Impact of Baseline Heart Failure on Acute Pulmonary Embolism Risk Stratification and Clinical Outcomes.

Among patients with acute pulmonary embolism (PE), abnormal cardiac biomarkers and elevated right ventricular to left ventricular (RV/LV) diameter ratio are associated with increased morbidity and mortality. However, subjects with baseline heart failure (HF) have abnormalities in cardiac chamber dimensions and biomarkers. We sought to describe risk stratification variables in a cohort with acute PE and categorized HF status as no HF, HF with reduced ejection fraction (HFrEF), or HF with preserved ejection fraction (HFpEF). In total, 182 subjects were identified for this study, of whom 142 were categorized as having no HF, 16 as having HFrEF, and 24 as having HFpEF. The median age was 65 years [interquartile range 51 to 75 years], and 43% were male. Subjects with HFrEF had significantly greater LV diameters and significantly lower RV/LV diameter ratio (no HF 0.94, HFrEF 0.65, HFpEF 0.89, p = 0.002). Subjects with HFrEF also had significantly higher B-type natriuretic peptide levels (no HF 112 pg/mL, HFrEF 835 pg/mL, HFpEF 241 pg/mL, p <0.001) and higher 90-day mortality rates. Among subjects with acute PE, those with baseline HFrEF had significantly greater LV diameter and lower RV/LV diameter ratio than those of patients with HFpEF or no HF. In addition, subjects with HFrEF had significantly higher B-type natriuretic peptide levels and worse survival at 90 days. In conclusion, these results indicate that PE risk stratification using current guidelines, especially reliance on RV/LV ratio, is inaccurate among subjects with baseline HFrEF.

Nonhealing venous ulcer in a patient with dystrophic soft tissue calcification.

Venous leg ulcers (VLUs) are lesions of the skin found in regions of venous hypertension. VLUs that fail to heal can become chronic, especially because of calcified deposits in the bed of the ulcer. The unclear mechanism behind the cause of calcification poses a challenge when approaching diagnosis and management. In the present report, we discuss the case of a 58-year-old woman who had presented with a chronic VLU that was resistant to healing despite numerous interventions. During a 3-year period, a multidisciplinary team was involved to provide medical and surgical care. Eventually, she was found to have dystrophic calcification of the VLU.

Impact of Intramyocardial Hemorrhage on Clinical Outcomes in ST-Elevation Myocardial Infarction: A Systematic Review and Meta-analysis.

Background: Intramyocardial hemorrhage (IMH) occurs after ST-elevation myocardial infarction (STEMI) and has been documented using cardiac magnetic resonance imaging. The prevalence and prognostic significance of IMH are not well described, and the small sample size has limited prior studies. Methods: We performed a comprehensive literature search of multiple databases to identify studies that compared outcomes in STEMI patients with or without IMH. The outcomes studied were major adverse cardiovascular events (MACE), infarct size, thrombolysis in myocardial infarction (TIMI) flow after percutaneous coronary intervention (PCI), left ventricular end-diastolic volume (LVEDV), left ventricular ejection fraction (LVEF), and mortality. Odds ratios (ORs) and standardized mean differences with corresponding 95% CIs were calculated using a random effects model. Results: Eighteen studies, including 2824 patients who experienced STEMI (1078 with IMH and 1746 without IMH), were included. The average prevalence of IMH was 39%. There is a significant association between IMH and subsequent MACE (OR, 2.63; 95% CI, 1.79-3.86; P < .00001), as well as IMH and TIMI grade <3 after PCI (OR, 1.75; 95% CI, 1.14-2.68; P = .05). We also found a significant association between IMH and the use of glycoprotein IIb/IIIa inhibitors (OR, 2.34; 95% CI, 1.42-3.85; P = .0008). IMH has a positive association with infarct size (standardized mean difference, 2.19; 95% CI, 1.53-2.86; P < .00001) and LVEDV (standardized mean difference, 0.7; 95% CI, 0.41-0.99; P < .00001) and a negative association with LVEF (standardized mean difference, -0.89; 95% CI, -1.15 to -0.63; P = .01). Predictors of IMH include male sex, smoking, and left anterior descending infarct. Conclusions: Intramyocardial hemorrhage is prevalent in approximately 40% of patients who experience STEMI. IMH is a significant predictor of MACE and is associated with larger infarct size, higher LVEDV, and lower LVEF after STEMI.

Trends in pulmonary embolism mortality rates by age group in the United States, 1999-2019.

Introduction: Acute pulmonary embolism (PE) is a major cause of mortality in the United States. Recent reports indicate that PE-related mortality rates have increased among individuals younger than 65 years old. It remains unclear whether this increase in PE-related mortality is evenly distributed. A narrowly focused and clinically meaningful age group analysis is necessary. Methods: Death certificate data from the Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research database were examined to determine all-cause PE mortality trends from 1999 to 2019 among adults 25-39, 40-54, 55-69, 70-84, and ≥85 years old. The crude death rates for individual years and annual percentage change (APC) were calculated to determine trends. Results: PE-related mortality rates increased among those 25-39, 40-54, and 55-69. Among individuals 25-39 years old, death rate increased from 1.8 to 2.0 (APC 0.7 [95% confidence interval (CI) 0.2 to 1.1]) between 1999 and 2014 and continued to increase from 2.0 to 2.4 (APC 4.1 [95% CI 1.8 to 6.5]) between 2014 and 2019. Among those 40-54 years old, the crude death rate increased from 5.7 to 7.5 (APC 2.0 [95% CI, 1.6 to 2.5]) between 2007 and 2019. Among those 55-69 years old the crude death rate increased from 15.6 to 18.5 (APC 2.2 [95% CI, 1.9 to 2.5]) between 2010 and 2019. Recent death rates decreased or plateaued among individuals older than 70. Conclusions: Individuals younger than 70 years had increase in PE-related mortality between 1999 and 2019 with marked increase among those 25-39 years old.

The nucleolus as a polarized coaxial cable in which the rDNA axis is surrounded by dynamic subunit-specific phases.

In ribosomal DNA (rDNA) repeats, sequences encoding small-subunit (SSU) rRNA precede those encoding large-subunit (LSU) rRNAs. Processing the composite transcript and subunit assembly requires >100 subunit-specific nucleolar assembly factors (AFs). To investigate the functional organization of the nucleolus, we localized AFs in S. cerevisiae in which the rDNA axis was "linearized" to reduce its dimensionality, thereby revealing its coaxial organization. In this situation, rRNA synthesis and processing continue. The axis is embedded in an inner layer/phase of SSU AFs that is surrounded by an outer layer/phase of LSU AFs. When subunit production is inhibited, subsets of AFs differentially relocate between the inner and outer layers, as expected if there is a cycle of repeated relocation whereby "latent" AFs become "operative" when recruited to nascent subunits. Recognition of AF cycling and localization of segments of rRNA make it possible to infer the existence of assembly intermediates that span between the inner and outer layers and to chart the cotranscriptional assembly of each subunit. AF cycling also can explain how having more than one protein phase in the nucleolus makes possible "vectorial 2-phase partitioning" as a driving force for relocation of nascent rRNPs. Because nucleoplasmic AFs are also present in the outer layer, we propose that critical surface remodeling occurs at this site, thereby partitioning subunit precursors into the nucleoplasm for post-transcriptional maturation. Comparison to observations on higher eukaryotes shows that the coaxial paradigm is likely to be applicable for the many other organisms that have rDNA repeats.