nils-herrmann/clean_scirepeval huggingface dataset:
Clinical outcomes of late rather than early full-donor chimerism in patients with advanced lymphomas receiving nonmyeloablative allogeneic hematopoietic SCT

Allogeneic hematopoietic SCT (HSCT) can ideally provide long-term remission in advanced lymphoma patients by capturing a graft-vs-tumor (GVT) effect. On the basis of a murine model, we attempted to optimize a GVT effect through nonmyeloablative therapy and HLA-matched related donor HSCT with intentional induction of mixed chimerism followed by prophylactic donor lymphocyte infusion. A total of 26 advanced lymphoma patients were separated into an early and late full-donor chimerism (FDC) group using a median of 45 days post-HSCT as the defining point for FDC. Upon generating these groups, analysis by Student's t-test demonstrated that they were statistically distinct in time to develop FDC (P<0.01). There was a trend toward improved CR rates in the late group relative to the early group (62 vs 31%; P=0.12). A trend toward improved progression-free survival at 5 years was also observed in the late compared to the early group by Kaplan–Meier analysis (38 vs 8%; P=0.081). However, this did not correlate to a significant overall survival benefit. In conclusion, these data support the observation from our mouse models that the most potent GVT effect occurs in mixed chimeras with late chimerism conversion.
Inter-patient variability and impact of proton pump inhibitors on platelet reactivity after prasugrel.

Although there is considerable variability of platelet reactivity among patients treated with clopidogrel, little is known about inter-individual differences and possible role of proton pump inhibitors (PPIs) after prasugrel. We defined the extent of inter-patient variability, and evaluated the impact of PPI interaction in prasugrel-treated patients with acute coronary syndrome (ACS). Between January 2010 and May 2011, 104 prospective, high-risk patients with ACS were recruited into this multicentre, prospective, observational study. Twelve to 24 hours after receiving 60 mg loading dose of prasugrel, light transmission aggregometry (LTA) and whole blood impedance aggregometry (Multiplate) were used to assess platelet activity. Platelet function measurements were repeated during maintenance phase on reduced (5 mg) or on conventional (10 mg) doses of prasugrel. High platelet reactivity (HPR) was defined according to the consensus document of the Working Group on High On-Treatment Platelet Reactivity (LTA:>46%; Multiplate:>47U). Compared to maintenance doses, 60 mg loading dose of prasugrel provided significantly greater platelet reactivity inhibition (p<0.05). There were no significant differences between the conventional and reduced maintenance doses. Notably, a remarkable inter-patient variability was present in platelet reactivity after all doses of prasugrel, and the prevalence of HPR was significantly higher during the maintenance doses (p<0.05). Although median platelet reactivity values were consistently higher when prasugrel was used in combination with PPIs, these differences were not significant (p≥0.17). Despite potent platelet inhibition, inter-patient variability is present after all tested doses of prasugrel. The 60 mg loading dose is superior to conventional and reduced maintenance doses in terms of platelet reactivity inhibition and regarding the prevention of HPR.
Evaluation of responsive gene expression as a sensitive and specific biomarker in patients with ulcerative colitis.

Clinical trials in ulcerative colitis (UC) rely on certain parameters to evaluate responses that are highly subjective or of low sensitivity. Here, using a select group of genes, we tested the accuracy of gene expression analysis as a biomarker of clinical, endoscopic, and histologic improvements.



Intestinal biopsies were obtained from UC patients included in two cohorts. Cohort 1 was used to select for genes whose expression was modulated in active (vs. inactive) UC. Cohort 2 included patients recruited in a phase II study receiving placebo, mesalazine, or dersalazine sodium for 4 weeks. The expression of 44 genes identified in Cohort 1 was assessed at weeks 0 and 4, and was then correlated with biomarkers, as well as with clinical, endoscopic, and histologic scores.



Significant changes in the expression of 31 of the 44 genes tested were detected in Cohort 2 at week 4. Gene expression (ΔCt) significantly correlated with the total Mayo score, C-reactive protein (CRP), and fecal calprotectin. The number of genes significantly regulated at week 4 was highly associated with histologic and endoscopic responses. Logistic regression analysis identified four separate genes (IFITM1, ITGB2, IL1R2, IL2RA) whose relative change was independently associated with endoscopic remission with high specificity and sensitivity.



Change in the expression of a select set of genes can serve as an early biomarker, one with high specificity and sensitivity to clinical, endoscopic, and histologic responses. This could represent a new tool for identifying early response to treatment in mild to moderately active UC patients.
EEG utilization in Canadian intensive care units: A multicentre prospective observational study

We have previously shown that electroencephalography (EEG) may be an underutilized monitoring modality in a single general medical-surgical ICU, that does not have a specific neurocritical care consultation service or neurocritical care unit. The present study was designed to describe the pattern of EEG utilization across 3 academic ICUs in Ontario, Canada that use different models of neurocritical care.



In this prospective multicentre observational study, ICU patients were screened weekly for 6 non-consecutive weeks to determine if they met the ESICM's recommendations or suggestions for EEG monitoring. If EEGs were performed, the results were recorded. Three models of neurocritical care provision were examined in 3 academic tertiary ICUs. Site 1 is an intensivist-led, medical-surgical ICU with no specific neurocritical care consultation service. The second site is also an intensivist led medical-surgical ICU, but with a formal neurocritical care consultation service. The third site is a virtual neurological and neurotrauma ICU within a medical-surgical ICU, staffed by rotating neurointensivists and general intensivists.



Of the 375 patients who were screened, 127 patients (34%) met at least one ESICM indication for EEG monitoring. Among the 127 patients, 46 patients (37%) had an EEG performed. Site 1 had the highest proportion of EEGs performed. The most common indication for EEG monitoring was for patients with unexplained altered level of consciousness, in the absence of primary brain injury. For the EEGs performed per ESICM indication, the majority of epileptiform abnormalities were found in patients admitted with status epilepticus.



EEG may be underutilized in Canadian ICUs. The impact on patient management and outcomes are unknown.
Influence of amiodarone on urinary excretion of 6beta-hydroxycortisol in humans.

The present study was undertaken to evaluate the use of cortisol 6beta-hydroxylation in defining the effect of amiodarone on cytochrome CYP3A activity. To accomplish this goal, the in vivo activity of CYP3A was estimated by measuring the 24-hour urinary excretion of 6beta-hydroxycortisol (6beta-OHC) and by calculating 24-hour ratio of 6beta-hydroxycortisol to urinary free cortisol (6beta-OHC/UFC ratio). Nine cardiac patients scheduled for amiodarone treatment were recruited to participate in this study. Urine was collected over a 24-hour period from each subject before the first amiodarone administration and during the third day of oral administration of amiodarone (200 mg four times daily as a loading dose). Three days of amiodarone treatment caused a significant decrease (p<0.05) in both the 6beta-OHC/UFC ratio and the 24-hour urinary excretion of 6beta3-OHC. These results suggest that amiodarone is an inhibitor of CYP3A activity.
Safety and efficacy of the PrePex device for rapid scale-up of male circumcision for HIV prevention in resource-limited settings.

To assess the safety and efficacy of the PrePex device for nonsurgical circumcision in adult males as part of a comprehensive HIV prevention program in Rwanda.



Single-center 6-week noncontrolled study in which healthy men underwent circumcision using the PrePex device, which employs fitted rings to clamp the foreskin, leading to distal necrosis. In the first phase of the study, the feasibility of the procedure was tested on 5 subjects in a sterile environment; in the main phase, an additional 50 subjects were circumcised in a nonsterile setting by physicians or a nurse. Outcome measures included the rate of successful circumcision, time to complete healing, pain, and adverse events.



In the feasibility phase, all 5 subjects achieved complete circumcision without adverse events. In the main phase, all 50 subjects achieved circumcision with 1 case of diffuse edema after device removal, which resolved with minimal intervention. Pain was minimal except briefly during device removal (day 7 after placement in most cases). The entire procedure was bloodless, requiring no anesthesia, no suturing, and no sterile settings. Subjects had no sick/absent days associated with the procedure. Median time for complete healing was 21 days after device removal. There were no instances of erroneous placement and no mechanical problems with the device.



The PrePex device was safe and effective for nonsurgical adult male circumcision without anesthesia or sterile settings and may be useful in mass circumcision programs to reduce the risk of HIV infection, particularly in resource-limited settings.
Targeting the kidney in acute heart failure: can old drugs provide new benefit? Renal Optimization Strategies Evaluation in Acute Heart Failure (ROSE AHF) trial.

Acute Decompensated Heart Failure Represents an Enormous Healthcare Burden Acute decompensated heart failure (ADHF) is the most common cause of hospital admission in persons aged >65 years, accounting for 1 000 000 admissions and >6 million hospital days. The total cost of HF care in the United States is currently estimated at $21 billion and is projected to increase to $53 billion in 2030 with the majority of costs (80%) related to ADHF hospitalizations. The prognosis of patients admitted with ADHF is dismal, with a 20% to 30% readmission rate and a 20% to 30% mortality rate within 6 months after admission.
96 Week Follow-Up of HIV-Infected Patients in Rescue with Raltegravir Plus Optimized Backbone Regimens: A Multicentre Italian Experience

Long term efficacy of raltegravir (RAL)-including regimens in highly pre-treated HIV-1-infected patients has been demonstrated in registration trials. However, few studies have assessed durability in routine clinical settings.



Antiretroviral treatment-experienced patients initiating a RAL-containing salvage regimen were enrolled. Routine clinical and laboratory follow-up was performed at baseline, week 4, 12, and every 12 weeks thereafter. Data were censored at week 96.



Out of 320 patients enrolled, 292 (91.25%) subjects maintained their initial regimen for 96 weeks; 28 discontinued prematurely for various reasons: death (11), viral failure (8), adverse events (5), loss to follow-up (3), consent withdrawal (1). Eight among these 28 subjects maintained RAL but changed the accompanying drugs. The mean CD4+ T-cell increase at week 96 was 227/mm(3); 273 out of 300 patients (91%), who were still receiving RAL at week 96, achieved viral suppression (HIV-1 RNA <50 copies/mL). When analyzing the immuno-virologic outcome according to the number of drugs used in the regimen, 2 (n = 45), 3 (n = 111), 4 (n = 124), or >4 (n = 40), CD4+ T-cell gain was similar across strata: +270, +214, +216, and +240 cells/mm(3), respectively, as was the proportion of subjects with undetectable viral load. Laboratory abnormalities (elevation of liver enzymes, total cholesterol and triglycerides) were rare, ranging from 0.9 to 3.1%. The mean 96-week total cholesterol increase was 23.6 mg/dL.



In a routine clinical setting, a RAL-based regimen allowed most patients in salvage therapy to achieve optimal viral suppression for at least 96 weeks, with relevant immunologic gain and very few adverse events.
American College of Cardiology/American Heart Association/European Society of Cardiology/World Heart Federation universal definition of myocardial infarction classification system and the risk of cardiovascular death: observations from the TRITON-TIMI 38 trial (Trial to Assess Improvement in Therape

The availability of more sensitive biomarkers of myonecrosis and a new classification system from the universal definition of myocardial infarction (MI) have led to evolution of the classification of MI. The prognostic implications of MI defined in the current era have not been well described.



We investigated the association between new or recurrent MI by subtype according to the European Society of Cardiology/American College of Cardiology/American Heart Association/World Health Federation Task Force for the Redefinition of MI Classification System and the risk of cardiovascular death among 13 608 patients with acute coronary syndrome in the Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition with Prasugrel-Thrombolysis in Myocardial Infarction 38 (TRITON-TIMI 38). The adjusted risk of cardiovascular death was evaluated by landmark analysis starting at the time of the MI through 180 days after the event. Patients who experienced an MI during follow-up had a higher risk of cardiovascular death at 6 months than patients without an MI (6.5% versus 1.3%, P<0.001). This higher risk was present across all subtypes of MI, including type 4a (peri-percutaneous coronary intervention, 3.2%; P<0.001) and type 4b (stent thrombosis, 15.4%; P<0.001). After adjustment for important clinical covariates, the occurrence of any MI was associated with a 5-fold higher risk of death at 6 months (95% confidence interval 3.8-7.1), with similarly increased risk across subtypes.



MI is associated with a significantly increased risk of cardiovascular death, with a consistent relationship across all types as defined by the universal classification system. These findings underscore the clinical relevance of these events and the importance of therapies aimed at preventing MI.
Risk factors for efflux pump overexpression in fluoroquinolone-resistant Escherichia coli.

We conducted a case-control study to identify risk factors for efflux overexpression, an important mechanism of fluoroquinolone resistance, among patients with fluoroquinolone-resistant Escherichia coli (FQREC) gastrointestinal tract colonization.



Three annual fecal surveillance surveys were performed hospital-wide, and all patients colonized with FQREC (levofloxacin minimum inhibitory concentration, ≥8 μg/mL) were included in the study. Cases and controls were defined on the basis of overexpression of the AcrAB efflux pump, as measured by the organic solvent tolerance (OST) assay. A multivariable logistic regression model was developed to identify risk factors for OST positivity among patients with FQREC colonization.



Eighty-nine patients were colonized with FQREC: 44 (49.4%) and 45 (50.6%) patients had isolates that were OST-positive and OST-negative, respectively. On multivariable analyses, location on the surgical service was significantly associated with recovery of an OST-positive isolate (odds ratio, 7.36; 95% confidence interval, 1.82-29.7; P = .005). Furthermore, patients who had received a first-generation cephalosporin in the 30 days prior to sampling were less likely to have an OST-positive isolate (odds ratio, 0.20; 95% confidence interval, .04-.94; P = .04).



Among phenotypically identical FQREC isolates, different factors may drive the emergence of different resistance mechanisms. Further studies are needed to elucidate the relationship between antimicrobial use and specific resistance mechanisms.
Oxidative stress-associated hypertension in surgically induced brain injury patients: effects of β-blocker and angiotensin-converting enzyme inhibitor.

Postoperative hypertension is a common problem in patients undergoing surgical procedures, and the modification of this response could result in improved surgical outcome. Although it is recognized that the incidence of postoperative hypertension is higher in neurosurgical procedures, mechanisms behind this are not well understood. Oxidative stress is an important component of brain injury, and free radicals can influence blood pressure by a number of mechanisms. This study examined the effect of pretreatment with antihypertensive agents on postoperative hypertension in patients undergoing neurosurgery for supratentorial brain tumors and the role of oxidative stress in the process.



Forty-nine consecutive patients who underwent surgery for supratentorial brain tumors were divided in to three groups (control, Tab. Glucose; atenolol; and lisinopril groups). Blood was drawn at three time points (1 d before the surgery, at the time of dura opening, and at the time of extubation). Hemodynamic parameters in all three groups and levels of malondialdehyde, protein carbonyl content, nitrate, and α-tocopherol in serum at various time points were analyzed.



The results showed that perioperative hemodynamic changes were highly associated with oxidative stress parameters in all the three groups. It was seen that atenolol and lisinopril significantly decreased levels of malondialdehyde, protein carbonyl content, and nitrate in the intraoperative period (P < 0.05), an effect which continued postoperatively.



The results demonstrate that pretreatment with β-receptor blocker (atenolol) or angiotensin-converting enzyme inhibitor (lisinopril) reduces postoperative hypertension in patients undergoing neurosurgery, and inhibition of oxidative stress may be a potential mechanism for this effect.
The Impact of the Good Behavior Game, a Universal Classroom-Based Preventive Intervention in First and Second Grades, on High-Risk Sexual Behaviors and Drug Abuse and Dependence Disorders into Young Adulthood

The Good Behavior Game (GBG), a method of teacher classroom behavior management, was tested in first- and second-grade classrooms in 19 Baltimore City Public Schools beginning in the 1985–1986 school year. The intervention was directed at the classroom as a whole to socialize children to the student role and reduce aggressive, disruptive behaviors, confirmed antecedents of a profile of externalizing problem outcomes. This article reports on the GBG impact on the courses and interrelationships among aggressive, disruptive behavior through middle school, risky sexual behaviors, and drug abuse and dependence disorders through ages 19–21. In five poor to lower-middle class, mainly African American urban areas, classrooms within matched schools were assigned randomly to either the GBG intervention or the control condition. Balanced assignment of children to classrooms was made, and teachers were randomly assigned to intervention or control. Analyses involved multilevel growth mixture modeling. By young adulthood, significant GBG impact was found in terms of reduced high-risk sexual behaviors and drug abuse and dependence disorders among males who in first grade and through middle school were more aggressive, disruptive. A replication with the next cohort of first-grade children with the same teachers occurred during the following school year, but with minimal teacher mentoring and monitoring. Findings were not significant but generally in the predicted direction. A universal classroom-based prevention intervention in first- and second-grade classrooms can reduce drug abuse and dependence disorders and risky sexual behaviors.
Prostate cancer-derived urine exosomes: a novel approach to biomarkers for prostate cancer

Herein, we describe a novel approach in the search for prostate cancer biomarkers, which relies on the transcriptome within tumour exosomes. As a proof-of-concept, we show the presence of two known prostate cancer biomarkers, PCA-3 and TMPRSS2:ERG the in exosomes isolated from urine of patients, showing the potential for diagnosis and monitoring cancer patients status.
Paracetamol in osteoarthritis of the knee.

Paracetamol is a recommended symptomatic treatment of osteoarthritis (OA), but in clinical trials sample sizes have been relatively small and variable daily doses of paracetamol have been used.



To determine the therapeutic efficacy of paracetamol in OA of the knee and identify predictive factors of clinical response to treatment.



A double blind, parallel group, placebo controlled trial of analgesic efficacy and safety of paracetamol versus placebo including 779 patients with OA of the knee. Patients were randomly assigned to receive paracetamol 4 g/day (n = 405) or placebo (n = 374) for 6 weeks. Symptomatic OA of the knee was required at inclusion with global pain intensity of the knee during physical activities for the past 24 hours of >or=30 mm on a 100 mm visual analogue scale. The primary end point was a 30% decrease of global pain intensity of the knee. Intention to treat analyses were performed.



The percentage of responders did not differ significantly between groups: 52.6% and 51.9% in paracetamol and placebo groups, respectively (p = 0.840). In a subgroup of patients with chronic mechanical knee pain without signs of inflammation (n = 123), the mean change in pain intensity from baseline was 25.2 mm v 15.2 mm, in the paracetamol (n = 63) and placebo (n = 60) groups, respectively-mean difference 10.0 mm; 95% CI 1.0 to 19.0; p = 0.0294. No serious adverse events were attributable to treatment.



A statistically significant symptomatic effect of oral paracetamol 4 g/day over placebo was not found, suggesting that paracetamol use in symptomatic OA of the knee should be further explored. The tolerability and safety of paracetamol, at the recommended maximum dose of 4 g/day, was confirmed over 6 weeks.
Factors associated with discussion of sexual activity and contraception in women with HIV.

Contraceptive use is important for reproductive-aged women living with HIV to plan and optimise safety of pregnancies. Clinicians play a vital role in counselling patients about contraception and safe sexual activity. This study aimed to determine the frequency and predictors of discussions regarding sexual activity and contraceptive use.



Retrospective clinical study of all reproductive-aged women (n=128) treated for HIV between 2010 and 2012 at two metropolitan hospitals. Evidence of discussion between treating doctors and patients regarding sexual activity and contraception and variables including patient age, gender of doctor, time since HIV diagnosis, previous pregnancy, country of birth and antiretroviral regimen were obtained from medical records.



Sexual activity status was documented for 54% of the women and discussion regarding contraception was recorded for less than one-third of the study participants. Contraceptive use was not recorded in 63% of the medical records. In the study cohort 27% of the women used contraception, 10% did not use contraception, and when a discussion regarding sexual activity was documented, contraception was 3.7 times more likely to also be discussed (p=0.04). Excluding women who were pregnant, women who were documented as using contraception were 1.8 times as likely to have had a discussion about contraception documented (p=0.05). After adjustment for other factors, previous pregnancy, gender of doctor and age of patient were not associated with discussions regarding sexual activity or contraception.



Discussions regarding sexual activity and contraception between HIV-infected women of reproductive age and their clinicians were inconsistent and suboptimal. Mechanisms to facilitate regular discussion about sexual activity and contraception between clinicians and women with HIV warrant further investigation.