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A 29-year-old woman with a history of severe rheumatic mitral stenosis status post mitral valvuloplasty presented with worsening dyspnea on exertion during her second pregnancy. She underwent multimodality evaluation throughout her pregnancy, which helped to guide medical therapy and prevent unnecessary mechanical intervention and premature delivery., Competing Interests: The authors have reported that they have no relationships relevant to the contents of this article to disclose., (© 2024 The Authors.)

Background: Polymorphic ventricular tachycardia (PMVT) is an unstable and often fatal cardiac tachyarrhythmia. While there are many causes of this rhythm, including electrolyte imbalances, ischemia, and genetic disorders, iatrogenic etiologies are important to recognize. Abiraterone is an androgen synthesis antagonist effective in treating prostate cancer, but here we describe a case of severe hypokalemia secondary to abiraterone resulting in polymorphic ventricular tachycardia and cardiac arrest. While this is a potential adverse effect of the medication, severe hypokalemia causing polymorphic ventricular tachycardia and cardiac arrest, as seen in our patient's case, has not been described., Case Presentation: A 78-year-old African-American man with history of prostate cancer presents with polymorphic ventricular tachycardia and cardiac arrest. After resuscitation, he was found to be severely hypokalemic and refractory to large doses of repletion. Evaluation of secondary causes of hypokalemia identified the likely culprit to be adverse effects from prostate cancer treatment., Conclusion: A broad differential diagnosis for polymorphic ventricular tachycardia is essential in identifying and treating patients presenting in this rhythm. Here we present a case of iatrogenic polymorphic ventricular tachycardia secondary to oncologic treatment., (© 2024. The Author(s).)

Dyslipidemia is an established risk factor for cardiovascular disease (CVD), which remains the leading cause of morbidity and mortality in women globally. The incidence of dyslipidemia increases over a woman's lifespan, with adverse changes around the time of menopause. Menopause, and the years leading up to the final menstrual period, is a time of estrogen fluctuation and ultimately estrogen deficiency, which has been associated with proatherogenic changes in the lipid profile. Independent of aging, menopausal status is associated with elevations in serum total cholesterol, LDL cholesterol, apolipoproteins, and triglycerides, and decreases in HDL cholesterol (HDL-C). Emerging research also suggests that after menopause there is a loss of functional HDL cardioprotective properties. Early initiation of menopausal hormone therapy (MHT) confers a favorable effect on lipid profile, though this does not translate into improved CVD outcomes and therefore guidelines do not indicate it for primary or secondary prevention of CVD. At the time of menopause, special consideration should be given to women with conditions more associated with CVD, including polycystic ovarian syndrome, premature menopause, early menopause, premature ovarian insufficiency, and familial hypercholesterolemia. Statins remain the mainstay of dyslipidemia therapy, though novel lipid-lowering agents are emerging. This review provides an overview of lipid alterations observed during the menopausal transition, summarizes the current evidence on the role of estrogen and progestogen on lipids, identifies special populations of women at especially high risk for lipid dysregulation at menopause, and describes approaches to the screening and treatment of midlife women., Competing Interests: Declaration of competing interest The authors declare that they have no competing interest., (Copyright © 2022 Elsevier B.V. All rights reserved.)

A growing body of literature highlights the importance of recognizing adverse pregnancy outcomes (APOs) as cardiovascular risk factors when risk stratifying women for cardiovascular disease (CVD). We conducted a comprehensive review of the long term cardiovascular consequences associated with APOs including hypertensive disorders of pregnancy (HDP), preterm delivery, gestational diabetes (GDM), low birth weight and fetal growth restriction during pregnancy using electronic databases, PubMed and the Cochrane Library. Women with pregnancies complicated by HDP, preterm birth, and low birth weight are at higher risk of developing CVD than were women without APOs in the years following pregnancy. Among women with a history of multiple APOs, HDP and GDM are independent risk factors for atherosclerotic CVD. The pathophysiology leading to CVD is multifactorial, and includes both physiologic and environmental factors. APOs should be accounted for in a women's CVD risk assessment and stratification as recommended by prevention guidelines. Further research is needed to determine the underlying mechanisms that lead to the increased risk of CVD in women with APOs., Competing Interests: Declaration of competing interest The authors declare that they have no competing interest., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Referrals to cardiac rehabilitation (CR) remain low despite evidence showing reduction in cardiovascular mortality and hospital readmissions. Resident education and awareness may be an opportunity to address barriers to CR referrals., Methods: This pilot study involves 20 internal medicine residents rotating at an ambulatory primary care clinic. Voluntary surveys were sent through an online-based survey platform. Following survey completion, residents received a 10-minute scripted lecture and an educational handout outlining CR components, availability, indications, insurance eligibility criteria, and referral process. Surveys were redistributed 2 months post-education to assess changes in mean aggregate knowledge scores and attitude ratings on a 5-point Likert scale. CR referral rates of eligible patients pre- and post-education were obtained through review of electronic medical records., Results: Sixteen (80%) residents completed both pre and post surveys, and 13 (81%) reported no education on CR in the prior year. There was a significant increase in mean aggregate knowledge scores on CR components (5.1 versus 7.0, P  = 0.001), insurance coverage (2.4 versus 5.6, P < 0.001), and eligible diagnoses (7.1 versus 9.9, P  = 0.03) following education. Attitudes towards CR also improved following education, particularly in self-reported comfort level with explaining CR to patients (3.69 versus 2.06, P <0.001) and perceived familiarity with CR referral process (4.00 versus 2.18, P <0.001). CR referrals increased from 0% (0 out of 10 eligible patients) to 33% (3 out of 9 eligible patients) over a 2-month period before and after education, respectively ( P  = 0.09)., Conclusions: Internal medicine resident knowledge and attitudes towards CR significantly improved after formal education. Although there was a modest increase in the rates of CR referrals following resident education, this pilot study was not powered to detect statistical significance., Competing Interests: Dr. C. Noel Bairey Merz serves as Board of Director for iRhythm, fees paid through CSMC from Abbott Diagnostics and Sanofi. Dr. Janet Wei served on an advisory board for Abbott Vascular. All other authors have no disclosures to report., (© 2022 The Authors. Published by Elsevier B.V.)

Alzheimer's disease (AD) is the most common neurodegenerative disease and is characterized by preclinical, pre-dementia, and dementia phases. Progression of the disease leads to cognitive decline and is associated with loss of functional independence, personality changes, and behavioral disturbances. Current guidelines for AD diagnosis include the use of neuroimaging tools as biomarkers for identifying and monitoring pathological changes. Various imaging modalities, namely magnetic resonance imaging (MRI), fluorodeoxyglucose-positron emission tomography (FDG-PET) and PET with amyloid-beta tracers are available to facilitate early accurate diagnoses. Enhancing diagnosis in the early stages of the disease can allow for timely interventions that can delay progression of the disease. This paper will discuss the characteristic findings associated with each of the imaging tools for patients with AD, with a focus on FDG-PET due to its established accuracy in assisting with the differential diagnosis of dementia and discussion of other methods including MRI. Diagnostically-relevant features to aid clinicians in making a differential diagnosis will also be pointed out and multimodal imaging will be reviewed. We also discuss the role of quantification software in interpretation of brain imaging. Lastly, to guide evaluation of patients presenting with cognitive deficits, an algorithm for optimal integration of these imaging tools will be shared. Molecular imaging modalities used in dementia evaluations hold promise toward identifying AD-related pathology before symptoms are fully in evidence. The work describes state of the art functional and molecular imaging methods for AD. It will also overview a clinically applicable quantitative method for reproducible assessments of such scans in the early identification of AD.

Background: Caprylidene is a ketogen that, when metabolized, produces the ketones beta-hydroxybutyrate and acetoacetate, which can cross the blood brain barrier. It has been hypothesized that ketone bodies can be used as an alternate energy source by neurons with impaired glucose utilization. Caprylidene has been shown to improve cognition in patients with mild-to-moderate Alzheimer's disease (AD) who lacked an AD-predisposing allele (ɛ4) of the gene for apolipoprotein E. In this pilot study, we examined the effects of caprylidene on regional cerebral blood flow (rCBF) in patients with mild to moderate AD., Methods: Sixteen subjects with mild-to-moderate AD, based on NINCDS-ADRDA criteria, were enrolled in a double-blinded, placebo-controlled, randomized clinical trial. Fourteen subjects received treatment with caprylidene, and 2 subjects were given placebo. Subjects received 4 15 O-water PET scans over the course of the study to assess rCBF: once before receiving a standard caprylidene or placebo dose and 90 min after the dose, on the first day and after 45 days of daily caprylidene or placebo consumption. The scans were examined by standardized volumes of interest (sVOI) and voxel-based statistical parametric mapping (spm) methods of analysis., Results: Subjects lacking an ɛ4 allele had significantly elevated rCBF in the left superior lateral temporal cortex by sVOI analysis after adopting a caprylidene diet for 45 days (p = 0.04), which was further corroborated by spm. The anterior cerebellum, left inferior temporal cortex, and hypothalamus were also found by spm to be regions of long-term increase in rCBF in these subjects. In contrast, patients who possessed the ɛ4 allele did not display these changes in rCBF., Conclusion: Daily ingestion of caprylidene over 45 days was associated with increased blood flow in specific brain regions in patients lacking an apolipoprotein ɛ4 allele., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Rationale: Nearly 60% of U.S. children live in counties with particulate matter less than or equal to 2.5 μm in aerodynamic diameter (PM 2.5 ) concentrations above air quality standards. Understanding the relationship between ambient air pollution exposure and health outcomes informs actions to reduce exposure and disease risk., Objectives: To evaluate the association between ambient PM 2.5 levels and healthcare encounters for acute lower respiratory infection (ALRI)., Methods: Using an observational case-crossover design, subjects (n = 146,397) were studied if they had an ALRI diagnosis and resided on Utah's Wasatch Front. PM 2.5 air pollution concentrations were measured using community-based air quality monitors between 1999 and 2016. Odds ratios for ALRI healthcare encounters were calculated after stratification by ages 0-2, 3-17, and 18 or more years., Measurements and Main Results: Approximately 77% (n = 112,467) of subjects were 0-2 years of age. The odds of ALRI encounter for these young children increased within 1 week of elevated PM 2.5 and peaked after 3 weeks with a cumulative 28-day odds ratio of 1.15 per +10 μg/m 3 (95% confidence interval, 1.12-1.19). ALRI encounters with diagnosed and laboratory-confirmed respiratory syncytial virus and influenza increased following elevated ambient PM 2.5 levels. Similar elevated odds for ALRI were also observed for older children, although the number of events and precision of estimates were much lower., Conclusions: In this large sample of urban/suburban patients, short-term exposure to elevated PM 2.5 air pollution was associated with greater healthcare use for ALRI in young children, older children, and adults. Further exploration is needed of causal interactions between PM 2.5 and ALRI.

Purpose: The aim of this study was to examine the value of fluorodeoxyglucose (FDG) positron emission tomography (PET) in predicting subsequent rates of functional and cognitive decline among subjects considered cognitively normal (CN) or clinically diagnosed with mild cognitive impairment (MCI)., Methods: Analyses of 276 subjects, 92 CN subjects and 184 with MCI, who were enrolled in the Alzheimer's Disease Neuroimaging Initiative, were conducted. Functional decline was assessed using scores on the Functional Activities Questionnaire (FAQ) obtained over a period of 36 months, while cognitive decline was determined using the Alzheimer's disease Assessment Scale-Cognitive subscale (ADAS-Cog) and Mini-Mental State Examination (MMSE) scores. PET images were analyzed using clinically routine brain quantification software. A dementia prognosis index (DPI), derived from a ratio of uptake values in regions of interest known to be hypometabolic in Alzheimer's disease to regions known to be stable, was generated for each baseline FDG-PET scan. The DPI was correlated with change in scores on the neuropsychological examinations to examine the predictive value of baseline FDG-PET., Results: DPI powerfully predicted rate of functional decline among MCI patients (t = 5.75, p < 1.0E-8) and pooled N + MCI patient groups (t = 7.02, p < 1.0E-11). Rate of cognitive decline on MMSE was also predicted by the DPI among MCI (t = 6.96, p < 1.0E-10) and pooled N + MCI (t = 8.78, p < 5.0E-16). Rate of cognitive decline on ADAS-cog was powerfully predicted by the DPI alone among N (p < 0.001), MCI (t = 6.46, p < 1.0E-9) and for pooled N + MCI (t = 8.85, p = 1.1E-16)., Conclusions: These findings suggest that an index, derivable from automated regional analysis of brain PET scans, can be used to help predict rates of functional and cognitive deterioration in the years following baseline PET.

Background: Natural compounds in grapes such as resveratrol are known for their antioxidant and anti-inflammatory properties. Some studies have shown a potential role for grapes or wine in slowing cognitive decline and other effects of aging. However, well-controlled experimental data obtained in human subjects are still in need of further development. Here we aimed to systematically assess effects of grapes on regional cerebral metabolism., Methods: Ten subjects with mild decline in cognition (mean, 72.2±4.7years; 50% female) were included in this analysis. Participants were randomized into an active grape formulation arm or a placebo arm which consumed a formulation free of polyphenols for six months. Cognitive performance was measured through neuropsychological assessments performed at baseline and 6months after initiation of therapy. Changes in brain metabolism occurring with each therapy regimen were assessed by brain PET scans with the radiotracer [F-18] fluorodeoxyglucose (FDG), obtained during initial evaluation and 6months later. Standardized volumes of interest (sVOI) and statistical parametric mapping (SPM) methods were applied to FDG-PET scans to identify significant regional cerebral metabolic changes., Results: In contrast to participants taking the active grape formulation, who displayed no significant decline in metabolism, the placebo arm underwent significant metabolic decline in sVOI's of the right posterior cingulate cortex (p=0.01), and left superior posterolateral temporal cortex (p=0.04). SPM analyses also found significant declines in the placebo group, particularly in left prefrontal, cingulate, and left superior posterolateral temporal cortex (p<0.01) with stable brain metabolism in the active formulation arm. No significant differences were seen in scores on the neuropsychological battery of tests between the two groups. However, metabolism in right superior parietal cortex and left inferior anterior temporal cortex was correlated with improvements in attention/working memory, as measured with WAIS-III Digital Span within the active formulation group (r=-0.69, p=0.04)., Conclusions: The placebo arm had declines in regions of the brain known to be significantly affected in the early stages of Alzheimer's disease, while the active formulation group was spared such decline. This suggests a protective effect of grapes against early pathologic metabolic decline., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Physical activity (PA) can be neuroprotective and reduce the risk for Alzheimer's disease (AD). In assessing physical activity, caloric expenditure is a proxy marker reflecting the sum total of multiple physical activity types conducted by an individual., Objective: To assess caloric expenditure, as a proxy marker of PA, as a predictive measure of gray matter (GM) volumes in the normal and cognitively impaired elderly persons., Methods: All subjects in this study were recruited from the Institutional Review Board approved Cardiovascular Health Study (CHS), a multisite population-based longitudinal study in persons aged 65 and older. We analyzed a sub-sample of CHS participants 876 subjects (mean age 78.3, 57.5% F, 42.5% M) who had i) energy output assessed as kilocalories (kcal) per week using the standardized Minnesota Leisure-Time Activities questionnaire, ii) cognitive assessments for clinical classification of normal cognition, mild cognitive impairment (MCI), and AD, and iii) volumetric MR imaging of the brain. Voxel-based morphometry modeled the relationship between kcal/week and GM volumes while accounting for standard covariates including head size, age, sex, white matter hyperintensity lesions, MCI or AD status, and site. Multiple comparisons were controlled using a False Discovery Rate of 5 percent., Results: Higher energy output, from a variety of physical activity types, was associated with larger GM volumes in frontal, temporal, and parietal lobes, as well as hippocampus, thalamus, and basal ganglia. High levels of caloric expenditure moderated neurodegeneration-associated volume loss in the precuneus, posterior cingulate, and cerebellar vermis., Conclusion: Increasing energy output from a variety of physical activities is related to larger gray matter volumes in the elderly, regardless of cognitive status.

Recently, the National Institute on Aging and the Alzheimer's Association identified specific structural and functional neuroimaging findings as valuable markers of biological processes occurring in the human brain, especially processes that herald impending dementia caused by Alzheimer's disease (AD) in its prodromal form. In particular, the imaging modalities of magnetic resonance imaging and positron emission tomography (PET) were singled out, along with certain biomarkers in cerebrospinal fluid, to serve this purpose. We review the clinical tests available for neuropsychologic evaluation and in cases when the differential diagnosis for the causes of cognitive impairment is difficult to make, we consider biomarkers, beginning with cerebrospinal fluid, for assessment of cognitive decline. For more direct information on dementia-related pathologic changes in brain tissue, structural features observed in magnetic resonance imaging scans are regarded. We next discuss the use of single-photon emission computed tomography for evaluating functional changes. Then, pertinent to the recent National Institute on Aging and the Alzheimer's Association's consensus statement on the diagnosis of prodromal AD, we focus on assessing the cerebral metabolic changes associated with neurodegenerative diseases that are identified with fluorodeoxyglucose PET, as well as consider the most appropriate roles for amyloid imaging based on recent studies examining the use of PET with tracers having higher retention in brain tissue-harboring plaques composed of insoluble beta-amyloid. We also consider the leading causes for the current underuse of neuronuclear imaging in evaluating patients with cognitive problems, along with strategies for combating them. Finally, we suggest an overall diagnostic algorithm to guide optimal use of all the neuroimaging tools in assessing patients with cognitive decline., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Objective: Urokinase-type plasminogen activator (uPA) regulates cell migration and invasion by pericellular proteolysis and signal transduction events. We characterized the mechanisms by which uPA regulates matrix metalloproteinase-9 (MMP9) function in THP-1 monocytes., Methods and Results: In THP-1 monocytes, MMP9 production induced by urokinase was completely inhibited by the ERK1/2 inhibitor, PD98059, but not by the p38 mitogen-activated protein kinase inhibitor, SB202190. A dominant negative MEK1 adenovirus also blocked MMP9 expression. The effect of urokinase was completely suppressed by genistein and by herbimycin A indicating that tyrosine kinase(s) are required for MMP9 production. Bisindolylmaleimide, a protein kinase C (PKC) inhibitor, did not decrease MMP9 expression suggesting that PKC activation is not required. Key roles for cytosolic phospholipase A2 (PLA2) and eicosanoid production were shown by complete inhibition with methyl arachidonyl fluorophosphonate (an inhibitor of cytosolic PLA2), and indomethacin (a cyclooxygenase inhibitor), with no effect of monoalide, a secretory PLA2 inhibitor. uPA stimulated phosphorylation of cytosolic PLA2., Conclusions: Induction of MMP9 by uPA in THP-1 monocytes is via a pathway involving MEK1-ERK1/2-mediated activation of cytosolic PLA2 and eicosanoid generation. These data suggest important roles for eicosanoids in monocyte migration induced by uPA and MMP9., (Copyright (c) 2006 S. Karger AG, Basel.)