nils-herrmann/clean_scirepeval huggingface dataset:
Inhibition of the hedgehog pathway in advanced basal-cell carcinoma.

Mutations in hedgehog pathway genes, primarily genes encoding patched homologue 1 (PTCH1) and smoothened homologue (SMO), occur in basal-cell carcinoma. In a phase 1 clinical trial, we assessed the safety and pharmacokinetics of GDC-0449, a small-molecule inhibitor of SMO, and responses of metastatic or locally advanced basal-cell carcinoma to the drug.



We selected 33 patients with metastatic or locally advanced basal-cell carcinoma to receive oral GDC-0449 at one of three doses; 17 patients received 150 mg per day, 15 patients received 270 mg per day, and 1 patient received 540 mg per day. We assessed tumor responses with the use of Response Evaluation Criteria in Solid Tumors (RECIST), physical examination, or both. Molecular aspects of the tumors were examined.



The median duration of the study treatment was 9.8 months. Of the 33 patients, 18 had an objective response to GDC-0449, according to assessment on imaging (7 patients), physical examination (10 patients), or both (1 patient). Of the patients who had a response, 2 had a complete response and 16 had a partial response. The other 15 patients had either stable disease (11 patients) or progressive disease (4 patients). Eight grade 3 adverse events that were deemed to be possibly related to the study drug were reported in six patients, including four with fatigue, two with hyponatremia, one with muscle spasm, and one with atrial fibrillation. One grade 4 event, asymptomatic hyponatremia, was judged to be unrelated to GDC-0449. One patient withdrew from the study because of adverse events. We found evidence of hedgehog signaling in tumors that responded to the treatment.



GDC-0449, an orally active small molecule that targets the hedgehog pathway, appears to have antitumor activity in locally advanced or metastatic basal-cell carcinoma.
The ketogenic diet for the treatment of childhood epilepsy: a randomised controlled trial

The ketogenic diet has been widely and successfully used to treat children with drug-resistant epilepsy since the 1920s. The aim of this study was to test the efficacy of the ketogenic diet in a randomised controlled trial.



145 children aged between 2 and 16 years who had at least daily seizures (or more than seven seizures per week), had failed to respond to at least two antiepileptic drugs, and had not been treated previously with the ketogenic diet participated in a randomised controlled trial of its efficacy to control seizures. Enrolment for the trial ran between December, 2001, and July, 2006. Children were seen at one of two hospital centres or a residential centre for young people with epilepsy. Children were randomly assigned to receive a ketogenic diet, either immediately or after a 3-month delay, with no other changes to treatment (control group). Neither the family nor investigators were blinded to the group assignment. Early withdrawals were recorded, and seizure frequency on the diet was assessed after 3 months and compared with that of the controls. The primary endpoint was a reduction in seizures; analysis was intention to treat. Tolerability of the diet was assessed by questionnaire at 3 months. 
73 children were assigned to the ketogenic diet and 72 children to the control group. Data from 103 children were available for analysis: 54 on the ketogenic diet and 49 controls. Of those who did not complete the trial, 16 children did not receive their intervention, 16 did not provide adequate data, and ten withdrew from the treatment before the 3-month review, six because of intolerance. After 3 months, the mean percentage of baseline seizures was significantly lower in the diet group than in the controls (62.0%vs 136.9%, 75% decrease, 95% CI 42.4-107.4%; p<0.0001). 28 children (38%) in the diet group had greater than 50% seizure reduction compared with four (6%) controls (p<0.0001), and five children (7%) in the diet group had greater than 90% seizure reduction compared with no controls (p=0.0582). There was no significant difference in the efficacy of the treatment between symptomatic generalised or symptomatic focal syndromes. The most frequent side-effects reported at 3-month review were constipation, vomiting, lack of energy, and hunger.



The results from this trial of the ketogenic diet support its use in children with treatment-intractable epilepsy.



HSA Charitable Trust; Smiths Charity;
When, Where and How Osteoporosis-Associated Fractures Occur: An Analysis from the Global Longitudinal Study of Osteoporosis in Women (GLOW)

To examine when, where and how fractures occur in postmenopausal women.



We analyzed data from the Global Longitudinal Study of Osteoporosis in Women (GLOW), including women aged ≥55 years from the United States of America, Canada, Australia and seven European countries. Women completed questionnaires including fracture data at baseline and years 1, 2 and 3.



Among 60,393 postmenopausal women, 4122 incident fractures were reported (86% non-hip, non-vertebral [NHNV], 8% presumably clinical vertebral and 6% hip). Hip fractures were more likely to occur in spring, with little seasonal variation for NHNV or spine fractures. Hip fractures occurred equally inside or outside the home, whereas 65% of NHNV fractures occurred outside and 61% of vertebral fractures occurred inside the home. Falls preceded 68-86% of NHNV and 68-83% of hip fractures among women aged ≤64 to ≥85 years, increasing with age. About 45% of vertebral fractures were associated with falls in all age groups except those ≥85 years, when only 24% occurred after falling.



In this multi-national cohort, fractures occurred throughout the year, with only hip fracture having a seasonal variation, with a higher proportion in spring. Hip fractures occurred equally within and outside the home, spine fractures more often in the home, and NHNV fractures outside the home. Falls were a proximate cause of most hip and NHNV fractures. Postmenopausal women at risk for fracture need counseling about reducing potentially modifiable fracture risk factors, particularly falls both inside and outside the home and during all seasons of the year.
Xanthogranuloma of the sellar region diagnosed by frozen section

Xanthogranuloma (XG) of the sellar region is uncommon and is difficult to diagnose based on intraoperative frozen sections. This study is a case presentation and review of the literature, highlighting the need to explore underlying diseases in order to guarantee an accurate patient diagnosis. Herein, we presented the case of a 43-year-old woman who was afflicted with xanthogranuloma of the sellar region; the patient had a history of headache and lengthened menstrual cycles over the 6 months prior to presentation. Endocrinology tests revealed that the patient's levels of prolactin were high and the MRI of the patient showed a clearly defined sellar mass. As a result, the patient was considered to have prolactinoma prior to undergoing surgery. The tumor was completely removed using a transsphenoidal approach, and intraoperative frozen section revealed histology similar to xanthogranuloma. When the tumor was removed by surgical operation, the patient's visual field defects and headache were relieved. Although intraoperative frozen section should provide some guidance with regard to the diagnosis, a pathological study is conducted to confirm the actual diagnosis.
Polymyxin-B hemoperfusion inactivates circulating proapoptotic factors

To test the hypothesis that extracorporeal therapy with polymyxin B (PMX-B) may prevent Gram-negative sepsis-induced acute renal failure (ARF) by reducing the activity of proapoptotic circulating factors. Medical-Surgical Intensive Care Units. Sixteen patients with Gram-negative sepsis were randomized to receive standard care (Surviving Sepsis Campaign guidelines) or standard care plus extracorporeal therapy with PMX-B. Cell viability, apoptosis, polarity, morphogenesis, and epithelial integrity were evaluated in cultured tubular cells and glomerular podocytes incubated with plasma from patients of both groups. Renal function was evaluated as SOFA and RIFLE scores, proteinuria, and tubular enzymes. A significant decrease of plasma-induced proapoptotic activity was observed after PMX-B treatment on cultured renal cells. SOFA and RIFLE scores, proteinuria, and urine tubular enzymes were all significantly reduced after PMX-B treatment. Loss of plasma-induced polarity and permeability of cell cultures was abrogated with the plasma of patients treated with PMX-B. These results were associated to a preserved expression of molecules crucial for tubular and glomerular functional integrity. Extracorporeal therapy with PMX-B reduces the proapoptotic activity of the plasma of septic patients on cultured renal cells. These data confirm the role of apoptosis in the development of sepsis-related ARF.
Serum hyaluronan in patients with multiple myeloma: correlation with survival and Ig concentration.

Serum from 386 myeloma patients were analyzed for serum hyaluronan (HYA) at diagnosis. Median age was 68 years (range, 32 to 87 years). The distribution of Ig classes was typical (58% IgG, 21% IgA, 1% IgD, and 20% light chain disease). The patients comprised 58% in stage III, 33% in stage II, and 9% in stage I. The majority (82%) had HYA values within an intermediate range (10 to 120 micrograms/L), 13% had high values (>120 micrograms/L), and 5% had abnormally low values (0 to 9 micrograms/L). For the first time, a patient group with abnormally low HYA serum values is reported. An inverse correlation between survival and HYA serum level was found (P =.015). When tested separately, patients with abnormally low or high HYA values had significantly shorter median survival (21.1 and 19.7 months, respectively) than those with an intermediate HYA concentration (32. 6 months; P =.005). Patients with abnormally low or high HYA levels had more advanced disease as judged by staging and biochemical markers. Interestingly, there was an inverse correlation between the HYA value and the M-component concentration in serum. Fifty percent of patients with abnormally low HYA values had IgA myelomas. In conclusion, the serum concentration of HYA may be of prognostic value in selected cases of multiple myeloma. Further studies will be performed to elucidate possible explanations for our findings, especially those related to the HYA cell surface binding proteins.
Throbbing pain is related to Queckenstedt's test effect in migraine patients.

The Queckenstedt's (Q)-test can aggravate headache intensity during migraine attacks (Q-test effect). The objective of this study was to delineate the Q-test effect in patients experiencing migraine attacks. We performed a 30-s Q- and a sham test on 39 patients with acute migraine attacks in both supine and sitting positions. Headache intensities during and 30 s after the Q- or sham tests were recorded on a 0-10 verbal scale. Brushing allodynia (BA) was recorded after using a gauze-brushing test over the patient's face and forearms. The Q- but not the sham test aggravated headache intensity in both sitting and supine positions. The presence of throbbing pain and higher pain intensities was associated with the Q-test effect in the supine position. However, the presence or absence of BA was not correlated. We concluded that the Q-test effect is likely to be related to peripheral sensitization of the meninges but not central sensitization. The Q-test effect may be used as an objective marker for peripheral sensitization.
Comparative efficacy of once-daily ciclesonide and budesonide in the treatment of persistent asthma

ee front matter & 2005 med.2005.11.030 ng author.  The aim of this study was to compare the efficacy and safety of oncedaily ciclesonide, a new-generation, on-site-activated, inhaled corticosteroid, with once-daily budesonide in persistent asthma.  Eligible patients requiring budesonide or equivalent 320–640 mg (ex-mouthpiece, equivalent to 400–800 mg; Turbohaler) daily entered a 2-week baseline, and then a 2to 4-week pretreatment period (budesonide 1280 mg/day; exmouthpiece, equivalent to 1600 mg/day). Patients with an increase in forced expiratory volume in 1 s (FEV1) of X7% or X0.15 L were randomised to ciclesonide 320 mg (ex-actuator, equivalent to 400 mg ex-valve) via a hydrofluoroalkane-metered dose inhaler (HFA-MDI) without a spacer or budesonide 320 mg once daily in the morning for 12 weeks. Change in FEV1 was the primary endpoint.  In all, 359 patients were randomised. The FEV1 and forced vital capacity (FVC) decreased by 0.18 and 0.12 L, respectively, in the ciclesonide group, and by 0.23 and 0.21 L in the budesonide group. For FEV1, ciclesonide was noninferior and numerically superior to budesonide. For FVC, ciclesonide was statistically superior to budesonide (P 1⁄4 0.010). Asthma symptom scores were comparable; the median percentage of symptom-free days was significantly higher for ciclesonide (43.6%) versus budesonide (25.8%) (P 1⁄4 0.017). Rescue medication use decreased significantly only for ciclesonide patients (P 1⁄4 0.009). Frequency of adverse events was low in both groups.
RETRACTED ARTICLE: Total knee arthroplasty performed with either a mini-subvastus or a standard approach: a prospective randomized controlled study with a minimum follow-up of 2 years

There is currently a trend toward minimally invasive total knee arthroplasty (TKA) to decrease the morbidity related to the standard approach. The aim of our study was to clarify whether the mini-subvastus surgical had an advantage over the standard in term of pain level, blood loss, and postoperative recovery, whether the mini-subvastus surgical was prone to radiographic malalignment, prolonged operative time, and increased complications. In a prospective randomized study, we compared the clinical and radiological results of primary TKA using a mini-subvastus approach or a standard approach in 68 patients. The mini-subvastus approach was used on 35 patients (group I) and the standard approach on 33 patients (group II). The mean follow-up was 28 months (range 24–36 months). Patients in group I had less blood loss and better visual analogue scale score at 1 day postoperatively. They achieved active straight leg raise earlier and underwent less lateral retinacular releases. The mean Knee Society function score, Oxford knee score, and range of movement were significantly better in group I up to 9 months after surgery (all, p < 0.05). However, there were no significant differences in these parameters between the groups at final follow-up. Reduced access and visibility in group I prolonged tourniquet time by an average of 22 min and resulted in five technical errors on radiographic evaluation. Patients can receive marked but temporary benefits from the mini-subvastus technique, with a definite cost: that of component malposition and prolongation of operative time.
A phase I/II dose-escalation trial of vitamin D3 and calcium in multiple sclerosis.

Low vitamin D status has been associated with multiple sclerosis (MS) prevalence and risk, but the therapeutic potential of vitamin D in established MS has not been explored. Our aim was to assess the tolerability of high-dose oral vitamin D and its impact on biochemical, immunologic, and clinical outcomes in patients with MS prospectively.



An open-label randomized prospective controlled 52-week trial matched patients with MS for demographic and disease characteristics, with randomization to treatment or control groups. Treatment patients received escalating vitamin D doses up to 40,000 IU/day over 28 weeks to raise serum 25-hydroxyvitamin D [25(OH)D] rapidly and assess tolerability, followed by 10,000 IU/day (12 weeks), and further downtitrated to 0 IU/day. Calcium (1,200 mg/day) was given throughout the trial. Primary endpoints were mean change in serum calcium at each vitamin D dose and a comparison of serum calcium between groups. Secondary endpoints included 25(OH)D and other biochemical measures, immunologic biomarkers, relapse events, and Expanded Disability Status Scale (EDSS) score.



Forty-nine patients (25 treatment, 24 control) were enrolled [mean age 40.5 years, EDSS 1.34, and 25(OH)D 78 nmol/L]. All calcium-related measures within and between groups were normal. Despite a mean peak 25(OH)D of 413 nmol/L, no significant adverse events occurred. Although there may have been confounding variables in clinical outcomes, treatment group patients appeared to have fewer relapse events and a persistent reduction in T-cell proliferation compared to controls.



High-dose vitamin D (approximately 10,000 IU/day) in multiple sclerosis is safe, with evidence of immunomodulatory effects.



This trial provides Class II evidence that high-dose vitamin D use for 52 weeks in patients with multiple sclerosis does not significantly increase serum calcium levels when compared to patients not on high-dose supplementation. The trial, however, lacked statistical precision and the design requirements to adequately assess changes in clinical disease measures (relapses and Expanded Disability Status Scale scores), providing only Class level IV evidence for these outcomes.
Consequence of cerebral embolism after transcatheter aortic valve implantation compared with contemporary surgical aortic valve replacement: effect on health-related quality of life.

Incidence of cerebral microinfarcts is higher after transcatheter aortic valve implantation (TAVI) compared with surgical aortic valve replacement (SAVR). It is unknown whether these lesions persist and what direct impact they have on health-related quality of life. The objective was to identify predictors of cerebral microinfarction and measure their effect on health-related quality of life during 6 months after TAVI when compared with SAVR.



Cerebral MRI was conducted at baseline, post procedure, and 6 months using diffusion-weighted imaging. Health-related quality of life was measured at baseline, 30 days, and 6 months with short form-12 health outcomes and EuroQol 5 dimensions questionnaires. One hundred eleven patients (TAVI, n=71; SAVR, n=40) were studied. The incidence (54 [77%] versus 17 [43%]; P=0.001) and number (3.4±4.9 versus 1.2±1.8; P=0.001) of new microinfarcts were greater after TAVI than after SAVR. The total volume per microinfarct was smaller in TAVI than in SAVR (0.23±0.24 versus 0.76±1.8 mL; P=0.04). The strongest associations for microinfarction were: TAVI (arch atheroma grade: r=0.46; P=0.0001) and SAVR (concomitant coronary artery bypass grafting: r=-0.33; P=0.03). Physical component score in TAVI increased after 30 days (32.1±6.6 versus 38.9±7.0; P<0.0001) and 6 months (40.4±9.3; P<0.0001); the improvement occurred later in SAVR (baseline: 34.9±10.6; 30 days: 35.9±10.2; 6 months: 42.8±11.2; P<0.001). After TAVI, there were no differences in the short form-12 health outcome scores according to the presence or size of new cerebral infarction.



Cerebral microinfarctions are more common after TAVI compared with SAVR but seem to have no negative effect on early (30 days) or medium term (6 months) health-related quality of life. Aortic atheroma (TAVI) and concomitant coronary artery bypass grafting (SAVR) are independent risk factors for cerebral microinfarction.
A three year comparative multicenter study of auranofin (AF) and gold sodium thiomalate (GST) in the treatment of rheumatoid arthritis (RA)

After some open trials had shown a promising efficacy and side-effect profile of the oral gold compound auranofin, we considered it worthwhile to conduct a double-blind comparison of auranofin (AF) and gold sodium thiomalate (GST) in patients with active rheumatoid arthritis. One Austrian and four German centres (Table I) participated in the study, which was conducted from 1979 to 1983. It has to be pointed out that originally the trial was planned only for one year but during this first year it was decided to continue the study after the double-blind phase of 48 weeks as an open trial. Investigators were allowed to either continue patients on their active study medication for one more year, switch patients from GST to auranofin or withdraw the patients from the protocol. At the end of the second year investigators were asked to continue the open phase of the trial for one more year, but to switch patients from GST to AF if possible.
Granulocyte-macrophage colony-stimulating factor alone or with dacarbazine in metastatic melanoma: a randomized phase II trial

The potential antitumoural effect of granulocyte-macrophage colony-stimulating factor (GM-CSF) led us to evaluate GM-CSF alone or with dacarbazine (DTIC) in metastatic melanoma in first line randomized phase II. Treatment was arm A: GM-CSF: 5 μg kg–1, bid, 14 consecutive days every 21 days and arm B: GM-CSF: 5 μg kg–1, bid, day 2 to day 19 every 21 days and DTIC: 800 mg m–2, day 1 of each cycle. 32 patients (pts) were included, 15 pts in arm A and 17 in arm B. All pts had visceral metastatic sites. 9 had only one metastatic site. The median number of cycles given was 2 in arm A and 3 in arm B. 100% and 89.4% of the planned dose of GM-CSF was given in arm A and arm B respectively. No objective response was obtained. 19 pts experienced at least WHO grade 3 toxicity. All pts had fever, 29 had a decrease in performance status and 23 had pain. Grade 3 toxicity were fever (38.7%), decrease in performance status (32.3%), pain (19.4%) and dyspnoea (12.5%). In this study, GM-CSF alone or in association with DTIC did not induce any antitumoural activity with subsequent toxicity.
Correlation between tremor parameters.

The relationship between clinically scored tremor and electromyographic measurements of tremor amplitude is not clear and few reports have examined correlations between different tremor parameters. The aim of this study was to evaluate the correlations between different tremor parameters, clinical tremor scoring, age and disease duration. A total of 525 patients with different types of tremor were included in this study. Tremor in various limb positions was graded according to the Webster Tremor Scale. Surface electromyographic recordings of the limb found, in each position, to be most involved were performed in all the patients. The Spearman rank correlation coefficient was used to analyse the relationship between clinical and electromyographic parameters, while the Pearson correlation coefficient was used to analyse the relationship between the electromyographic parameters. Our results revealed moderate correlation between tremor amplitude as measured by electromyography and Webster tremor scores. The correlation between different tremor parameters revealed that low frequency tremors have higher amplitude, and longer burst duration, interval between bursts and missing interval. As the disease progresses, the tremor amplitude increases, while the frequency decreases. A strong positive correlation emerged between corresponding tremor parameters in different limb positions. This suggests that the tremor in all limb positions is generated by the same oscillator. In conclusion, a good correlation was found between clinically scored tremor and EMG measurements of tremor amplitude. The electromyographic examination is a useful tool for researching tremor mechanisms.