nils-herrmann/clean_scirepeval huggingface dataset:
Safety of telbivudine treatment for chronic hepatitis B for the entire pregnancy.

Orally administered nucleus(t)ide analogues (NA) have brought about a simple, safe and effective therapeutic approach for chronic hepatitis B (CHB). However, treatment duration is long and some female patients become pregnant during treatment. In recent years, there have been gradually increasing reports on the safety of telbivudine (LdT) treatment for chronic hepatitis B virus (HBV) infection in the third trimester of pregnancy to block mother-to-infant transmission (MTIT) of HBV; however, the safety of LdT treatment for chronic HBV infection for the entire pregnancy has not been reported. The aim of the present study was to evaluate the safety of LdT treatment for chronic HBV infection for the entire pregnancy and provide a reference for HBV-infected fertile women on how to block MTIT of HBV. Eighty-six pregnant women who received LdT treatment either before or in early pregnancy were enrolled in the study. Adverse events were prospectively observed for the entire pregnancy and perinatal period, and short-term and long-term follow-up of infants was conducted, monitoring the abnormalities of infants and blocking rate of MTIT with LdT treatment. Eighty-six pregnant women treated with LdT had a total of 89 pregnancies: 6 (6.7%) had early embryonic death or spontaneous abortion, 1 (1.1%) had ectopic pregnancy and three had a second pregnancy after initial abortion. Fifty-one mothers completed pregnancy: one had induction of labour at 24 weeks of pregnancy for cleft lip and palate of the foetus and 50 delivered 52 full-term live infants. One infant had right ear accessories, and the total occurrence of congenital abnormality was 3.8%. Thirty-nine infants were followed up for more than 6 months and completed all examinations for MTIT. None of the infants were HBsAg positive, resulting in a 100% success rate of blocking MTIT. All mothers maintained good liver function during the third trimester of pregnancy; 86% maintained complete virological response (HBV DNA <500 copies/mL) prior to delivery, and none developed progression of liver disease. Factors leading to increased adverse effects and drug resistance were not found. LdT treatment is safe and effective in chronic HBV-infected pregnant mothers for the entire pregnancy.
Frequency and pattern of de-novo three-vessel and left main coronary artery disease; insights from single center enrolment in the SYNTAX study.

To characterize the current patient population regarding extent and pattern of coronary artery disease (CAD) in a routine cardiac catheterization practice with special focus on de-novo three-vessel coronary artery and/or left main disease (3-VD/LM) during enrolment in the SYNTAX study (synergy between PCI with Taxus drug-eluting stent and cardiac surgery) comparing percutaneous coronary intervention (PCI) with drug-eluting stents (DES) and coronary artery bypass grafting (CABG) in 3-VD/LM.



During a 4-month study enrolment period, a total of 3319 consecutive adult patients undergoing coronary angiography were prospectively recorded. Patients with de-novo 3-VD/LM were screened in the daily heart team conference by interventional cardiologists and cardiac surgeons concerning suitability for study enrolment. Complexity of CAD was quantified by the SYNTAX score.



A total of 694 patients (20.9%) presented with 3-VD/LM, of which 271 had previous CABG and 232 previous PCI treatment. Of the 191 patients with de-novo 3-VD/LM, SYNTAX study exclusion criteria were present in 87 patients consisting mostly of acute myocardial infarction (n=47) or concomitant indications for additional heart surgery (n=35). A total of 104 patients (54.4% of all screened) were potentially suitable for study enrolment. Of these, 13 patients refused study participation, 10 presented with uncertain protocol adherence and 6 were already participating in other cardiovascular trials. A total of 67 patients were therefore enrolled in the SYNTAX study, representing 9.7% of 3-VD/LM and 35.1% of all screened patients. Twenty-four patients were not amenable for PCI and were therefore assigned to the CABG registry. Compared to the randomized cohort, these patients had more complex CAD (SYNTAX score 34 vs 26, p=0.003) with significantly more chronic coronary vessel occlusion (70.8% vs 22.5%, p=0.04). In the randomized cohort, CABG and PCI patients were comparable in age (PCI 69.7 years vs CABG 67.2 years), additive EuroSCORE (4.8 vs 4.4), EF (57.8% vs 52.4%), number of coronary lesions (4.5 vs 4.6), left main disease (42.9% vs 52.6%) and coronary vessel occlusion.



Patients with de-novo 3-VD/LM represented a small proportion of patients undergoing coronary angiography at our center. However, SYNTAX study inclusion and randomization rates of these screened patients were high. Chronic vessel occlusion and high SYNTAX scores were more common in CABG registry patients compared to randomized patients.
Carcinoid heart disease: impact of pulmonary valve replacement in right ventricular function and remodeling.

Carcinoid heart disease characteristically affects tricuspid (TV) and pulmonary valves (PV), and TV replacement is helpful in selected patients. There is uncertainty, however, regarding optimal surgical management of PV regurgitation.



We reviewed 22 patients having operation for carcinoid heart disease and compared those having TV and PV replacement (n=12), to those who underwent TV replacement and excision of the PV (n=10). Pre- and postoperative right ventricular (RV) size and dysfunction were assessed by consensus of 2 echocardiographers blinded to type of surgical treatment. RV dysfunction was graded as none (0), mild (1), moderate (2), or severe (3). RV size was graded as normal (0), or mild (1), moderate (2), or severe (3) enlargement. Preoperatively, RV size (2.2+/-0.8 [no PVR]versus 2.7+/-0.6 [with PVR], P=0.15), RV dysfunction (0.9+/-0.9 [no PVR]versus 1.4+/-0.7 [with PVR], P=0.14), and NYHA class were similar in the 2 groups. Postop RV size decreased inpatients with PVR, 2.7+/-0.6 to 1.7+/-1.0 (P=0.008), but did not change appreciably in those without PVR, 2.2+/-0.8 to 2.3+/-0.8 (P=0.67). There was no significant change in RV dysfunction after surgery, 1.4+/-0.7 to 1.8+/-0.9 with PVR (P=0.26) and 0.9+/-0.9 to 1.6+/-0.9 without PVR (P=0.07).



PV replacement appears to have a beneficial effect on RV size in patients after surgery for carcinoid heart disease. This may have important implications for RV remodeling after PV replacement.
Vascular effects, efficacy and safety of nintedanib in patients with advanced, refractory colorectal cancer: a prospective phase I subanalysis

Nintedanib is a potent, oral angiokinase inhibitor that targets VEGF, PDGF and FGF signalling, as well as RET and Flt3. The maximum tolerated dose of nintedanib was evaluated in a phase I study of treatment-refractory patients with advanced solid tumours. In this preplanned subanalysis, the effect of nintedanib on the tumour vasculature, along with efficacy and safety, was assessed in 30 patients with colorectal cancer (CRC). Patients with advanced CRC who had failed conventional treatment, or for whom no therapy of proven efficacy existed, were treated with nintedanib ranging from 50–450 mg once-daily (n = 14) or 150–250 mg twice-daily (n = 16) for 28 days. After a 1-week rest, further courses were permitted in the absence of progression or undue toxicity. The primary objective was the effect on the tumour vasculature using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and expressed as the initial area under the DCE-MRI contrast agent concentration–time curve after 60 seconds (iAUC60) or the volume transfer constant between blood plasma and extravascular extracellular space (Ktrans). Patients received a median of 4.0 courses (range: 1–13). Among 21 evaluable patients, 14 (67%) had a ≥40% reduction from baseline in Ktrans and 13 (62%) had a ≥40% decrease from baseline in iAUC60, representing clinically relevant effects on tumour blood flow and permeability, respectively. A ≥40% reduction from baseline in Ktrans was positively associated with non-progressive tumour status (Fisher’s exact: p = 0.0032). One patient achieved a partial response at 250 mg twice-daily and 24 (80%) achieved stable disease lasting ≥8 weeks. Time to tumour progression (TTP) at 4 months was 26% and median TTP was 72.5 days (95% confidence interval: 65–114). Common drug-related adverse events (AEs) included nausea (67%), vomiting (53%) and diarrhoea (40%); three patients experienced drug-related AEs ≥ grade 3. Four patients treated with nintedanib once-daily had an alanine aminotransferase and/or aspartate aminotransferase increase ≥ grade 3. No increases > grade 2 were seen in the twice-daily group. Nintedanib modulates tumour blood flow and permeability in patients with advanced, refractory CRC, while achieving antitumour activity and maintaining an acceptable safety profile.
Genomic Profiling Reveals the Potential Role of TCL1A and MDR1 Deficiency in Chemotherapy-Induced Cardiotoxicity

Anthracyclines, such as doxorubicin (Adriamycin), are highly effective chemotherapeutic agents, but are well known to cause myocardial dysfunction and life-threatening congestive heart failure (CHF) in some patients.



To generate new hypotheses about its etiology, genome-wide transcript analysis was performed on whole blood RNA from women that received doxorubicin-based chemotherapy and either did, or did not develop CHF, as defined by ejection fractions (EF)≤40%. Women with non-ischemic cardiomyopathy unrelated to chemotherapy were compared to breast cancer patients prior to chemo with normal EF to identify heart failure-related transcripts in women not receiving chemotherapy. Byproducts of oxidative stress in plasma were measured in a subset of patients.



The results indicate that patients treated with doxorubicin showed sustained elevations in oxidative byproducts in plasma. At the RNA level, women who exhibited low EFs after chemotherapy had 260 transcripts that differed >2-fold (p<0.05) compared to women who received chemo but maintained normal EFs. Most of these transcripts (201) were not altered in non-chemotherapy patients with low EFs. Pathway analysis of the differentially expressed genes indicated enrichment in apoptosis-related transcripts. Notably, women with chemo-induced low EFs had a 4.8-fold decrease in T-cell leukemia/lymphoma 1A (TCL1A) transcripts. TCL1A is expressed in both cardiac and skeletal muscle, and is a known co-activator for AKT, one of the major pro-survival factors for cardiomyocytes. Further, women who developed low EFs had a 2-fold lower level of ABCB1 transcript, encoding the multidrug resistance protein 1 (MDR1), which is an efflux pump for doxorubicin, potentially leading to higher cardiac levels of drug. In vitro studies confirmed that inhibition of MDR1 by verapamil in rat H9C2 cardiomyocytes increased their susceptibility to doxorubicin-induced toxicity.



It is proposed that chemo-induced cardiomyopathy may be due to a reduction in TCL1A levels, thereby causing increased apoptotic sensitivity, and leading to reduced cardiac MDR1 levels, causing higher cardiac levels of doxorubicin and intracellular free radicals. If so, screening for TCL1A and MDR1 SNPs or expression level in blood, might identify women at greatest risk of chemo-induced heart failure.
Community acquired versus hospital acquired hyponatremia in acute heart failure: Association with clinical characteristics and outcomes.

Hyponatremia is the commonest electrolyte abnormality in patients hospitalized with heart failure (HF)  with a prevalence of 19%–25% [2–4]. It is a result of either increased neurohormonal activation that reflects the severity of HF  or due to effect of diuretics. Admission hyponatremia in acute HF is a poor prognostic indicator associated with prolonged hospital stay, higher rates of rehospitalization [6–8], and higher short and long term mortality [2,4,9]. There is scant data that compares community acquired hyponatremia (CAH) and hospital acquired hyponatremia (HAH) in HF. Shchekochikhin and colleagues showed that HAH is also associatedwith increased in-hospitalmortality and length of stay similar to what have been described with CAH [10]. However, no study examined intermediate-term post-discharge outcomes. We hypothesized that HAH has favorable post-discharge outcome compared with CAH in HF. In this analysis we compared the characteristics and intermediate-term outcomes of patients with acute systolic HF with either CAH or HAH. The study is an analysis from the Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness (ESCAPE) trial. Briefly, the ESCAPE trial is a National Heart, Lung and Blood Institute (NHLBI)-sponsored multicenter study that randomized 433 patients with acute systolic HF to clinical assessment alone versus clinical assessment guided by pulmonary artery catheterization (PAC). The study showed that the PAC did not improve or worsen HF outcomes. Design, rationale, and results of the ESCAPE trial have been previously published [11,12]. Sodium level was measured at multiple time points including hospital admission and discharge. We defined CAH as a serum sodium
Exercise training intervention after coronary angioplasty: the ETICA trial.

The goal of this study was to determine the effects of exercise training (ET) on functional capacity and quality of life (QOL) in patients who received percutaneous transluminal coronary angioplasty (PTCA) or coronary stenting (CS), the effects on the restenosis rate and the outcome.



It is unknown whether ET induces beneficial effects after coronary angioplasty.



We studied 118 consecutive patients with coronary artery disease (mean age 57+/-10 years) who underwent PTCA or CS on one (69%) or two (31%) native epicardial coronary arteries. Patients were randomized into two matched groups. Group T (n = 59) was exercised three times a week for six months at 60% of peak VO2. Group C (n = 59) was the control group.



Only trained patients had significant improvements in peak VO2 (26%, p < 0.001) and quality of life (26.8%, p = 0.001 vs. C). The angiographic restenosis rate was unaffected by ET (T: 29%; C: 33%, P = NS) and was not significantly different after PTCA or CS. However, residual diameter stenosis was lower in trained patients (-29.7%, p = 0.045). In patients with angiographic restenosis, thallium uptake improved only in group T (19%; p < 0.001). During the follow-up (33+/-7 months) trained patients had a significantly lower event rate than controls (11.9 vs. 32.2%, RR: 0.71, 95% confidence interval [CI]: 0.60 to 0.91, p = 0.008) and a lower rate of hospital readmission (18.6 vs. 46%, RR: 0.69, 95% CI: 0.55 to 0.93, p < 0.001).



Moderate ET improves functional capacity and QOL after PTCA or CS. During the follow-up, trained patients had fewer events and a lower hospital readmission rate than controls, despite an unchanged restenosis rate.
Effects of a 10-week toe-out gait modification intervention in people with medial knee osteoarthritis: a pilot, feasibility study.

To examine the feasibility of a 10-week gait modification program in people with medial tibiofemoral knee osteoarthritis (OA), and to assess changes in clinical and biomechanical outcomes.



Fifteen people with medial knee OA completed 10 weeks of gait modification focusing on increasing toe-out angle during stance 10° compared to their self-selected angle measured at baseline. In addition to adherence and performance difficulty outcomes, knee joint symptoms (Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscale and total score, numerical rating scale (NRS) of pain), and knee joint loading during gait (late stance peak knee adduction moment (KAM)) were assessed.



Participants were able to perform the toe-out gait modification program with minimal to moderate difficulty, and exhibited significant increases in self-selected toe-out angle during walking (P < 0.001). Joint discomfort was reported by five participants (33%) in the hip or knee joints, though none lasted longer than 2 weeks. Participants reported statistically significant reductions in WOMAC pain (P = 0.02), NRS pain (P < 0.001), WOMAC total score (P = 0.02), and late stance KAM (P = 0.04).



These preliminary findings suggest that toe-out gait modification is feasible in people with medial compartment knee OA. Preliminary changes in clinical and biomechanical outcomes provide the impetus for conducting larger scale studies of gait modification in people with knee OA to confirm these findings.
Does peripheral nerve degeneration affect circulatory responses to head-up tilt in spinal cord-injured individuals?

Despite the loss of centrally mediated sympathetic vasoconstriction, spinal cord-injured (SCI) individuals cope surprisingly well with orthostatic challenges. In the pathophysiology of this intriguing observation spinal sympathetic—, veno-arteriolar—(VAR), and myogenic reflexes seem to play a role. The purpose of this study was to assess whether central (stroke volume, heart rate, blood pressure and total peripheral resistance) and peripheral (leg blood flow, leg vascular resistance and femoral arterial diameter) hemodynamic responses to head-up tilt are different in two groups of SCI patients, i. e., SCI individuals with upper motor neuron lesions (who have spinal reflexes, VAR and myogenic reflexes) (U; n=6) and those with lower motor neuron lesion (who have no spinal reflexes, perhaps no VAR due to nerve degeneration, but intact myogenic reflexes) (L; n=5). Ten healthy male individuals served as controls (C) (normal supraspinal sympathetic control and presence of all reflexes). After 10 min supine rest all individuals were tilted to 30° head-up tilt. Red blood cell velocity (measured by echo Doppler ultrasound) in the femoral artery decreased and vascular resistance increased significantly in all three groups in the upright position compared with supine. Mean arterial pressure (MAP) remained unchanged in U and L and increased significantly in C in the upright versus supine position. The present study shows that all SCI individuals were able to maintain MAP by increasing leg vascular resistance during head-up tilt, despite nerve degeneration in L and lack of centrally mediated sympathetic control in all SCI individuals. Results of the present study suggest that not spinal reflexes but local (myogenic) reflex activity plays a pivotal role in peripheral vascular responses upon head-up tilt when central control mechanisms fail.
Ultra-high-frequency left prefrontal transcranial magnetic stimulation as augmentation in severely ill patients with depression: a naturalistic sham-controlled, double-blind, randomized trial.

Repetitive transcranial magnetic stimulation (rTMS) is supposed to be not as effective in severe depression as it is in medium depression. We evaluated the treatment response to an ultra-high-frequency (UHF; 30 Hz) approach, which was used to maximize the rTMS efficacy in severely ill patients.



43 severely depressed patients were included in the randomized, double-blind study and received either rTMS with 30 Hz over the left dorsolateral prefrontal cortex or sham condition for 3 weeks as an add-on therapy to stable antidepressant medication. Hamilton Depression Rating Scale (HDRS) and cognitive performance were evaluated before and after the intervention.



In the active UHF group, the HRDS score was reduced by about 7.2, whereas the sham condition showed a smaller reduction of the HDRS score with 3.9. However, lithium as a covariant was responsible for the outcome difference, not the group of stimulation. No adverse events were reported. Comparing the differences of both groups in the pre- and post-study performance in a trail-making test, a group effect for the UHF group that was not influenced by the lithium intake was observed.



A 30-Hz left prefrontal rTMS in severely depressed patients was safe and no adverse events occurred. Due to a strong effect of lithium as a covariate, we could not demonstrate favorable antidepressant effects of the UHF stimulation compared to sham. However, we found an improvement of processing speed performance in the UHF group, which covaried with improvement of psychomotor retardation.
Abnormalities of myelination in schizophrenia detected in vivo with MRI, and post-mortem with analysis of oligodendrocyte proteins

Schizophrenia unfolds during the late period of brain maturation, while myelination is still continuing. In the present study, we used MRI and T2 relaxation analysis to measure the myelin water fraction in schizophrenia. In schizophrenia (n=30) compared with healthy subjects (n=27), overall white matter showed 12% lower myelin water fraction (P=0.031), with the most prominent effects on the left genu of the corpus callosum (36% lower, P=0.002). The left anterior genu was affected in both first-episode (P=0.035) and chronic patients (P=0.011). In healthy subjects, myelin water fraction in total white matter and in frontal white matter increased with age, and with years of education, indicating ongoing maturation. In patients with schizophrenia, neither relation was statistically significant. Post-mortem studies of anterior frontal cortex demonstrated less immunoreactivity of two oligodendrocyte-associated proteins in schizophrenia (2′,3′-cyclic nucleotide 3′-phosphodiesterase by 33%, P=0.05; myelin-associated glycoprotein by 27%, P=0.14). Impaired myelination in schizophrenia could contribute to abnormalities of neural connectivity and persistent functional impairment in the illness.
Tissue plasminogen activator was cost-effective compared to streptokinase in only selected patients with acute myocardial infarction.

We sought to explore the patient-specific cost-effectiveness in a community-based sample for a therapy for which the average cost-effectiveness in a clinical trial has been well-described.



Based on a validated multivariate model, we generated predictions of the effectiveness and cost-effectiveness of t-PA compared to streptokinase on 921 consecutive patients who received thrombolytic therapy for acute myocardial infarction.



The average cost-effectiveness of t-PA was US dollar 40,140 per life-year saved. For the quartile of patients most likely to benefit, the incremental cost-effectiveness of t-PA was US dollar 15,396. However, only 44% of patients who received thrombolytic therapy had an estimated cost-effectiveness ratio below US dollar 50,000 per year of life saved; the ratio was greater than US dollar 100,000 in 37% of treated patients. Patients in the lowest quartile of expected benefit are, overall, more likely to be harmed than to benefit from t-PA.



Compared to the pattern of thrombolytic agent choice observed, targeting t-PA to the half of patients most likely to benefit could save 247 lives and US dollar 174 million nationally per year.