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Acute promyelocytic leukemia (APL) is associated with chromosomal translocation t(15;17), which results in the proliferation of morphologically abnormal promyelocytes. Gain of supernumerary copies of the 8q24 chromosomal region, which harbors MYC and PVT1, has been shown to be the most common secondary alteration in human APL. Increased MYC can accelerate the development of myeloid leukemia in APL. However, the role that the expression of the long non-coding RNA (lncRNA) PVT1 plays in the pathogenesis of APL remains largely unknown.', 'In this study, we first analyzed the lncRNA PVT1 expression level in peripheral blood cells from 28 patients with de novo APL, and significantly upregulated PVT1 was found in APL patients compared with healthy donors. We then observed significantly lower MYC and PVT1 expression during all-trans retinoic acid (ATRA)-induced differentiation and cell cycle arrest in the APL cell line. MYC knockdown in NB4 cells led to PVT1 downregulation. Moreover, PVT1 knockdown by RNA interference led to suppression of the MYC protein level, and cell proliferation was inhibited.
Is overexpression of the long non-coding RNA PVT1 correlated with leukemic cell proliferation in acute promyelocytic leukemia?

This study was designed to determine the relevance of a proposed classification for advanced heart failure (HF). Profiles based on clinical assessment of congestion and perfusion at the time of hospitalization were compared with subsequent outcomes.', 'Optimal design of therapy and trials for advanced HF remains limited by the lack of simple clinical profiles to characterize patients.', "Prospective analysis was performed for 452 patients admitted to the cardiomyopathy service at the Brigham and Women's Hospital with a diagnosis of HF. Patients were classified by clinical assessment into four profiles: profile A, patients with no evidence of congestion or hypoperfusion (dry-warm, n = 123); profile B, congestion with adequate perfusion (wet-warm, n = 222); profile C, congestion and hypoperfusion (wet-cold, n = 91); and profile L, hypoperfusion without congestion (dry-cold, n = 16). Other standard predictors of outcome were included and patients were followed for the end points of death (n = 117) and death or urgent transplantation (n = 137) at one year.", 'Survival analysis showed that clinical profiles predict outcomes in HF. Profiles B and C increase the risk of death plus urgent transplantation by univariate (hazard ratio [HR] 1.83, p = 0.02) and multivariate analyses (HR 2.48, p = 0.003). Moreover, clinical profiles add prognostic information even when limited to patients with New York Heart Association (NYHA) class III/IV symptoms (profile B: HR 2.23, p = 0.026; profile C: HR 2.73, p = 0.009).
Does clinical assessment identify hemodynamic profiles that predict outcomes in patients admitted with heart failure?

Evaluation of right ventricular (RV) function in patients with pulmonary regurgitation (PR) after tetralogy repair remains challenging because of abnormal RV loading conditions.', 'We examined 124 patients, aged 21+/-11.4 years, who had tetralogy repair at 3.7+/-3.5 years. By Doppler echocardiography, 33 patients had mild, 22 moderate, and 69 severe PR; 55 had significant tricuspid regurgitation (TR). Myocardial velocities, myocardial acceleration during isovolumic contraction (IVA), strain, and strain rate were measured at RV and LV base. Tricuspid valve annulus was measured in a 4-chamber view. QRS, QT, and JT intervals and their dispersions were measured from 12-lead electrocardiogram. IVA in the RV was lower in all patients compared with controls (0.8+/-0.4 versus 1.8+/-0.5, P<0.0001) and correlated with the severity of PR (r=-0.43, P<0.0001), whereas myocardial velocities, and strain/strain rate did not. LV IVA correlated with PR (r=-0.32, P<0.001) and with RV IVA (r=0.28, P<0.003). Patients with severe PR had a higher incidence of TR (r=0.69, P<0.0001) and lower RV IVA (1.0+/-0.4 versus 0.6+/-0.3, P<0.0001), a larger tricuspid valve ring diameter (P<0.0001), and prolonged electrical depolarization (P<0.001). Age at surgery or examination did not correlate with PR and with RV function assessed by IVA. In the RV, IVA correlated inversely with QRS duration (P<0.01).

Is pulmonary regurgitation an important determinant of right ventricular contractile dysfunction in patients with surgically repaired tetralogy of Fallot?