Abstract 17058: Phenotypically Sex Differences in Transthyretin Amyloidosis V122I Mutation Patients

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Victoria Kalinoski-Dubose ◽  
Samantha LoRusso ◽  
Yvonne Efebera ◽  
Samir Parikh ◽  
Salem almaani ◽  
...  
Keyword(s):  
Sex Differences ◽  
Ejection Fraction ◽  
Symptom Onset ◽  
Posterior Wall ◽  
The United States ◽  
Sensory Response ◽  
Common Mutation ◽  
Transthyretin Amyloidosis ◽  
Asymptomatic Patients ◽  
The Ohio State University

Introduction: Hereditary transthyretin amyloidosis (ATTR) is an autosomal dominant disease, in which destabilized transthyretin protein misfolds and deposits in tissue leading to organ dysfunction. The most common mutation in the United States, transthyretin valine 122 isoleucine (V122I), primarily affects African Americans and is historically associated with cardiomyopathy phenotype in men. Recent studies have described a mixed V122I phenotype with both cardiomyopathy and polyneuropathy. Sex differences in V122I presentations have yet to be examined. Methods: We identified 38 ATTR patients treated at The Ohio State University with genetic testing demonstrating V122I mutation (31.6% female). Clinical data was analyzed for cardiac and nerve involvement including cardiac biopsy or nuclear pyrophosphate scan, echocardiography - interventricular septal thickness (IVSd), posterior wall thickness (PWd), ejection fraction (EF), and electromyography (EMG). Cohorts were divided by sex. Unpaired t-tests were used to calculate statistics. Asymptomatic patients (n=2) were not included. Results: In women with V122I ATTR, the clinical phenotypes were polyneuropathy (75%) and cardiomyopathy (25%) with symptom onset most often in the fourth or fifth decade of life. In men with V122I ATTR, the most common phenotypes were cardiomyopathy (52%) and mixed cardiomyopathy/polyneuropathy (48%) with symptom onset in the seventh and eighth decades of life. In affected individuals, EMG data revealed generalized neuropathy with reduced or absent sural nerve sensory response. Carpal tunnel syndrome, often due to thickening of the transverse ligament, was more common in men than women (84% versus 36%). Men had significant cardiac differences compared to women with thickened ventricles (IVSd 19.9 mm vs 12.5 mm, p<0.001 and PWd 17.3 mm vs 12.1 mm, p<0.001) and decreased ejection fraction (40% versus 55%, p=0.008). Conclusion: Based on our cohort, female ATTR V122I patients present predominantly with polyneuropathy phenotype at a younger age, and males present with predominantly cardiovascular or mixed phenotype. Recognizing these different sex phenotypes in ATTR V122I will improve diagnosis and treatment of patients.

P336A descriptive analysis of patients with wild-type ATTR cardiomyopathy from the transthyretin amyloidosis outcomes survey

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
P Garcia-Pavia ◽  
M Grogan ◽  
A Dispenzieri ◽  
R Mundayat ◽  
L Amass ◽  
...  
Keyword(s):  
Symptom Onset ◽  
Cardiac Disease ◽  
The United States ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Motor Neuropathy ◽  
Wild Type ◽  
Transthyretin Amyloidosis ◽  
Ventricular Ejection Fraction ◽  
Attr Amyloidosis

Abstract Introduction Transthyretin amyloidosis (ATTR amyloidosis) is a rare, life-threatening disorder caused by the deposition of amyloid fibrils composed of misfolded transthyretin (TTR). ATTR amyloidosis may arise from mutations in TTR or from aggregation of wild-type TTR (ATTRwt). ATTR amyloidosis with predominantly symptoms of cardiomyopathy (ATTR-CM) includes both hereditary and wild-type forms of the disease. Purpose To describe clinical history and disease presentation in a large population of patients with wild-type ATTR-CM from the Transthyretin Amyloidosis Outcomes Survey (THAOS). THAOS is an ongoing, global, longitudinal, observational survey of patients with ATTR amyloidosis, including both inherited and wild-type disease, and asymptomatic patients with TTR mutations. Methods Data from ATTRwt patients were extracted from THAOS (cut-off date: January 16, 2019) and demographic and clinical characteristics reported using descriptive statistics. Results There were 758 ATTRwt patients in THAOS (95% male). The majority of patients (69.3%) were in the United States, with the remainder in Italy (11.1%), Germany (7.3%), Spain (5.3%), and other countries (7.1%). Most patients (86.3%) were Caucasian, with 3.3% being of African Descent and 3.1% being of other races/ethnicities (7.4% missing data). The median (10–90th percentile) age at symptom onset was 69.7 (54.0–81.3) years and the median (10–90th percentile) time from symptom onset to diagnosis was 3.9 (0.1–17.8) years. Median (10–90th percentile) age at enrollment in THAOS was 76.4 (67.2–85.2) years. Nearly all subjects had either a cardiac (59.6%) or mixed cardiac and neurologic (36.5%) phenotype. At enrollment, 97.1% (577 of 594 patients assessed) had an abnormal ECG, with the prevalence of low voltage being 20.8% (115 of 552) and prevalence of left-ventricular hypertrophy being 2.1% (16 of 758). Atrial fibrillation was documented in 55% of patients (208 of 378). The mean (standard deviation [SD]) left-ventricular septum thickness was 17.5 (3.5) mm (n=505; 94.9% with thickness >12 mm) and mean (SD) left-ventricular ejection fraction (LVEF) was 48.3% (13.2) (n=511; 48.0% with LVEF <50.0%). Other signs and symptoms at enrollment were compatible with a sensory neuropathy in 54.2% of patients, autonomic neuropathy in 33.5% of patients, and motor neuropathy in 29.1% of patients. Gastrointestinal symptoms related to ATTR amyloidosis were present in 10.4% of patients. Conclusions Although patients with wild-type ATTR-CM tend to be older Caucasian men with a mostly cardiac disease phenotype, the clinical spectrum of ATTRwt is heterogeneous and differs from the classic phenotype. Our findings show that ATTRwt should not be considered an exclusively cardiac disease and there is a need for both cardiologic and neurologic assessment of these patients. Further study is needed to determine if the non-cardiac manifestations are due to amyloidosis or more common causes in this older population. Acknowledgement/Funding This study was sponsored by Pfizer.

Sex Differences in Mass Media Preferences Across Four Asian Countries

2011 ◽  
Vol 23 (4) ◽  
pp. 186-191 ◽  
Author(s):  
Malini Ratnasingam ◽  
Lee Ellis
Keyword(s):  
United States ◽  
Sex Differences ◽  
Mass Media ◽  
The United States ◽  
Female Students ◽  
The Internet ◽  
Evolutionary Explanation ◽  
Asian Countries ◽  
The World ◽  
Media Preferences

Background. Nearly all of the research on sex differences in mass media utilization has been based on samples from the United States and a few other Western countries. Aim. The present study examines sex differences in mass media utilization in four Asian countries (Japan, Malaysia, South Korea, and Singapore). Methods. College students self-reported the frequency with which they accessed the following five mass media outlets: television dramas, televised news and documentaries, music, newspapers and magazines, and the Internet. Results. Two significant sex differences were found when participants from the four countries were considered as a whole: Women watched television dramas more than did men; and in Japan, female students listened to music more than did their male counterparts. Limitations. A wider array of mass media outlets could have been explored. Conclusions. Findings were largely consistent with results from studies conducted elsewhere in the world, particularly regarding sex differences in television drama viewing. A neurohormonal evolutionary explanation is offered for the basic findings.

Combination of Huangqi Granule and Rosuvastatin Improves the Cardiac Function in Heart Failure

2020 ◽  
Vol 19 (2) ◽  
pp. 181-187
Author(s):  
Jing Li ◽  
Yun Zhang ◽  
Weizhong Huangfu ◽  
Yuhong Ma
Keyword(s):  
Heart Failure ◽  
Left Ventricular Ejection Fraction ◽  
Ejection Fraction ◽  
Wall Thickness ◽  
Posterior Wall ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Model Group ◽  
Ventricular Ejection Fraction ◽  
Posterior Wall Thickness

Using rat models of heart failure, we evaluated the effects of rosuvastatin and Huangqi granule alone and in combination on left ventricular end-diastolic dimension, left ventricular end-systolic dimension, left ventricular ejection fraction, left ventricular posterior wall thickness at end-diastole, and left ventricular posterior wall thickness at end-systole. Results showed that left ventricular end-diastolic dimension, left ventricular end-systolic dimension in the rosuvastatin + Huangqi granule group were significantly decreased (P ‹ 0.01), while left ventricular ejection fraction, left ventricular posterior wall thickness at end-diastole and left ventricular posterior wall thickness at end-systole were significantly increased (P ‹ 0.05). The serum IL-2, IFN-β, and TNF-α in rosuvastatin + Huangqi granule group were significantly lower than those in model group (P ‹ 0.05). However, the levels of S-methylglutathione and superoxide dismutase in rosuvastatin + Huangqi granule group were significantly higher, while nitric oxide was significantly lower than that in the model group (P ‹ 0.05). Also, compared to the model group, the apoptosis rate, and the autophagy protein LC3-II in the cardiomyocytes of rosuvastatin + Huangqi granule group was significantly decreased (P ‹ 0.01), while the level of p62 protein was significantly increased (P ‹ 0.01). The levels of AMPK and p-AMPK in cardiomyocytes were significantly lower in rosuvastatin + Huangqi granule group; however, the levels of mTOR and p-mTOR showed an opposite trend (P ‹ 0.05). To sum up, rosuvastatin + Huangqi granule could improve the cardiac function, decrease the level of oxidative stress, and inflammatory cytokines in rats with HF. The possible underlying mechanism might be inhibition of autophagy and reduced apoptosis in cardiomyocytes by regulating AMPK-mTOR signaling pathway.

scholarly journals Sources of SARS-CoV-2 and Other Microorganisms in Dental Aerosols

2021 ◽  
pp. 002203452110159
Author(s):  
A.P. Meethil ◽  
S. Saraswat ◽  
P.P. Chaudhary ◽  
S.M. Dabdoub ◽  
P.S. Kumar
Keyword(s):  
Infection Control ◽  
Dental Treatment ◽  
Quantitative Polymerase Chain Reaction ◽  
The United States ◽  
Control Measures ◽  
Personal Protection ◽  
Personal Protection Equipment ◽  
Linear Discriminant ◽  
16S Sequencing ◽  
Asymptomatic Patients

On March 16, 2020, 198,000 dentists in the United States closed their doors to patients, fueled by concerns that aerosols generated during dental procedures are potential vehicles for transmission of respiratory pathogens through saliva. Our knowledge of these aerosol constituents is sparse and gleaned from case reports and poorly controlled studies. Therefore, we tracked the origins of microbiota in aerosols generated during ultrasonic scaling, implant osteotomy, and restorative procedures by combining reverse transcriptase quantitative polymerase chain reaction (to identify and quantify SARS-CoV-2) and 16S sequencing (to characterize the entire microbiome) with fine-scale enumeration and source tracking. Linear discriminant analysis of Bray-Curtis dissimilarity distances revealed significant class separation between the salivary microbiome and aerosol microbiota deposited on the operator, patient, assistant, or the environment ( P < 0.01, analysis of similarities). We also discovered that 78% of the microbiota in condensate could be traced to the dental irrigant, while saliva contributed to a median of 0% of aerosol microbiota. We also identified low copy numbers of SARS-CoV-2 virus in the saliva of several asymptomatic patients but none in aerosols generated from these patients. Together, the bacterial and viral data encourage us to conclude that when infection control measures are used, such as preoperative mouth rinses and intraoral high-volume evacuation, dental treatment is not a factor in increasing the risk for transmission of SARS-CoV-2 in asymptomatic patients and that standard infection control practices are sufficiently capable of protecting personnel and patients from exposure to potential pathogens. This information is of immediate urgency, not only for safe resumption of dental treatment during the ongoing COVID-19 pandemic, but also to inform evidence-based selection of personal protection equipment and infection control practices at a time when resources are stretched and personal protection equipment needs to be prioritized.

scholarly journals Arrest of atherosclerosis progression after interruption of GH replacement in adults with congenital isolated GH deficiency

2012 ◽  
Vol 166 (6) ◽  
pp. 977-982 ◽  
Author(s):  
Vanessa P Araujo ◽  
Manuel H Aguiar-Oliveira ◽  
Joselina L M Oliveira ◽  
Hertaline M N Rocha ◽  
Carla R P Oliveira ◽  
...  
Keyword(s):  
Ejection Fraction ◽  
Diastolic Function ◽  
Gh Deficiency ◽  
Systolic Function ◽  
Receptor Gene ◽  
Intima Media Thickness ◽  
Posterior Wall ◽  
Left Ventricular ◽  
Carotid Imt ◽  
Gh Replacement

ObjectiveGH replacement therapy (GHRT) in adult-onset GH deficiency (AOGHD) reduces carotid intima-media thickness (IMT) and increases myocardial mass, with improvement of systolic and diastolic function. These observations have reinforced the use of GHRT on AOGHD. Conversely, we have previously reported that in adults with lifetime congenital and severe isolated GH deficiency (IGHD) due to a mutation in GHRH receptor gene (GHRHR), a 6-month treatment with depot GH increased carotid IMT, caused the development of atherosclerotic plaques, and an increase in left ventricular mass index (LVMI), posterior wall, and septal thickness and ejection fraction. Such effects persisted 12 months after treatment (12-month washout – 12mo).MethodsWe have studied the cardiovascular status (by echocardiography and carotid ultrasonography) of these subjects 60 months after completion of therapy (60-month washout – 60mo).ResultsCarotid IMT reduced significantly from 12 to 60mo, returning to baseline (pre-therapy) value. The number of individuals with plaques was similar at 12 and 60mo, remaining higher than pre-therapy. LVMI, relative posterior wall thickness, and septum thickness did not change between 12 and 60mo, but absolute posterior wall increased from 12 to 60mo. Systolic function, evaluated by ejection fraction and shortening fraction, was reduced at 60mo in comparison with 12mo returning to baseline levels. The E/A wave ratio (expression of diastolic function) decreased at 60mo compared with both 12mo and baseline.ConclusionsIn adults with lifetime congenital IGHD, the increase in carotid IMT elicited by GHRT was transitory and returned to baseline 5 years after therapy discontinuation. Despite this, the number of subjects with plaques remained stable at 60mo and higher than at baseline.

Abstract WP178: Acute Stroke Ischemic Symptom Onset-to-Arrival Time in Michigan Hospitals

Stroke ◽  
2016 ◽  
Vol 47 (suppl_1) ◽  
Author(s):  
Muhammad U Farooq ◽  
Kathie Thomas
Keyword(s):  
African American ◽  
Ischemic Stroke ◽  
Acute Stroke ◽  
Patient Outcomes ◽  
Symptom Onset ◽  
Arrival Time ◽  
Heart Association ◽  
The United States ◽  
Stroke Patients ◽  
White Patients

Objectives: Stroke is the fifth-leading cause of death and the leading cause of disability in the United States. One of the primary goals of the American Heart Association/American Stroke Association is to increase the number of acute stroke patients arriving at emergency departments (EDs) within 1-hour of symptom onset. Earlier treatment with thrombolysis in patients with acute ischemic stroke translates into improved patient outcomes. The objective of this abstract is to examine the association between the use of emergency medical services (EMS) and symptom onset-to-arrival time in patients with ischemic stroke. Methods: A retrospective review of ischemic stroke patients (n = 8873) from 25 Michigan hospitals from January 2012-December 2014 using Get With the Guidelines databases was conducted. Symptom onset-to-ED arrival time and arrival mode were examined. Results: It was found that 17.4% of ischemic stroke patients arrived at the hospitals within 1-hour of symptom onset. EMS transported 69.1% of patients who arrived within 1-hour of symptom onset. During this 1-hour period African American patients (22%) were less likely to use EMS transportation as compared to White patients (72%). The majority of patients, 41.8%, arrived after 6-hours of symptom onset. EMS transported only 40% of patients who arrived after 6-hours of symptom onset. As before, during this 6-hour period African American patients (20%) were also less likely to use EMS transportation as compared to White patients (75%). Symptom onset-to-ED arrival time was shorter for those patients who used EMS. The median pre-hospital delay time was 2.6 hours for those who used EMS versus 6.2 hours for those who did not use EMS. Conclusions: The use of EMS is associated with a decreased pre-hospital delay, early treatment with thrombolysis and improved patient outcomes in ischemic stroke patients. Community interventions should focus on creating awareness especially in minority populations about stroke as a neurological emergency and encourage EMS use amongst stroke patients.

Achieving More Rapid Door-to-Needle Times and Improved Outcomes in Acute Ischemic Stroke in a Nationwide Quality Improvement Intervention

Stroke ◽  
2021 ◽  
Author(s):  
Ying Xian ◽  
Haolin Xu ◽  
Eric E. Smith ◽  
Jeffrey L. Saver ◽  
Mathew J. Reeves ◽  
...  
Keyword(s):  
United States ◽  
Quality Improvement ◽  
Ischemic Stroke ◽  
Thrombolytic Therapy ◽  
Phase I ◽  
Acute Ischemic Stroke ◽  
Symptom Onset ◽  
Odds Ratio ◽  
Adjusted Odds Ratio ◽  
The United States

Background and Purpose: The benefits of tPA (tissue-type plasminogen activator) in acute ischemic stroke are time-dependent. However, delivery of thrombolytic therapy rapidly after hospital arrival was initially occurring infrequently in hospitals in the United States, discrepant with national guidelines. Methods: We evaluated door-to-needle (DTN) times and clinical outcomes among patients with acute ischemic stroke receiving tPA before and after initiation of 2 successive nationwide quality improvement initiatives: Target: Stroke Phase I (2010–2013) and Target: Stroke Phase II (2014–2018) from 913 Get With The Guidelines-Stroke hospitals in the United States between April 2003 and September 2018. Results: Among 154 221 patients receiving tPA within 3 hours of stroke symptom onset (median age 72 years, 50.1% female), median DTN times decreased from 78 minutes (interquartile range, 60–98) preintervention, to 66 minutes (51–87) during Phase I, and 50 minutes (37–66) during Phase II ( P <0.001). Proportions of patients with DTN ≤60 minutes increased from 26.4% to 42.7% to 68.6% ( P <0.001). Proportions of patients with DTN ≤45 minutes increased from 10.1% to 17.7% to 41.4% ( P <0.001). By the end of the second intervention, 75.4% and 51.7% patients achieved 60-minute and 45-minute DTN goals. Compared with the preintervention period, hospitals during the second intervention period (2014–2018) achieved higher rates of tPA use (11.7% versus 5.6%; adjusted odds ratio, 2.43 [95% CI, 2.31–2.56]), lower in-hospital mortality (6.0% versus 10.0%; adjusted odds ratio, 0.69 [0.64–0.73]), fewer bleeding complication (3.4% versus 5.5%; adjusted odds ratio, 0.68 [0.62–0.74]), and higher rates of discharge to home (49.6% versus 35.7%; adjusted odds ratio, 1.43 [1.38–1.50]). Similar findings were found in sensitivity analyses of 185 501 patients receiving tPA within 4.5 hours of symptom onset. Conclusions: A nationwide quality improvement program for acute ischemic stroke was associated with substantial improvement in the timeliness of thrombolytic therapy start, increased thrombolytic treatment, and improved clinical outcomes.

Abstract 17470: Racial Disparities in Goal Directed Medical Therapy in Patients With Systolic Heart Failure- A Single Center Study

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Ayesha Azmeen ◽  
Naga Vaishnavi Gadela ◽  
Vergara Cunegundo
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Racial Disparities ◽  
Beta Blockers ◽  
Systolic Heart Failure ◽  
The United States ◽  
Clinical Syndrome ◽  
Single Center ◽  
Geographic Variations ◽  
Reduced Ejection Fraction

Introduction: Heart failure(HF) is a clinical syndrome that is widely prevalent affecting approximately 6.5 million people in the United States. It accounts for the ever-rising health care costs in the US due to recurrent hospitalizations. Despite advancements in medical management, the mortality and the rate of hospitalizations continues to be high with geographic variations and racial disparities. Through this descriptive study, we sought to analyze the health disparities among Hispanic, African American (AA) and Caucasian population in a single-center. Methods: We identified a total of 178 patients with HF with reduced ejection fraction from our outpatient clinic by utilizing the ICD-10 codes. Patients with ejection fraction >50% have been excluded. A retrospective chart review of their ethnic background, medications, and number of heart failure exacerbations per year has been performed. Results: 178 patients (mean age 62 years, 35.56% of females) including Hispanics (n=102), AA(n=44), and Caucasians (n=32) were included in the study. Although all patients were started on Beta-blockers, only 76.4% and 37.2% of Hispanics were started on ACEi/ARBs and spironolactone respectively. Similarly, 72.7% and 45.4% of AA were started on ACEi/ARBs and spironolactone respectively. This is in contrast to Caucasians population, where a majority of patients were on started on GDMT; 90% and 75% were started on ACEi/ARBs and spironolactone respectively. This was also reflected by the number of admissions due to HF exacerbations which ranged from 2-4/year for Hispanics and AA populations and 0-1/year for Caucasians. Conclusions: GDMT for HF is known to reduce heart failure exacerbations, mortality and the ever rising cost of the healthcare system. We have observed that despite recommendations to initiate GDMT in all patients with HF with reduced ejection fraction, racial disparities exist. Physicians should be mindful of initiating GDMT in all patients.

Sign in / Sign up

Export Citation Format

Share Document