Rosiglitazone and Fenofibrate Additive Effects on Lipids

Background. To evaluate the effect of rosiglitazone, fenofibrate, or their combined use on plasma lipids in normoglycemic healthy adults. Methods and Results. Subjects were randomized in a double-blind fashion to rosiglitazone + placebo, fenofibrate + placebo, rosiglitazone + fenofibrate, or matching double placebo. The between-group difference in the change in fasting TG, high-density lipoprotein cholesterol (HDL-C), LDL-C, and plasma apolipoproteins A-I, A-II, and C-III level were compared after 12 weeks of treatment. A total of 548 subjects were screened and 41 met the inclusion criteria. After 12 weeks of therapy, the median change in the triglyceride levels showed a significant reduction ranging from 47 to 55 mg per deciliter in the fenofibrate only and rosiglitazone/fenofibrate groups compared with placebo (P = 0.0496). However, the rosiglitazone only group did not show significant change in triglyceride level. The change in the Apo AII showed increase in all the treatment groups compared with placebo (P = 0.009). There was also significant change in the Apo CIII that showed reduction of its level in the fenofibrate only and rosiglitazone/fenofibrate groups (P = 0.0003). Conclusion. Rosiglitazone does not appear to modulate hypertriglyceridemia in patients with elevated triglycerides independent of glucose metabolism

A Rare Case of Effusive Constrictive Cholesterol Pericarditis: A Case Report and Review

Effusive constrictive cholesterol pericarditis is exceedingly rare. Most cases have an unclear etiology but can be associated with rheumatoid arthritis, tuberculosis infection, and hypothyroidism. The hallmark of the effusion is the distinctively high levels of cholesterol. We present the case of a 68-year-old male with prolonged symptoms of dyspnea with associated moderate pericardial effusion that were later determined to be constrictive effusive etiology, and the patient was referred for stripping with pathologic cholesterol crystal formation on pathology review

Identification of mutations in the PYRIN-containing NLR genes (NLRP) in head and neck squamous cell carcinoma

Head and Neck Squamous Cell Carcinoma (HNSCC) encompasses malignancies that arise in the mucosa of the upper aerodigestive tract. Recent high throughput DNA sequencing revealed HNSCC genes mutations that contribute to several cancer cell characteristics, including dysregulation of cell proliferation and death, intracellular proinflammatory signaling, and autophagy. The PYRIN-domain containing NLR (Nucleotide-binding domain, Leucine rich Repeats - containing) proteins have recently emerged as pivotal modulators of cell death, autophagy, inflammation, and metabolism. Their close physiologic association with cancer development prompted us to determine whether mutations within the NLRP (PYRIN-containing NLR ) gene family were associated with HNSCC genome instability and their clinicopathologic correlations. Catastrophic mutational events underlie cancer cell genome instability and mark a point-of-no-return in cancer cell development and generation of heterogeneity. The mutation profiles of 62 patients with primary conventional type HNSCC excluding other histologic variants were analyzed. Associations were tested using Fisher's Exact test or Mann-Whitney U test. Mutations in NLRP were associated with elevated genome instability as characterized by higher mutation rates. Clinically, NLRP mutations were more frequently found in HNSCC arising in the floor of mouth (50.0%) in comparison with HNSCC at other head and neck locations (14.8%). These mutations were clustered at the leucine rich repeats region of NLRP proteins, and affected NLRP genes were mostly localized at chromosomes 11p15.4 and 19q13.42-19q13.43. Twenty novel NLRP mutations were identified in HNSCC, and mutations in this group of genes were correlated with increased cancer cell genome mutation rates, and such features could be a potential molecular biomarker of HNSCC genome instability. © 2014 Lei et al

Impact of COVID-19 on cardiovascular testing in the United States versus the rest of the world

Objectives: This study sought to quantify and compare the decline in volumes of cardiovascular procedures between the United States and non-US institutions during the early phase of the coronavirus disease-2019 (COVID-19) pandemic. Background: The COVID-19 pandemic has disrupted the care of many non-COVID-19 illnesses. Reductions in diagnostic cardiovascular testing around the world have led to concerns over the implications of reduced testing for cardiovascular disease (CVD) morbidity and mortality. Methods: Data were submitted to the INCAPS-COVID (International Atomic Energy Agency Non-Invasive Cardiology Protocols Study of COVID-19), a multinational registry comprising 909 institutions in 108 countries (including 155 facilities in 40 U.S. states), assessing the impact of the COVID-19 pandemic on volumes of diagnostic cardiovascular procedures. Data were obtained for April 2020 and compared with volumes of baseline procedures from March 2019. We compared laboratory characteristics, practices, and procedure volumes between U.S. and non-U.S. facilities and between U.S. geographic regions and identified factors associated with volume reduction in the United States. Results: Reductions in the volumes of procedures in the United States were similar to those in non-U.S. facilities (68% vs. 63%, respectively; p = 0.237), although U.S. facilities reported greater reductions in invasive coronary angiography (69% vs. 53%, respectively; p < 0.001). Significantly more U.S. facilities reported increased use of telehealth and patient screening measures than non-U.S. facilities, such as temperature checks, symptom screenings, and COVID-19 testing. Reductions in volumes of procedures differed between U.S. regions, with larger declines observed in the Northeast (76%) and Midwest (74%) than in the South (62%) and West (44%). Prevalence of COVID-19, staff redeployments, outpatient centers, and urban centers were associated with greater reductions in volume in U.S. facilities in a multivariable analysis. Conclusions: We observed marked reductions in U.S. cardiovascular testing in the early phase of the pandemic and significant variability between U.S. regions. The association between reductions of volumes and COVID-19 prevalence in the United States highlighted the need for proactive efforts to maintain access to cardiovascular testing in areas most affected by outbreaks of COVID-19 infection

Fatal Aortic Dissection in a Patient with Giant Cell Arteritis: A Case Report and Review of the Literature

Giant cell arteritis may lead to catastrophic, large-vessel complications from chronic vascular wall inflammation without prompt diagnosis and treatment. We describe a rare case of acute aortic dissection without preceding aneurysm secondary to histologically confirmed giant cell arteritis (GCA) in an 85-year-old female with a four-year history of polymyalgia rheumatica and temporal arteritis diagnosed per biopsy six months prior to presentation. The literature is reviewed and the clinical implications of this case are discussed

Case Report Fatal Aortic Dissection in a Patient with Giant Cell Arteritis: A Case Report and Review of the Literature

Giant cell arteritis may lead to catastrophic, large-vessel complications from chronic vascular wall inflammation without prompt diagnosis and treatment. We describe a rare case of acute aortic dissection without preceding aneurysm secondary to histologically confirmed giant cell arteritis (GCA) in an 85-year-old female with a four-year history of polymyalgia rheumatica and temporal arteritis diagnosed per biopsy six months prior to presentation. The literature is reviewed and the clinical implications of this case are discussed. Case Report An 85-year-old woman with a four-year history of polymyalgia rheumatica and temporal arteritis diagnosed per biopsy six months prior to presentation with an acute sensation of neck tightness with radiation to her bilateral shoulders and the epigastrium. Past medical history was significant for atrial fibrillation status following ablation, coronary artery disease status following remote myocardial infarction medically managed, hyperlipidemia, and hypertension. Her home medications included atenolol, coumadin, and prednisone 20 mg PO twice daily. She had intermittently received several rapidly tapered oral steroid courses over the preceding two years for polymyalgia rheumatica and temporal arteritis flares with resolution of clinical symptoms and normalization of acute inflammatory markers. At admission, her vital signs and cardiopulmonary exam were within normal limits. An electrocardiogram showed sinus rhythm with first-degree atrioventricular block. Cardiac biomarkers and a chest radiograph were unremarkable. Labs were significant for a stable known normochromic normocytic anemia of chronic disease (hemoglobin 10.3 g/dL), indolent chronic lymphocytic leukemia (white blood cell count of 11,400), an international normalized ratio of 2.0, and an erythrocyte sedimentation rate (ESR) of 49 mm/hr. A transthoracic echocardiogram eight months prior to admission demonstrated hyperdynamic left ventricular function with ejection fraction of 65%-70%, mild aortic insufficiency, and mild concentric left ventricular hypertrophy. Within several hours of admission, the patient was found to be unresponsive and progressively bradycardic with a depressed left ventricular function with ejection fraction of 45%. She later developed a wide complex tachycardia before terminating in pulseless electrical activity. Subsequent autopsy showed extensive granulomatous inflammation with lymphocytes, giant cells, and elastic membrane destruction in the aorta and vertebrobasilar and coronary arteries. There was evidence of early aortic root and proximal segment dissection without aneurysmal dilatation, associated with a mild pericardial effusion and a left hemothorax. Despite mild, nonobstructive atherosclerosis, there was no evidence of coronary artery occlusion or myocardial focal ischemic changes. Additionally, no large artery stenosis was appreciated

The Effects of Extended Release Niacin in Combination with Omega 3 Fatty Acid Supplements in the Treatment of Elevated Lipoprotein (a)

Objective. To assess the effectiveness of niacin/fish oil combination therapy in reducing Lipoprotein (a) [Lp(a)] levels after twelve weeks of therapy. Background. Lipoprotein (a) accumulates in atherosclerotic lesions and promotes smooth muscle cell growth and is both atherogenic and thrombogenic. A clinical trials of combination therapy for the reduction of Lp(a) has not been previously reported. Methods. The study was an observational study following subjects with an elevated Lp(a) (>70 nmol/L) to assess impact of 12 weeks of combination Omega 3FA, niacin, and the Mediterranean diet on Lp(a). Results. Twenty three patients were enrolled with 7 patients lost to follow up and 2 patients stopped due to adverse events. The average Lp(a) reduction in the remaining 14 subjects after 12 weeks of combination therapy was 23%± 17% [=.003] with a significant association of the reduction of Lp(a) with increasing baseline levels of Lp(a) [R2=0.633, =.001]. Conclusions. There was a significant reduction in Lp(a) levels with combination therapy. A more pronounced effect was noted in patients with higher baseline levels of Lp(a)

Chamber dimensions and functional assessment with coronary computed tomographic angiography as compared to echocardiography using American Society of Echocardiography guidelines

Background: The correlation between normal cardiac chamber linear dimensions measured during retrospective coronary computed tomographic angiography as compared to transthoracic echocardiography using the American Society of Echocardiography guidelines is not well established. Methods: We performed a review from January 2005 to July 2011 to identify subjects with retrospective electrocardiogram-gated coronary computed tomographic angiography scans for chest pain and transthoracic echocardiography with normal cardiac structures performed within 90 days. Dimensions were manually calculated in both imaging modalities in accordance with the American Society of Echocardiography published guidelines. Left ventricular ejection fraction was calculated on echocardiography manually using the Simpson’s formula and by coronary computed tomographic angiography using the end-systolic and end-diastolic volumes. Results: We reviewed 532 studies, rejected 412 and had 120 cases for review with a median time between studies of 7 days (interquartile range (IQR 25,75 ) = 0–22 days) with no correlation between the measurements made by coronary computed tomographic angiography and transthoracic echocardiography using Bland–Altman analysis. We generated coronary computed tomographic angiography cardiac dimension reference ranges for both genders for our population. Conclusion: Our findings represent a step towards generating cardiac chamber dimensions’ reference ranges for coronary computed tomographic angiography as compared to transthoracic echocardiography in patients with normal cardiac morphology and function using the American Society of Echocardiography guideline measurements that are commonly used by cardiologists

Real-World Performance of a Comprehensive Genomic Profiling Test Optimized for Small Tumor Samples

PURPOSE: Tissue-based comprehensive genomic profiling (CGP) is increasingly used for treatment selection in patients with advanced cancer; however, tissue availability may limit widespread implementation. Here, we established real-world CGP tissue availability and assessed CGP performance on consecutively received samples. MATERIALS AND METHODS: We conducted a post hoc, nonprespecified analysis of 32,048 consecutive tumor tissue samples received for StrataNGS, a multiplex polymerase chain reaction (PCR)-based comprehensive genomic profiling (PCR-CGP) test, as part of an ongoing observational trial (NCT03061305). Sample characteristics and PCR-CGP performance were assessed across all tested samples, including exception samples not meeting minimum input quality control (QC) requirements (\u3c 20% tumor content [TC], \u3c 2 mm tumor surface area [TSA], DNA or RNA yield \u3c 1 ng/µL, or specimen age \u3e 5 years). Tests reporting ≥ 1 prioritized alteration or meeting TC and sequencing QC were considered successful. For prostate carcinoma and lung adenocarcinoma, tests reporting ≥ 1 actionable or informative alteration or meeting TC and sequencing QC were considered actionable. RESULTS: Among 31,165 (97.2%) samples where PCR-CGP was attempted, 10.7% had \u3c 20% TC and 59.2% were small (\u3c 25 mm tumor surface area). Of 31,101 samples evaluable for input requirements, 8,089 (26.0%) were exceptions not meeting requirements. However, 94.2% of the 31,101 tested samples were successfully reported, including 80.5% of exception samples. Positive predictive value of PCR-CGP for amplification in exceptions and/or sequencing QC-failure breast cancer samples was 96.7%. Importantly, 84.0% of tested prostate carcinomas and 87.9% of lung adenocarcinomas yielded results informing treatment selection. CONCLUSION: Most real-world tissue samples from patients with advanced cancer desiring CGP are limited, requiring optimized CGP approaches to produce meaningful results. An optimized PCR-CGP test, coupled with an inclusive exception testing policy, delivered reportable results for \u3e 94% of samples, potentially expanding the proportion of CGP-testable patients and impact of biomarker-guided therapies