Thirty Years Later: Evolution of Treatment for Acute Left Main Coronary Artery Occlusion

Acute occlusion of left main coronary artery is a catastrophic event. We describe two patients with acute occlusion of the left main coronary artery treated thirty years apart. The first patient was treated in 1982 and survived the event without revascularization but developed severe heart failure. His survival was so unusual that it merited a case report at that time. The second patient was treated at the end of 2015. Early revascularization resulted in myocardial reperfusion and near normal left ventricular function. These patients exemplify the progress in therapeutic cardiology over the last 30 years

Contemporary evaluation of the causes of cardiac tamponade: Acute and long-term outcomes

Background: Cardiac tamponade is a life-threatening state that complicates various medical conditions. The contemporary interventional era may have led to changes in clinical characteristics, causes and outcomes of cardiac tamponade. Methods: We investigated all patients diagnosed with cardiac tamponade, based on clinical and echocardiographic findings, at a single medical center between the years 2000 and 2013. Data on medical history, index hospitalizations, pericardial fluid etiologies, and acute and long-term outcomes were collected. Results: Cardiac tamponade was observed in 83 patients (52% females). Major etiologies included complications of percutaneous cardiac interventions (36%) and malignancies (primarily lung cancer; 23%), infectious/inflammatory causes (15%) and mechanical complications of myocardial infarction (12%). Sixteen (19%) patients died during the index hospitalization. Acute presentation of symptoms and lower quantity of effusion were associated with in-hospital mortality (p = 0.045 and p = 0.007). Tamponade secondary to malignancy was associated with the most substantial increment in post-discharge mortality (from 16% in-hospital to 68% 1-year mortality). During the mean follow-up of 45 months, 39 (45%) patients died. Malignancies, mechanical complications of myocardial infarction and bleeding/coagulation abnormalities were etiologies associated with poor survival (80% mortality during follow-up). Tamponade secondary to complications of percutaneous cardiac interventions or infectious/inflammatory causes were associated with significantly lower mortality (28% and 17%; log rank p < 0.001). Conclusions: In a contemporary cohort, complications of percutaneous cardiac intervention replaced malignant diseases as the leading cause of cardiac tamponade. Nevertheless, these iatrogenic complications were associated with a relatively favorable outcome compared to tamponade induced by complications of myocardial infarction, coagulation abnormalities and malignant diseases.

International Consortium on Mammographic Density:methodology and population diversity captured across 22 countries

Mammographic density (MD) is a quantitative trait, measurable in all women, and is among the strongest markers of breast cancer risk. The population-based epidemiology of MD has revealed genetic, lifestyle and societal/environmental determinants, but studies have largely been conducted in women with similar westernized lifestyles living in countries with high breast cancer incidence rates. To benefit from the heterogeneity in risk factors and their combinations worldwide, we created an International Consortium on Mammographic Density (ICMD) to pool individual-level epidemiological and MD data from general population studies worldwide. ICMD aims to characterize determinants of MD more precisely, and to evaluate whether they are consistent across populations worldwide. We included 11755 women, from 27 studies in 22 countries, on whom individual-level risk factor data were pooled and original mammographic images were re-read for ICMD to obtain standardized comparable MD data. In the present article, we present (i) the rationale for this consortium; (ii) characteristics of the studies and women included; and (iii) study methodology to obtain comparable MD data from original re-read films. We also highlight the risk factor heterogeneity captured by such an effort and, thus, the unique insight the pooled study promises to offer through wider exposure ranges, different confounding structures and enhanced power for sub-group analyses

Common genetic variants and modification of penetrance of BRCA2-Associated breast cancer

The considerable uncertainty regarding cancer risks associated with inherited mutations of BRCA2 is due to unknown factors. To investigate whether common genetic variants modify penetrance for BRCA2 mutation carriers, we undertook a two-staged genome-wide association study in BRCA2 mutation carriers. In stage 1 using the Affymetrix 6.0 platform, 592,163 filtered SNPs genotyped were available on 899 young (<40 years) affected and 804 unaffected carriers of European ancestry. Associations were evaluated using a survival-based score test adjusted for familial correlations and stratified by country of the study and BRCA2*6174delT mutation status. The genomic inflation factor (λ) was 1.011. The stage 1 association analysis revealed multiple variants associated with breast cancer risk: 3 SNPs had p-values<10−5 and 39 SNPs had p-values<10−4. These variants included several previously associated with sporadic breast cancer risk and two novel loci on chromosome 20 (rs311499) and chromosome 10 (rs16917302). The chromosome 10 locus was in ZNF365, which contains another variant that has recently been associated with breast cancer in an independent study of unselected cases. In stage 2, the top 85 loci from stage 1 were genotyped in 1,264 cases and 1,222 controls. Hazard ratios (HR) and 95% confidence intervals (CI) for stage 1 and 2 were combined and estimated using a retrospective likelihood approach, stratified by country of residence and the most common mutation, BRCA2*6174delT. The combined per allele HR of the minor allele for the novel loci rs16917302 was 0.75 (95% CI 0.66-0.86, ) and for rs311499 was 0.72 (95% CI 0.61-0.85, ). FGFR2 rs2981575 had the strongest association with breast cancer risk (per allele HR = 1.28, 95% CI 1.18-1.39, ). These results indicate that SNPs that modify BRCA2 penetrance identified by an agnostic approach thus far are limited to variants that also modify risk of sporadic BRCA2 wild-type breast cancer

Brucella Endocarditis with Splenic Abscess: A Report of the First Case Diagnosed in Korea

Human brucellosis has a broad spectrum of clinical manifestations, which includes endocarditis, a focal complication that is uncommon yet responsible for the majority of associated deaths. The most successful treatment outcomes of Brucella endocarditis have been reported with usage of both antimicrobial agents and surgery. However, there are few reports on the treatment of Brucella endocarditis using antibiotics only. We report the first case in Korea of Brucella endocarditis with aortic valve vegetations and an accompanying splenic abscess, which were treated successfully with antibiotic therapy alone

LDL-Induced Impairment of Human Vascular Smooth Muscle Cells Repair Function Is Reversed by HMG-CoA Reductase Inhibition

Growing human atherosclerotic plaques show a progressive loss of vascular smooth muscle cells (VSMC) becoming soft and vulnerable. Lipid loaded-VSMC show impaired vascular repair function and motility due to changes in cytoskeleton proteins involved in cell-migration. Clinical benefits of statins reducing coronary events have been related to repopulation of vulnerable plaques with VSMC. Here, we investigated whether HMG-CoA reductase inhibition with rosuvastatin can reverse the effects induced by atherogenic concentrations of LDL either in the native (nLDL) form or modified by aggregation (agLDL) on human VSMC motility. Using a model of wound repair, we showed that treatment of human coronary VSMC with rosuvastatin significantly prevented (and reversed) the inhibitory effect of nLDL and agLDL in the repair of the cell depleted areas. In addition, rosuvastatin significantly abolished the agLDL-induced dephosphorylation of myosin regulatory light chain as demonstrated by 2DE-electrophoresis and mass spectrometry. Besides, confocal microscopy showed that rosuvastatin enhances actin-cytoskeleton reorganization during lipid-loaded-VSMC attachment and spreading. The effects of rosuvastatin on actin-cytoskeleton dynamics and cell migration were dependent on ROCK-signalling. Furthermore, rosuvastatin caused a significant increase in RhoA-GTP in the cytosol of VSMC. Taken together, our study demonstrated that inhibition of HMG-CoA reductase restores the migratory capacity and repair function of VSMC that is impaired by native and aggregated LDL. This mechanism may contribute to the stabilization of lipid-rich atherosclerotic plaques afforded by statins

Noncardiac Chest Pain: Epidemiology, Natural Course and Pathogenesis

Noncardiac chest pain is defined as recurrent chest pain that is indistinguishable from ischemic heart pain after a reasonable workup has excluded a cardiac cause. Noncardiac chest pain is a prevalent disorder resulting in high healthcare utilization and significant work absenteeism. However, despite its chronic nature, noncardiac chest pain has no impact on patients' mortality. The main underlying mechanisms include gastroesophageal reflux, esophageal dysmotility and esophageal hypersensitivity. Gastroesophageal reflux disease is likely the most common cause of noncardiac chest pain. Esophageal dysmotility affects only the minority of noncardiac chest pain patients. Esophageal hypersensitivity may be present in non-GERD-related noncardiac chest pain patients regardless if esophageal dysmotility is present or absent. Psychological co-morbidities such as panic disorder, anxiety, and depression are also common in noncardiac chest pain patients and often modulate patients' perception of disease severity

Reproductive factors and mammographic density within the International Consortium of Mammographic Density: A cross-sectional study

Background: Elevated mammographic density (MD) for a woman’s age and body mass index (BMI) is an established breast cancer risk factor. The relationship of parity, age at first birth, and breastfeeding with MD is less clear. We examined the associations of these factors with MD within the International Consortium of Mammographic Density (ICMD). Methods: ICMD is a consortium of 27 studies with pooled individual-level epidemiological and MD data from 11,755 women without breast cancer aged 35–85 years from 22 countries, capturing 40 country-& ethnicity-specific population groups. MD was measured using the area-based tool Cumulus. Meta-analyses across population groups and pooled analyses were used to examine linear regression associations of square-root (√) transformed MD measures (percent MD (PMD), dense area (DA), and non-dense area (NDA)) with parity, age at first birth, ever/never breastfed and lifetime breastfeeding duration. Models were adjusted for age at mammogram, age at menarche, BMI, menopausal status, use of hormone replacement therapy, calibration method, mammogram view and reader, and parity and age at first birth when not the association of interest. Results: Among 10,988 women included in these analyses, 90.1% (n = 9,895) were parous, of whom 13% (n = 1,286) had ≥ five births. The mean age at first birth was 24.3 years (Standard deviation = 5.1). Increasing parity (per birth) was inversely associated with √PMD (β: − 0.05, 95% confidence interval (CI): − 0.07, − 0.03) and √DA (β: − 0.08, 95% CI: − 0.12, − 0.05) with this trend evident until at least nine births. Women who were older at first birth (per five-year increase) had higher √PMD (β:0.06, 95% CI:0.03, 0.10) and √DA (β:0.06, 95% CI:0.02, 0.10), and lower √NDA (β: − 0.06, 95% CI: − 0.11, − 0.01). In stratified analyses, this association was only evident in women who were post-menopausal at MD assessment. Among parous women, no associations were found between ever/never breastfed or lifetime breastfeeding duration (per six-month increase) and √MD. Conclusions: Associations with higher parity and older age at first birth with √MD were consistent with the direction of their respective associations with breast cancer risk. Further research is needed to understand reproductive factor-related differences in the composition of breast tissue and their associations with breast cancer risk

Vascular Remodeling in Health and Disease

The term vascular remodeling is commonly used to define the structural changes in blood vessel geometry that occur in response to long-term physiologic alterations in blood flow or in response to vessel wall injury brought about by trauma or underlying cardiovascular diseases.1, 2, 3, 4 The process of remodeling, which begins as an adaptive response to long-term hemodynamic alterations such as elevated shear stress or increased intravascular pressure, may eventually become maladaptive, leading to impaired vascular function. The vascular endothelium, owing to its location lining the lumen of blood vessels, plays a pivotal role in regulation of all aspects of vascular function and homeostasis.5 Thus, not surprisingly, endothelial dysfunction has been recognized as the harbinger of all major cardiovascular diseases such as hypertension, atherosclerosis, and diabetes.6, 7, 8 The endothelium elaborates a variety of substances that influence vascular tone and protect the vessel wall against inflammatory cell adhesion, thrombus formation, and vascular cell proliferation.8, 9, 10 Among the primary biologic mediators emanating from the endothelium is nitric oxide (NO) and the arachidonic acid metabolite prostacyclin [prostaglandin I2 (PGI2)], which exert powerful vasodilatory, antiadhesive, and antiproliferative effects in the vessel wall