy of BM-DCEPs implantation in terms of improvement of the vascularization and quality of life in patients affected by Peripheral Arterial Disease. Nevertheless a double-blind placebo-controlled study is needed to confirm our findings.
Obesity might be a good prognosis factor for COPD patients using domiciliary noninvasive mechanical ventilation

Cachexia is known to be a deteriorating factor for survival of patients with chronic obstructive pulmonary disease (COPD), but data related to obesity are limited. We observed that obese patients with COPD prescribed long-term noninvasive mechanical ventilation (NIMV) had better survival rate compared to nonobese patients. Therefore, we conducted a retrospective observational cohort study. Archives of Thoracic Diseases Training Hospital were sought between 2008 and 2013. All the subjects were prescribed domiciliary NIMV for chronic respiratory failure secondary to COPD. Subjects were grouped according to their body mass index (BMI). The first group consisted of subjects with BMI between 20 and 30 kg/m(2), and the second group consisted of subjects with BMI >30 kg/m(2). Data obtained at the first month's visit for the following parameters were recorded: age, sex, comorbid diseases, smoking history, pulmonary function test, 6-minute walk test (6-MWT), and arterial blood gas analysis. Hospital admissions were recorded before and after the domiciliary NIMV usage. Mortality rate was searched from the electronic database. Overall, 118 subjects were enrolled. Thirty-eight subjects had BMI between 20 and 30 kg/m(2), while 80 subjects had BMI >30 kg/m(2). The mean age was 65.8±9.4 years, and 81% were male. The median follow-up time was 26 months and mortality rates were 32% and 34% for obese and nonobese subjects (P=0.67). Improvement in 6-MWT was protective against mortality. In conclusion, survival of obese patients with COPD using domiciliary NIMV was found to be better than those of nonobese patients, and the improvement in 6-MWT in such patients was found to be related to a better survival.
Long-term influence of insulin dependent diabetes mellitus on refraction and its components: a population based twin study.

To study whether refraction of the eye, or some of its components is influenced by duration of insulin dependent diabetes mellitus.



From the young cohort of the population based Danish Twin Register, containing 20,888 twin pairs born between 1953 and 1982, all twin pairs having one or both partners affected with IDDM were searched. Autorefraction, autokeratometry, and ultrasonic biometric measurements were carried out on 45 twin pairs: 16 monozygotic (MZ) twin pairs, 14 dizygotic twin pairs of same sex (DZss), and 15 dizygotic twin pairs of opposite sex (DZos). To obtain an estimate of the influence of duration of diabetes, the intrapair differences in duration of diabetes were correlated with intrapair differences in refraction and each of its components.



Refraction was statistically significantly negatively correlated with duration of diabetes in the DZss group, and axial length correspondingly positively correlated. Surprisingly, refraction and axial length in the MZ group, adjusted for confounding factors, were correlated with diabetes duration in the opposite direction than in the DZss group, although not reaching statistical significance. Lens thickness was statistically significantly positively correlated with duration of diabetes in both MZ and DZ twins. Anterior chamber depth was negatively correlated with duration of diabetes in all the zygosity groups.



Studies of relations between refraction and duration of diabetes show diverging results. In the MZ group, a tendency to reduced axial length and corresponding hyperopia with increasing duration of diabetes was found. However, in the DZ group of same sex the opposite tendency was found. Increasing lens thickness and decreasing anterior chamber depth with increasing duration of diabetes have been confirmed in this study.
Validation of the Malnutrition Universal Screening Tool (MUST) in cancer.

In the present study, we aimed to validate the Malnutrition Universal Screening Tool (MUST) for routine nutritional screening in the radiation oncology setting, thus enabling timely and adequate referrals of patients at risk for individualised or advanced intervention. Towards this objective, we conducted a prospective cross-sectional study in 450 non-selected cancer patients (18-95 years) referred for radiotherapy. The following were the nutritional parameters: BMI (categorised by WHO's age/sex criteria), weight loss >5 % in the previous 3-6 months, Patient-Generated Subjective Global Assessment (PG-SGA - validated/specific for oncology) and nutritional risk by MUST. Sensitivity, specificity, predictive values and concordance were calculated to validate MUST v. PG-SGA and compare single parameters v. PG-SGA/MUST. BMI v. PG-SGA showed a negligible capacity to detect undernutrition: 0.27 sensitivity, 0.23 specificity, 0.35 positive predictive value and 0.31 negative predictive value. Conversely, percentage weight loss v. PG-SGA was highly effective: 0.76 sensitivity, 0.85 specificity, 0.79 positive predictive value and 0.85 negative predictive value. MUST v. PG-SGA successfully detected patients at risk: 0.80 sensitivity, 0.89 specificity, 0.87 positive predictive value and 1.0 negative predictive value; percentage weight loss v. MUST proved able to identify patients likely to be at risk: 0.85 sensitivity, 0.91 specificity, 0.90 positive predictive value and 1.0 negative predictive value. This is the first study in the radiation oncology setting to validate MUST: a simple and quick method applicable by any health professional, with a high validity for early screening, ideally to antedate a comprehensive nutritional assessment and guide for intervention. In this study, percentage weight loss in the previous 3-6 months does seem valid to predict nutritional risk, and may be the minimum in a busy routine.
Anti-CD20 therapy in patients with rheumatoid arthritis: predictors of response and B cell subset regeneration after repeated treatment.

B cell depletion with the anti-CD20 antibody rituximab has proven efficacy in patients with rheumatoid arthritis (RA). The effects on B cell homeostasis after repeated treatments and the relationship of certain B cell subsets to clinical response or relapse are currently not known.



In this open-label study, 17 patients with RA refractory to standard therapy were treated with 1 cycle of rituximab. Of these 17 patients, 11 received a second cycle of rituximab therapy. Immunophenotyping was performed before therapy and during B cell recovery.



Twelve of 17 patients showed a good European League Against Rheumatism response after receiving 1 cycle of rituximab therapy. At the time of B cell recovery, the IgD+,CD27+ memory B cell subset was significantly larger (P = 0.019) in the nonresponder group. Within the group of 12 responders, 6 patients, whose disease was characterized by a significantly higher proportion of overall CD27+ memory B cells before therapy, experienced an early relapse (weeks 24-40 posttreatment). Eleven patients were re-treated, again resulting in a good clinical response. B cell reconstitution followed a similar pattern after each cycle. The early reconstitution phase was characterized by immature CD38++,IgD+,CD10+ B cells, whereas the number of naive B cells increased continuously thereafter. The number of memory B cells was still reduced at the time of the second depletion but recovered to levels similar to those following the first cycle of therapy.



Data derived from repeated B lymphocyte depletion with rituximab in patients with RA suggest that analysis of certain memory B cell subsets provides information on efficacy, response, and late as well as early relapse, consistent with the conclusion that targeting memory B cells is a key to its mechanism of action.