nils-herrmann/clean_scirepeval huggingface dataset:
Long-term effects of intermittent androgen suppression therapy on lean and fat mass: a 33-month prospective study

To examine changes to whole body and regional lean mass (LM) and fat mass (FM) over 33 months of intermittent androgen suppression therapy (Phase II cohort study of 72 prostate cancer patients without metastatic bone disease. Patients received flutamide 250 mg tid and leuprolide 22.5 mg three monthly depot for the 9-month initial treatment phase (iTREAT), at which point patients ceased therapy providing PSA <4 ng ml−1 with continued monitoring for further 2 years (POST). AST was recommenced when PSA exceeded pretreatment level or ⩾20 ng ml−1. Body composition was assessed using dual energy X-ray absorptiometry at baseline, completion of treatment phase, and 1 and 2 years post treatment phase (months 21 and 33).Results:LM decreased by 1.3 kg and FM increased by 2.3 kg (P<0.001) following iTREAT. During the POST period, there were no further adverse effects on LM or FM, but also no recovery to pretreatment levels. Patients who failed to recover testosterone by month 33 experienced a significant increase in FM compared with those who recovered eugonadal levels of testosterone (10 nmol ml−1; P=0.019). Change in testosterone was moderately correlated to changes in % FM (r=−0.314, P<0.028) and LM (r=0.300, P<0.036) during POST phase. Waist circumference progressively increased over time and by 2 years, POST had not recovered to baseline levels.Loss of LM and gain in FM during the 9-month iTREAT was not reversed during 2-year POST, although further deterioration was not observed. Subgroup analysis identified those recovering testosterone showed some body composition improvements. These findings suggest potential benefits of IAST, where testosterone levels are able to recover, to reduce the ongoing adverse effects on body composition, such as the acceleration of sarcopenia and risks associated with metabolic disease.
Intraarterial chemotherapy as an adjuvant treatment in locally advanced gastric cancer

D2 gastrectomy has improved survival in gastric cancer. Adjuvant intravenous chemotherapy, radiotherapy, or multimodal therapy has failed to demonstrate improved survival. The results of intraarterial chemotherapy (IARC) as an adjuvant have been encouraging in a few studies. A prospective randomized trial was designed to evaluate the toxicity and survival in locally advanced gastric cancer using IARC as an adjuvant after potentially curative gastrectomy. Forty patients with locally advanced gastric cancer were randomly selected to undergo either potentially curative gastrectomy and receive IARC (study group) or gastrectomy only (control group). Clinical and histopathologic data were analyzed and the toxicity related to IARC was recorded. The groups were comparable (p>0.05). Three patients in the study group had minor toxicity. Five-year survival rate for the study and the control group was 52 and 54%, respectively (p>0.05). Mean survival for the study and the control group was 50±8 and 62±10 months, respectively (p>0.05). The number of recurrences and the failure sites were comparable (p>0.05). Intraarterial chemotherapy can be safely applied to gastric cancer patients. As proposed by the protocol, the method cannot be recommended as an adjuvant treatment for locally advanced tumors because it appears that there is no survival benefit compared to potentially curative gastrectomy alone.
Cerebral ischemia in aneurysmal subarachnoid hemorrhage: a correlative microdialysis-PET study.

Cerebral microdialysis (MD) is discussed as a technique for detection of cerebral ischemia in subarachnoid hemorrhage; however, clinical data on cerebral blood flow (CBF) are limited in these patients. The main objective of this study was to investigate whether pathological MD parameters reflect a reduced regional CBF (rCBF) determined by 15O-H2O PET.



Thirteen subarachnoid hemorrhage patients (age, 48.7+/-15.0 years; World Federation of Neurological Surgeons grade 1 to 5) were studied. Extracellular glucose, lactate, lactate/pyruvate (L/P) ratio, glutamate, and glycerol levels were analyzed hourly. rCBF was determined in the volume of interest of the MD catheter and all vascular territories. MD values were correlated to rCBF on the day of PET. Then, MD concentrations of asymptomatic versus ischemic phases (3-day medians) were analyzed.



In symptomatic patients (n=10), rCBF was significantly lower compared with controls (n=3, P=0.048). Glutamate correlated best with rCBF (r=-0.66; P=0.014), followed by glycerol (r=-0.62; P=0.021). The L/P ratio was most sensitive (0.82) and specific (1.0) in indicating symptoms of ischemia, but only during longer periods of ischemia.



rCBF correlates best with glutamate, followed by glycerol, whereas the L/P ratio is sensitive only after longer periods of ischemia. Clinically relevant regional metabolic derangements occur already above an rCBF of 20 mL x 100 g(-1).min(-1). Future research should focus on identifying alternative causes of metabolic derangement in subarachnoid hemorrhage patients and optimal treatment management in these patients.
Inefficacy of fresh frozen plasma in the treatment of L-asparaginase-induced coagulation factor deficiencies during ALL induction therapy.

A prospective longitudinal study was conducted to determine whether single-donor fresh frozen plasma (FFP) substitution was able to influence L-asparaginase-associated hypoproteinemia. Within a 36-month period, 20 of 42 children with ALL received a total of 42 prophylactic FFP doses at a median of 10 (5-20) mliter/kg when fibrinogen levels decreased to < 60 mg/dL and thrombin time was lengthened. Laboratory monitoring before, during and after FFP substitution showed no short-term improvements and demonstrated only a minimal increase in fibrinogen and alpha 2-antiplasmin. Plasma levels of antithrombin and plasminogen remained unchanged. Furthermore, administration of FFP had no influence on thrombin generation, the plasmin/alpha 2-antiplasmin complex or enhanced D-dimer formation.
Risk Factors for Rapid Glaucoma Disease Progression.

To determine the intraocular and systemic risk factor differences between a cohort of rapid glaucoma disease progressors and nonrapid disease progressors.



Retrospective case-control study.



Setting: Five private ophthalmology clinics.



Forty-eight rapidly progressing eyes (progression ≥1 dB mean deviation [MD]/year) and 486 non-rapidly progressing eyes (progression <1 dB MD/year). Patients were eligible if they had a diagnosis of glaucoma from their ophthalmologist and if they had greater than or equal to 5 Humphrey visual fields (24-2) conducted. Patients were excluded if their sequential visual fields showed an improvement in MD or if they had greater than 5 dB MD variation in between visits. Patients with obvious neurologic fields were excluded.


OBSERVATION PROCEDURE
Clinical and demographic data (age, sex, central corneal thickness [CCT], intraocular pressure [IOP], refraction, medications), as well as medical, surgical, and ocular histories, were collected.



Risk factor differences between the cohorts were measured using the independent t test, Wald χ2, and binomial regression analysis.



Rapid progressors were older, had significantly lower CCT and baseline IOPs, and were more likely to have pseudoexfoliation, disc haemorrhages, ocular medication changes, and IOP-lowering surgery. They also had significantly higher rates of cardiovascular disease and hypotension. Subjects with cardiovascular disease were 2.33 times more likely to develop rapidly progressive glaucoma disease despite significantly lower mean and baseline IOPs.



Cardiovascular disease is an important risk factor for rapid glaucoma disease progression irrespective of IOP control.
Influence of estrogen plus progestin on breast cancer and mammography in healthy postmenopausal women: the Women's Health Initiative Randomized Trial.

The Women's Health Initiative trial of combined estrogen plus progestin was stopped early when overall health risks, including invasive breast cancer, exceeded benefits. Outstanding issues not previously addressed include characteristics of breast cancers observed among women using hormones and whether diagnosis may be influenced by hormone effects on mammography.



To determine the relationship among estrogen plus progestin use, breast cancer characteristics, and mammography recommendations.



Following a comprehensive breast cancer risk assessment, 16 608 postmenopausal women aged 50 to 79 years with an intact uterus were randomly assigned to receive combined conjugated equine estrogens (0.625 mg/d) plus medroxyprogesterone acetate (2.5 mg/d) or placebo from 1993 to 1998 at 40 clinical centers. Screening mammography and clinical breast examinations were performed at baseline and yearly thereafter.



Breast cancer number and characteristics, and frequency of abnormal mammograms by estrogen plus progestin exposure.



In intent-to-treat analyses, estrogen plus progestin increased total (245 vs 185 cases; hazard ratio [HR], 1.24; weighted P<.001) and invasive (199 vs 150 cases; HR, 1.24; weighted P =.003) breast cancers compared with placebo. The invasive breast cancers diagnosed in the estrogen plus progestin group were similar in histology and grade but were larger (mean [SD], 1.7 cm [1.1] vs 1.5 cm [0.9], respectively; P =.04) and were at more advanced stage (regional/metastatic 25.4% vs 16.0%, respectively; P =.04) compared with those diagnosed in the placebo group. After 1 year, the percentage of women with abnormal mammograms was substantially greater in the estrogen plus progestin group (716 [9.4%] of 7656) compared with placebo group (398 [5.4%] of 7310; P<.001), a pattern which continued for the study duration.



Relatively short-term combined estrogen plus progestin use increases incident breast cancers, which are diagnosed at a more advanced stage compared with placebo use, and also substantially increases the percentage of women with abnormal mammograms. These results suggest estrogen plus progestin may stimulate breast cancer growth and hinder breast cancer diagnosis.
Thrombopoietin therapy increases platelet yields in healthy platelet donors.

The recombinant thrombopoietins have been shown to be effective stimulators of platelet production in cancer patients. It was therefore of interest to determine if one of these, pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF), could be used to increase platelet counts and consequently platelet yields from apheresis in healthy platelet donors. In a blinded, 2-cycle, crossover study, 59 platelet donors were randomized to receive a single subcutaneous injection of PEG-rHuMGDF (1 microg/kg or 3 microg/kg) or placebo and 15 days later undergo platelet apheresis. Donors treated with placebo had a median peak platelet count after PEG-rHuMGDF injection of 248 x 10(9)/L compared with 366 x 10(9)/L in donors treated with 1 microg/kg PEG-rHuMGDF and 602 x 10(9)/L in donors treated with 3 microg/kg PEG-rHuMGDF. The median maximum percentage that platelet counts increased from baseline was 10% in donors who received placebo compared with 70% in donors who received 1 microg/kg and 167% in donors who received 3 microg/kg PEG-rHuMGDF. There was a direct relationship between the platelet yield and the preapheresis platelet count: Placebo-treated donors provided 3.8 x 10(11) (range 1.3 x 10(11)-7.9 x 10(11)) platelets compared with 5.6 x 10(11) (range 2.6 x 10(11)-12.5 x 10(11)) or 11.0 x 10(11) (range 7.1 x 10(11)-18.3 x 10(11)) in donors treated with 1 microg/kg or 3 microg/kg PEG-rHuMGDF, respectively. Substandard collections (<3 x 10(11) platelets) were obtained from 26%, 4%, and 0% of the placebo, 1 microg/kg, and 3 microg/kg donors, respectively. No serious adverse events were reported; nor were there events that met the criteria for dose-limiting toxicity. Thrombopoietin therapy can increase platelet counts in healthy donors to provide a median 3-fold more apheresis platelets compared with untreated donors.
Validating prediction scales of type 2 diabetes mellitus in Spain: the SPREDIA-2 population-based prospective cohort study protocol

The incidence of type 2 diabetes mellitus (T2DM) is increasing worldwide. When diagnosed, many patients already have organ damage or advance subclinical atherosclerosis. An early diagnosis could allow the implementation of lifestyle changes and treatment options aimed at delaying the progression of the disease and to avoid cardiovascular complications. Different scores for identifying undiagnosed diabetes have been reported, however, their performance in populations of southern Europe has not been sufficiently evaluated. The main objectives of our study are: to evaluate the screening performance and cut-off points of the main scores that identify the risk of undiagnosed T2DM and prediabetes in a Spanish population, and to develop and validate our own predictive models of undiagnosed T2DM (screening model), and future T2DM (prediction risk model) after 5-year follow-up. As a secondary objective, we will evaluate the atherosclerotic burden of the population with undiagnosed T2DM.



Population-based prospective cohort study with baseline screening, to evaluate the performance of the FINDRISC, DANISH, DESIR, ARIC and QDScore, against the gold standard tests: Fasting plasma glucose, oral glucose tolerance and/or HbA1c. The sample size will include 1352 participants between the ages of 45 and 74 years.



sensitivity, specificity, positive predictive value, negative predictive value, likelihood ratio positive, likelihood ratio negative and receiver operating characteristic curves and area under curve. Binary logistic regression for the first 700 individuals (derivation) and last 652 (validation) will be performed. All analyses will be calculated with their 95% CI; statistical significance will be p<0.05.


ETHICS AND DISSEMINATION
The study protocol has been approved by the Research Ethics Committee of the Carlos III Hospital (Madrid). The score performance and predictive model will be presented in medical conferences, workshops, seminars and round table discussions. Furthermore, the predictive model will be published in a peer-reviewed medical journal to further increase the exposure of the scores.
The effect of two different renal denervation strategies on blood pressure in resistant hypertension: Comparison of full-length versus proximal renal artery ablation.

Renal denervation (RDN) is used to manage blood pressure (BP) in patients with resistant hypertension (rHT), but effectiveness is still a concern, and key arterial portion for successful RDN is not clear.



The aim of this study was to investigate the efficacy and safety of proximal versus full-length renal artery ablation in patients with resistant hypertension (rHT).



Forty-seven patients with rHT were randomly assigned to receive full-length ablation (n = 23) or proximal ablation (n = 24) of the renal arteries. All lesions were treated with radiofrequency energy via a saline-irrigated catheter. Office BP was measured during 12 months of follow-up and ambulatory BP at baseline and 6 months (n = 15 in each group).



Compared with full-length ablation, proximal ablation reduced the number of ablation points in both the right (6.1 ± 0.7 vs. 3.3 ± 0.6, P < 0.001) and the left renal arteries (6.2 ± 0.7 vs. 3.3 ± 0.8, P < 0.001), with significantly shorter RF delivery time (P < 0.001), but higher RF power (P = 0.011). Baseline office BPs was 179.4 ± 13.7/102.8 ± 9.4 mm Hg in the full-length group and 181.9 ± 12.8/103.5 ± 8.9 mm Hg in the proximal group (P > 0.5). Similar office BPs was reduced by -39.4 ± 11.5/-20.9 ± 7.1 mm Hg at 6 months and -38.2 ± 10.3/-21.5 ± 5.8 mm Hg at 12 months in the full-length group (P < 0.001), -42.0 ± 11.6/-21.4 ± 7.9 mm Hg at 6 months and -40.9 ± 10.3/-22.1 ± 5.6 mm Hg at 12 months in the proximal group (P < 0.001), and progressive BP reductions were observed over the 6 months (P < 0.001) in both groups. The drop in ambulatory 24-hr SBP and DBP were significantly less than the drop in office BP (P < 0.001). No renovascular or other adverse complications were observed.



The results indicate that proximal RDN has a similar efficacy and safety profile compared with full-length RDN, and propose the proximal artery as the key portion for RDN.
Patient-related quality assurance with different combinations of treatment planning systems, techniques, and machines

This project compares the different patient-related quality assurance systems for intensity-modulated radiation therapy (IMRT) and volumetric-modulated arc therapy (VMAT) techniques currently used in the central Germany area with an independent measuring system. The participating institutions generated 21 treatment plans with different combinations of treatment planning systems (TPS) and linear accelerators (LINAC) for the QUASIMODO (Quality ASsurance of Intensity MODulated radiation Oncology) patient model. The plans were exposed to the ArcCHECK measuring system (Sun Nuclear Corporation, Melbourne, FL, USA). The dose distributions were analyzed using the corresponding software and a point dose measured at the isocenter with an ionization chamber. According to the generally used criteria of a 10 % threshold, 3 % difference, and 3 mm distance, the majority of plans investigated showed a gamma index exceeding 95 %. Only one plan did not fulfill the criteria and three of the plans did not comply with the commonly accepted tolerance level of ±3 % in point dose measurement. Using only one of the two examined methods for patient-related quality assurance is not sufficiently significant in all cases. Im Rahmen des Projekts sollten die verschiedenen derzeit im mitteldeutschen Raum eingesetzten patientenbezogenen Qualitätssicherungssysteme zur intensitätsmodulierten Radiotherapie (IMRT) und volumenmodulierten Arc-Radiotherapie (VMAT) mit einem unabhängigen Messsystem verglichen werden. Die teilnehmenden Einrichtungen berechneten insgesamt 21 Bestrahlungspläne mit verschiedenen Planungssystemen (TPS) und Linearbeschleunigern (LINAC) für das Patientenmodell QUASIMODO (Quality ASsurance of Intensity MODulated radiation Oncology), die dann auf das ArcCHECK-Phantom (Sun Nuclear Corporation, Melbourne, FL, USA) übertragen und abgestrahlt wurden. Zur Auswertung wurde sowohl eine Punktmessung im Isozentrum als auch die Dosisverteilung in der Diodenebene des Messphantoms betrachtet. Nach den allgemein üblichen Kriterien von 10 %-Schwellenwert, 3 %-Abweichung und 3‑mm-Abstand zeigten die meisten Pläne dieser Studie einen Gamma-Index größer 95 %, lediglich ein Plan erfüllte diese Kriterien nicht. Bei der Dosispunktmessung lagen drei Pläne außerhalb der üblichen Toleranz der 3 %-Abweichung. Für die patientenbezogene Qualitätssicherung ist die Punktmessung der Dosis oder die alleinige Gammaanalyse zur Planverifizierung nicht in allen Fällen ausreichend signifikant.
Intensive dose-dense compared with conventionally scheduled preoperative chemotherapy for high-risk primary breast cancer.

To compare preoperative intense dose-dense (IDD) chemotherapy with conventionally scheduled preoperative chemotherapy in high-risk primary breast cancer (BC).



In this randomized phase III trial a total of 668 eligible primary BC patients stratified for tumors > or = 3 cm (n = 567) or inflammatory BC (n = 101) were randomly assigned to receive concurrent preoperative epirubicin/paclitaxel every 3 weeks or dose-dense and dose-escalated sequential epirubicin followed by paclitaxel every 2 weeks. All patients received three cycles of cyclophosphamide, methotrexate, and fluorouracil chemotherapy after surgery.



IDD treatment significantly improved pathologic complete response rate (18% v 10%; odds ratio [OR] 1.89; P = .008), disease-free survival (DFS; hazard ratio [HR], 0.71; P = .011), and overall survival (OS; HR, 0.83; P = .041) compared to epirubicin/paclitaxel. Patients with inflammatory BC had a particularly poor prognosis and did not appear to benefit from IDD therapy in this trial (DFS HR, 1.10; P = .739; OS HR, 1.25; P = .544). In contrast, patients with noninflammatory BC significantly benefited from IDD treatment (DFS HR, 0.65, P = .005; OS HR, 0.77, P = .013). Treatment effects in multivariate analysis were significant for noninflammatory BC (DFS HR, 0.65, P = .015; OS HR, 0.79, P = .034), but not for all patients (DFS HR, 0.76; P = .088; OS HR, 0.82; P = .059). IDD therapy was associated with significantly more nonhematologic toxicities, anemia, and thrombocytopenia, but with similar neutropenia and infection rates.



Our results support the efficacy and short-term safety of IDD as preoperative chemotherapy. IDD was less well tolerated compared to standard treatment, but improved clinical outcomes in patients with noninflammatory high-risk primary BC.
A phase IIa randomised clinical study of GNbAC1, a humanised monoclonal antibody against the envelope protein of multiple sclerosis-associated endogenous retrovirus in multiple sclerosis patients.

GNbAC1 is an immunoglobulin (IgG4) humanised monoclonal antibody against multiple sclerosis-associated retrovirus (MSRV)-Env, a protein of endogenous retroviral origin, expressed in multiple sclerosis (MS) lesions, which is pro-inflammatory and inhibits oligodendrocyte precursor cell differentiation.



This is a randomised, double-blind placebo-controlled dose-escalation study followed by a six-month open-label phase to test GNbAC1 in MS patients. The primary objective was to assess GNbAC1 safety in MS patients, and the other objectives were pharmacokinetic and pharmacodynamic assessments.



Ten MS patients were randomised into two cohorts to receive a single intravenous infusion of GNbAC1/placebo at doses of 2 or 6 mg/kg. Then all patients received five infusions of GNbAC1 at 2 or 6 mg/kg at four-week intervals in an open-label setting. Safety, brain magnetic resonance imaging (MRI), pharmacokinetics, immunogenicity, cytokines and MSRV RNA expression were studied.



All patients completed the study. GNbAC1 was well tolerated in all patients. GNbAC1 pharmacokinetics is dose-linear with mean elimination half-life of 27-37 d. Anti-GNbAC1 antibodies were not detected. Cytokine analysis did not indicate an adverse effect. MSRV-transcripts showed a decline after the start of treatment. Nine patients had stable brain lesions at MRI.



The safety, pharmacokinetic profile, and pharmacodynamic responses to GNbAC1 are favourable in MS patients over a six-month treatment period.
Contribution of chemotherapy mobilization to disease control in multiple myeloma treated with autologous hematopoietic cell transplantation

In patients with multiple myeloma (MM) undergoing autologous hematopoietic cell transplantation (auto-HCT), peripheral blood progenitor cells may be collected following mobilization with growth factor alone (GF) or cytotoxic chemotherapy plus GF (CC+GF). It is uncertain whether the method of mobilization affects post-transplant outcomes. We compared these mobilization strategies in a retrospective analysis of 968 patients with MM from the Center for International Blood and Marrow Transplant Research database who received an auto-HCT in the US and Canada between 2007 and 2012. The kinetics of neutrophil engraftment (⩾0.5 × 109/L) was similar between groups (13 vs 13 days, P=0.69) while platelet engraftment (⩾20 × 109/L) was slightly faster with CC+GF (19 vs 18 days, P=0.006). Adjusted 3-year PFS was 43% (95% confidence interval (CI) 38–48) in GF and 40% (95% CI 35–45) in CC+GF, P=0.33. Adjusted 3-year OS was 82% (95% CI 78–86) vs 80% (95% CI 75–84), P=0.43 and adjusted 5-year OS was 62% (95% CI 54–68) vs 60% (95% CI 52–67), P=0.76, for GF and CC+GF, respectively. We conclude that MM patients undergoing auto-HCT have similar outcomes irrespective of the method of mobilization and found no evidence that the addition of chemotherapy to mobilization contributes to disease control.