Citations

Background: To describe the baseline characteristics of patients with heart failure and preserved left ventricular ejection fraction enrolled in the PARAGON-HF trial (Prospective Comparison of Angiotensin Receptor Neprilysin Inhibitor With Angiotensin Receptor Blocker Global Outcomes in HFpEF) comparing sacubitril/valsartan to valsartan in reducing morbidity and mortality. Methods and Results: We report key demographic, clinical, and laboratory findings, and baseline therapies, of 4822 patients randomized in PARAGON-HF, grouped by factors that influence criteria for study inclusion. We further compared baseline characteristics of patients enrolled in PARAGON-HF with those patients enrolled in other recent trials of heart failure with preserved ejection fraction (HFpEF). Among patients enrolled from various regions (16% Asia-Pacific, 37% Central Europe, 7% Latin America, 12% North America, 28% Western Europe), the mean age of patients enrolled in PARAGON-HF was 72.7±8.4 years, 52% of patients were female, and mean left ventricular ejection fraction was 57.5%, similar to other trials of HFpEF. Most patients were in New York Heart Association class II, and 38% had ≥1 hospitalizations for heart failure within the previous 9 months. Diabetes mellitus (43%) and chronic kidney disease (47%) were more prevalent than in previous trials of HFpEF. Many patients were prescribed angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (85%), β-blockers (80%), calcium channel blockers (36%), and mineralocorticoid receptor antagonists (24%). As specified in the protocol, virtually all patients were on diuretics, had elevated plasma concentrations of N-terminal pro-B-type natriuretic peptide (median, 911 pg/mL; interquartile range, 464–1610), and structural heart disease. Conclusions: PARAGON-HF represents a contemporary group of patients with HFpEF with similar age and sex distribution compared with prior HFpEF trials but higher prevalence of comorbidities. These findings provide insights into the impact of inclusion criteria on, and regional variation in, HFpEF patient characteristics. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifier: NCT01920711.

Aims and background Id helix-loop-helix proteins function as regulators of cell growth and differentiation. However, they can induce malignant transformation when overexpressed. The EWS/ETS chimeric proteins in Ewing sarcoma act as aberrant transcription factors leading to tumorigenic processes. An enhanced expression of the Id2 gene in Ewing sarcoma cells was previously shown by gene array techniques. We investigated the expression of Id2 at the protein and gene level in Ewing sarcoma. Methods We evaluated the expression of Id2 protein using immunohistochemistry in formalin-fixed, paraffin-embedded specimens from a total of 71 cases of Ewing sarcoma. Additionally, a Ewing sarcoma cell line was examined by real-time quantitative PCR. Results Id2 expression was observed in 65 cases (91.5%) of the 71 total cases examined and a high level of Id2 expression was observed in 45 of these cases (63.8%). In tumor cells, Id2 proteins displayed cytoplasmic as well as nuclear localization. The amplification of the Id2 gene was not noted in a Ewing sarcoma cell line using real-time quantitative PCR. The crossing points of Id2 in the Ewing sarcoma cell line, control fibroblast, and osteosarcoma cell line were 18.54 ± 0.16, 18.25, and 18.34, respectively. Conclusions Our data support a role for increased Id2 protein expression in Ewing sarcoma. However, this overexpression of the Id2 protein could not be confirmed by a corresponding change at the gene level in a Ewing sarcoma cell line.

AbstractYoung hip surgeons are often faced with the decision to either perform arthroscopic surgery or a periacetabular osteotomy (PAO) in patients with symptomatic mild hip dysplasia (MHD). There is, however, a paucity of data on the results of PAO in this group. The aim of this paper is to report the results of PAOs in patients with MHD and compare those to hips with more severe forms of hip dysplasia (SHD). This data can then be used to compare emerging data reporting the results of hip arthroscopy for MHD. From January, 1996 to May, 2009, 299 hips in 268 patients were identified that underwent PAO at one institution. After removing those with <2 years of follow-up, 182 hips were followed up. The average age of the cohort was 31 years, and 85% were female. Nineteen hips with lateral center edge (LCE) angle from 18 to 25° and a Tönnis angle (TA) between 10 and 15° were considered to have MHD. This group was compared with the rest of the cohort (SHD). The mean clinical follow-up for the MHD group was 121 months. There was no significant difference in demographic variables between the groups. There were no complications in the MHD cohort. Surgical correction resulted in significant improvements in all radiographic measurements consistent with hip dysplasia in both groups. The Harris Hip Score (HHS) improved significantly in both groups ([MHD: 52–92] [SHD: 66–89]). Two hips (10.5%) in the MHD group and 15 hips (9.2%) in the SHD group underwent future THA (p = 0.69). The survivorship free from THA was 100%, 100%, and 86% at 3, 5, and 10 years, respectively, in the MHD group. The corresponding rates for hips in the control group at 3, 5, and 10 years, respectively, were 99%, 95%, and 81%. PAO in patients with MHD provides predictable improvements in pain, function, and results that are durable and comparable to hips with SHD. This data should be used to compare the early and midterm results of arthroscopic surgery performed in mildly dysplastic hips.