bluuebunny/crossref_metadata_2025 huggingface dataset:
Factors Associated with Gestational Diabetes Mellitus: A Meta-Analysis
Authors: Zhang Yu , Xiao Cheng-Ming , Zhang Yan , Chen Qiong , Zhang Xiao-Qin , Li Xue-Feng , Shao Ru-Yue , Gao Yi-Meng
Published: May 2021

Gestational diabetes mellitus (GDM) is a major public health issue, and the aim of the present study was to identify the factors associated with GDM. Databases were searched for observational studies until August 20, 2020. Pooled odds ratios (ORs) were calculated using fixed- or random-effects models. 103 studies involving 1,826,454 pregnant women were identified. Results indicated thatmaternal age≥25years (OR: 2.466, 95% CI: (2.121, 2.866)), prepregnancy overweight or obese (OR: 2.637, 95% CI: (1.561, 4.453)), family history of diabetes (FHD) (OR: 2.326, 95% CI: (1.904, 2.843)), history of GDM (OR: 21.137, 95% CI: (8.785, 50.858)), macrosomia (OR: 2.539, 95% CI: (1.612, 4.000)), stillbirth (OR: 2.341, 95% CI: (1.435, 3.819)), premature delivery (OR: 3.013, 95% CI: (1.569, 5.787)), and pregestational smoking (OR: 2.322, 95% CI: (1.359, 3.967)) increased the risk of GDM with allP<0.05, whereas history of congenital anomaly and abortion, and HIV status showed no correlation with GDM (P>0.05). Being primigravida (OR: 0.752, 95% CI: (0.698, 0.810),P<0.001) reduced the risk of GDM. The factors influencing GDM includedmaternal age≥25, prepregnancy overweight or obese, FHD, history of GDM, macrosomia, stillbirth, premature delivery, pregestational smoking, and primigravida.
Pain Management in People with Diabetes-Related Chronic Limb-Threatening Ischemia
Authors: Jiang Xiaoyan , Yuan Yi , Ma Yu , Zhong Miao , Du Chenzhen , Boey Johnson , Armstrong David G. , Deng Wuquan , Duan Xiaodong
Published: May 2021

Management of neuropathic pain in people with diabetes has been widely investigated. However, little attention was paid to address ischemic-related pain in patients with diabetes mellitus who suffered from chronic limb-threatening ischemia (CLTI), the end stage of lower extremity arterial disease (LEAD). Pain management has a tremendous influence on patients’ quality of life and prognosis. Poor management of this type of pain owing to the lack of full understanding undermines patients’ physical and mental quality of life, which often results in a grim prognosis, such as depression, myocardial infarction, lower limb amputation, and even mortality. In the present article, we review the current strategy in the pain management of diabetes-related CLTI. The endovascular therapy, pharmacological therapies, and other optional methods could be selected following comprehensive assessments to mitigate ischemic-related pain, in line with our current clinical practice. It is very important for clinicians and patients to strengthen the understanding and build intervention strategy in ischemic pain management and possible adverse consequence.
Sabot Discard Characteristics under Different Spin Rates of the Rifled Barrel Launching APFSDS
Authors: Zhang Chengqing , Wang Huiyuan , Liu Ting , Duo Yingxian
Published: May 2021

The sabot discard asymmetry caused by spinning affects the exterior ballistic characteristics and shooting accuracy of a gun with the rifled barrel. To gain a deeper understanding of the complex sabot discard performance for the armor‐piercing, fin‐stabilized discarding sabot (APFSDS), a numerical investigation is performed to assess the effects of the spin rate on the sabot discard characteristics. We obtain the calculation boundary by the interior ballistics and the firing conditions and carry out a numerical simulation under different spin rates using computational fluid dynamics (CFD) and a dynamic mesh technique. We analyze four aspects of sabot discard characteristics, namely, sabot separation, rod surface pressure, rod aerodynamic parameters, and discarding quantization parameters. Computational results show that the sabot separation nearly presents perfect symmetry at 0 rad/s, and when the initial rate of the sabot increases, there is more obvious separation asymmetry, and it contributes to the relative position variation among the sabots and the rod. The distinction of rod surface pressure indicates that the choked flow is the strongest flow source, and the spin rate has almost no effect on the pressure of the rod front part. When the monitoring point moves towards the fins, the pressure distribution and intensity change more dramatically. The initial spin rate and separation asymmetry produce a variation in the surface pressure, which further influences the rod aerodynamic characteristics. The discarding quantization parameters exhibit a certain variation rule with its spin rate. 2,000 rad/s has a significant influence on the rod aerodynamic coefficients during the weak coupling phase. When the spin rate is in the range of 0–900 rad/s, the discarding characteristics remain the same. However, when the spin rate exceeds 900 rad/s, the separation time and aerodynamic impulse have a quadratic polynomial relationship with the rate. Additionally, a spin rate of 1,000 rad/s is the optimal value for a rifled barrel gun.
Magnitude and Determinants of Dental Anxiety among Adult Patients Attending Public Dental Clinics in Dar-Es-Salaam, Tanzania
Authors: Musalam Kauther , Sohal Karpal S. , Owibingire Sira S. , Kileo Baraka
Published: May 2021

Introduction. It is estimated that, about 40% of the population suffer from dental anxiety. Dental anxiety is considered to be complex and multifactorial with a wide range of provoking factors which may be patient, provider, or environment-related. Aim. This study aimed to assess the magnitude and determinants of dental anxiety among adult patients attending public dental clinics in Dar es Salaam, Tanzania. Methodology. This was a descriptive cross-sectional study carried out in 4 public hospitals in Dar es Salaam, Tanzania. It included 300 adult patients who had dental caries, periodontal diseases, or dental trauma. Data were collected using a self-administered Modified Dental Anxiety Scale (MDAS) questionnaire. Data were analyzed using the SPSS computer software version 23. A one-way Analysis of Variance (ANOVA) was used to assess the association between variables, and the significance level was set atp<0.05. Results. The mean age of participants was 32.18 years (±11.06 SD) with a male-to-female ratio of 1 : 1.43. The means MDAS score was 12.84 ± 4.99. Tooth extraction had the highest mean MDAS score. The majority (261, 87%) of participants had mild-to-severe anxiety. The most common (72.2%) anxiety-provoking factor was an unsympathetic dentist; others included unawareness of the procedure to be carried out (58.3%) and the presence of apprehensive patients (52.0%). The level of anxiety was found to be statistically significantly associated (p<0.05) with young age [p=0.009, AOR 3.06 (95% CI, 1.32, 7.09), female patients [p<0.001, AOR 4.45 (95% CI, 2.05, 9.70)], and a higher education level [p<0.05, AOR 2.32 (95% CI, 1.03, 5.25)]. Conclusion. The prevalence of dental anxiety was high among the participants of this study. Female gender, young age, and a higher level of education constituted determinants of dental anxiety. An unsympathetic practitioner, unawareness of the procedure, and presence of apprehensive patients were the common anxiety-provoking factors.
Male Circumcision Reduces Penile HPV Incidence and Persistence: A Randomized Controlled Trial in Kenya
Authors: Smith Jennifer S. , Backes Danielle M. , Hudgens Michael G. , Mei Wenwen , Chakraborty Hrishikesh , Rohner Eliane , Moses Stephen , Agot Kawango , Meijer Chris J.L.M. , Bailey Robert C.
Published: May 2021

Background:

Male circumcision reduces the risk of human immunodeficiency virus infection in men. We assessed the effect of male circumcision on the incidence and natural history of human papillomavirus (HPV) in a randomized clinical trial in Kisumu, Kenya.

Methods:

Sexually active, 18- to 24-year-old men provided penile exfoliated cells for HPV DNA testing every 6 months for 2 years. HPV DNA was detected via GP5+/6+ PCR in glans/coronal sulcus and in shaft samples. HPV incidence and persistence were assessed by intent-to-treat analyses.

Results:

A total of 2,193 men participated (1,096 randomized to circumcision; 1,097 controls). HPV prevalence was 50% at baseline for both groups and dropped to 23.7% at 24 months in the circumcision group, and 41.0% in control group. Incident infection of any HPV type over 24 months was lower among men in the circumcision group than in the control group [HR = 0.61; 95% confidence interval (CI), 0.52–0.72]. Clearance rate of any HPV infection over 24 months was higher in the circumcision group than in the control group (HR = 1.87; 95% CI, 1.49–2.34). Lower HPV point-prevalence, lower HPV incidence, and higher HPV clearance in the circumcision group were observed in glans but not in shaft samples.

Conclusion:

Male circumcision reduced the risk of HPV acquisition and reinfection, and increased HPV clearance in the glans.

Impact:

Providing voluntary, safe, and affordable male circumcision should help reduce HPV infections in men, and consequently, HPV-associated disease in their partners.
Achieving Quiescence with Fluocinolone Implants
Authors: McGregor Freia , Dick Andrew D. , Burke Tomas
Published: May 2021

Persistent anterior uveitis causing cystoid macular oedema may necessitate either intraocular or systemic immunosuppression. This case report highlights how a newly licenced treatment, fluocinolone acetonide (Iluvien®, Alimera Sciences Ltd., England, UK) achieves quiescence in refractory and steroid-dependent disease and in the presence of an acute relapse.
Eccrine Porocarcinoma: A Challenging Diagnostic and Therapeutic Tumoral Entity
Authors: Le Ha Mo Linh , Faugeras Laurence , De Moor Véronique , Fervaille Caroline , Vander Borght Thierry , Collette Fanny , D’Hondt Lionel
Published: May 2021

Eccrine porocarcinoma is a rare malignant cutaneous tumor with high rates of extracutaneous spread, and its diagnosis and management can be quite challenging. This is a case of an 82-year-old woman presenting with an asymptomatic and chronic pubic skin lesion for whom the work-up required many investigations and procedures to confirm the diagnosis of metastatic eccrine porocarcinoma. Indeed, the patient underwent a wide local excision of the skin lesion, imaging with an FDG-PET scan, a colonoscopy, and two inguinal node dissections. As illustrated in this case, surgery should always be considered to achieve disease remission. Other treatments such as chemotherapy and radiotherapy have also been reported in the literature without clear standard guidelines.
FISH Identifies Chromosome Differentiation Between Contemporary Genomes of Wild Types and the Ancestral Genome of Unisexual Clones of Dojo Loach, Misgurnus anguillicaudatus
Authors: Kuroda Masamichi , Shibata Kiko , Fujimoto Takafumi , Murakami Masaru , Yamaha Etsuro , Arai Katsutoshi
Published: May 2021

In dojo loach (Misgurnus anguillicaudatus), although most wild types are gonochoristic diploids that are genetically differentiated into 2 groups, A and B, clonal lineages appear in certain localities. Clonal loaches have been considered to have hybrid origins between the 2 groups by a series of genetic studies. In this study, using FISH with a newly developed probe (ManDra-A), we identified 26 (1 pair of metacentric and 12 pairs of telocentric chromosomes) of 50 diploid chromosomes in contemporary wild-type group A loach. In contrast, ManDra-A signals were not detected on metacentric chromosomes derived from the ancestral group A of clonal loach. The FISH results clearly showed the presence of certain differentiations in metacentric chromosomes between ancestral and contemporary group A loach. Two-color FISH with ManDra-A and group B-specific ManDra (renamed ManDra-B) probes reconfirmed the hybrid origin of clones by identifying chromosomes from both groups A and B in metaphases. Our results showed the hybrid origin of clonally reproducing fish and the possibility that chromosomal differentiation between ancestral and contemporary fish can affect gametogenesis. In meiotic spermatocytes of sex-reversed clones, ManDra-A, and not ManDra-B, signals were detected in 12 out of 50 bivalents. Thus, the results further support the previous conclusion that clonal gametogenesis was assured by pairing between sister chromosomes duplicated from each ancestral chromosome from group A or B. Our study deepens the knowledge about the association between clonality and hybridity in unisexual vertebrates.
Acute Macular Neuroretinopathy in a Patient with Retinal Vascular Tortuosity
Authors: Karska-Basta Izabella , Pociej-Marciak Weronika , Romanowska-Dixon Bożena , Bukowska-Mikos Barbara
Published: May 2021

We report a rare case of a young woman with acute macular neuroretinopathy (AMN) in the right eye and concomitant retinal vascular tortuosity in both eyes. A 19-years-old woman presented with a sudden loss of central vision in the right eye. Apart from flu-like infection 2 weeks before the onset of symptoms, she reported overall good health. She used oral contraceptive pills. Multimodal imaging techniques including color fundus photography, fundus autofluorescence, infrared reflectance imaging, fluorescein angiography, swept-source optical coherence tomography (SS-OCT), and visual field assessment were used for the diagnosis of AMN as well as disease monitoring during follow-up. At presentation, ophthalmoscopy revealed a reddish parafoveal lesion, while SS-OCT showed hyper-reflectivity in the outer plexiform and outer nuclear layers with a slightly disrupted inner segment/outer segment junction. All these imaging findings indicated AMN, but the interpretation was slightly difficult due to the presence of tortuous retinal arteries in both eyes. During the disease course, functional and morphological recovery was documented at 1- and 6-month follow-up. However, as the abnormal appearance of the retinal vessels did not change, congenital retinal vascular tortuosity was diagnosed. Since the pathogenesis of AMN has not been fully elucidated, there is currently no effective treatment. Numerous studies have emphasized a vascular origin and the key role of ischemia in AMN. Our rare case suggests that congenital tortuosity of the retinal vessels, although constituting a common finding in healthy individuals, may be involved in the pathophysiology of the disease.
Digital Biomarkers of Cognitive Frailty: The Value of Detailed Gait Assessment Beyond Gait Speed
Authors: Zhou He , Park Catherine , Shahbazi Mohammad , York Michele K. , Kunik Mark E. , Naik Aanand D. , Najafi Bijan
Published: May 2021

Background: Cognitive frailty (CF), defined as the simultaneous presence of cognitive impairment and physical frailty, is a clinical symptom in early-stage dementia with promise in assessing the risk of dementia. The purpose of this study was to use wearables to determine the most sensitive digital gait biomarkers to identify CF. Methods: Of 121 older adults (age = 78.9 ± 8.2 years, body mass index = 26.6 ± 5.5 kg/m2) who were evaluated with a comprehensive neurological exam and the Fried frailty criteria, 41 participants (34%) were identified with CF and 80 participants (66%) were identified without CF. Gait performance of participants was assessed under single task (walking without cognitive distraction) and dual task (walking while counting backward from a random number) using a validated wearable platform. Participants walked at habitual speed over a distance of 10 m. A validated algorithm was used to determine steady-state walking. Gait parameters of interest include steady-state gait speed, stride length, gait cycle time, double support, and gait unsteadiness. In addition, speed and stride length were normalized by height. Results: Our results suggest that compared to the group without CF, the CF group had deteriorated gait performances in both single-task and dual-task walking (Cohen’s effect size d = 0.42–0.97, p < 0.050). The largest effect size was observed in normalized dual-task gait speed (d = 0.97, p < 0.001). The use of dual-task gait speed improved the area under the curve (AUC) to distinguish CF cases to 0.76 from 0.73 observed for the single-task gait speed. Adding both single-task and dual-task gait speeds did not noticeably change AUC. However, when additional gait parameters such as gait unsteadiness, stride length, and double support were included in the model, AUC was improved to 0.87. Conclusions: This study suggests that gait performances measured by wearable sensors are potential digital biomarkers of CF among older adults. Dual-task gait and other detailed gait metrics provide value for identifying CF above gait speed alone. Future studies need to examine the potential benefits of gait performances for early diagnosis of CF and/or tracking its severity over time.
Patient Experiences of Postinfectious Olfactory Dysfunction
Authors: Philpott Carl M , Boardman James , Boak Duncan
Published: May 2021

Introduction: To highlight the importance of the need for new treatment modalities, this study aimed to characterise the experience of patients with postinfectious olfactory dysfunction (PIOD) in terms of the treatment they received. Methods: An online survey was hosted by the Norwich Clinical Trials Unit on the secure REDCap server. Members of the charity Fifth Sense (the UK charity that represents and supports people affected by smell and taste disorders) were invited to participate. Results: There were 149 respondents, of whom 127 had identified themselves as having (or had) PIOD. The age range of respondents to the survey was 28–85 years, with a mean of 58 ± 12 years, with the duration of their disorder <5 years in 63% of cases. Respondents reported experiencing variable treatment with oral and/or intranasal steroids given typically (28%), often with no benefit, but with 50% receiving no treatment whatsoever; only 3% reported undertaking olfactory training. Over two-thirds of patients experience parosmia and, up to 5 years from the onset of the problem, were still actively seeking a solution. Conclusion: There appears to be a need to encourage greater use of guidelines for olfactory disorders amongst medical practitioners and also to develop more effective treatments for patients with PIOD, where there is clearly an unmet need.
Quality Control in the Slovenian National Colorectal Cancer Screening Program
Authors: Tepes Bojan , Stefanovic Milan , Stabuc Borut , Mlakar Dominika Novak , Grazio Snjezana Frkovic , Zakotnik Jozica Maucec
Published: May 2021

Objectives: The objective of the study was to assess the impact of an internal quality indicator (QI) audit on the quality level of colonoscopies in the National Colorectal Cancer Screening Program (NCCSP). Design: Sixty-eight colonoscopists from 29 endoscopic centres participated in the NCCSP from April 2009 to January 2015. Controlled QIs were the percentage of total colonoscopies, adenoma detection rate (ADR), mean adenoma per procedure (MAP), mean adenoma per positive procedure (MAP+), right-sided ADR, sessile serrated lesion (SSL) detection rate, and patient responses to post-procedural questionnaires. A group of 3 expert endoscopists from the NCCSP Council performed 91 inspections and provided education. Results: A total of 891.364 (58.2%) Slovenian citizens participated in the first 3 screening rounds of the NCCSP. Among 46.552 (6%) positive individuals, 42.866 (92.1%) underwent first colonoscopies. Total colonoscopies were performed in 98% of endoscopies (p = 0.459 between cycles), mean ADR was 51.8% (p = 0.872 between cycles), mean percentage of adenoma in the right colon was 37.5% (p = 0.227 between cycles), mean MAP was 1.1 (p = 0.981 between cycles), mean MAP+ was 2.0 (p = 0.824 between cycles), and mean SSL detection rate was 3% (p < 0.001). We observed great difference in QIs between endoscopists and a significant increase in MAP, ADR in the right colon, and SSL per endoscopist during the 6-year period. Due to quality underperformance, 3 endoscopic centres (10.3%) and 13 endoscopists (19.1%) were excluded from the program. Conclusions: The success of the NCCSP is related to the quality of colonoscopies performed. To ensure the proper quality level, regular audit and permanent education are needed.
Diarrhea as a Clinical Challenge: General Practitioner Approach
Authors: Sokic-Milutinovic Aleksandra , Pavlovic-Markovic Aleksandra , Tomasevic Ratko S. , Lukic Snezana
Published: May 2021

Background: Diarrhea is defined as the passage of loose stools and increase in stool frequency, weight, or volume. Diarrhea is an important health issue since it accounts for 2.5 million deaths in the world each year. Summary: Diarrhea can be acute, persistent, or chronic. Acute diarrhea (AD) is usually infectious, caused by viruses, less frequently by bacteria and parasites. The majority of cases of AD are self-limiting and do not require diagnostic workup. The use of diagnostic tests in AD should be limited to patients with signs of severe dehydration, bloody stools, persistent fever and those suffering from immunodeficiencies using immunosuppressive therapy or to cases of suspected nosocomial infection. These patients should be referred to gastroenterologists or infectious disease specialists. Therapy in AD consists of early oral refeeding, antidiarrheal medications, antibiotics, and probiotics. Chronic diarrhea (CD) has diverse etiology. The majority of patients have self-limiting symptoms or functional gastrointestinal disorders. Patients with blood in stool, weight loss, clinical and laboratory signs of anemia, and palpable mass in the abdomen (red flag symptoms) need urgent gastroenterology referral. Therapy in CD is possible when the underlying cause of symptoms is identified. Key Messages: The general practitioner should identify high-risk patients with AD and/or red flag symptoms for urgent gastroenterology referral.
Abstract 12535: MicroRNA-663 Ameliorates Monocrotaline-induced Pulmonary Arterial Hypertension by Targeting TGFβ1/smad2/3 Signaling
Authors: Zhu Ni , Li Pan , Du He , Qin Yongwen , Zhao Xianxian
Published: May 2021

Objective:
Pulmonary vascular remodeling due to excessive growth factor production and pulmonary artery smooth muscle cells (PASMCs) proliferation is the hallmark feature of pulmonary arterial hypertension (PAH). Recent studies suggest that miR-663 is a potent modulator for tumorigenesis and atherosclerosis. However, whether miR-663 involves in pulmonary vascular remodeling is still unclear.

Methods and Results:
By using quantitative RT-PCR, we found that miR-663 was highly expressed in normal human PASMCs. In contrast, circulating level of miR-663 dramatically reduced in PAH patients. In addition, in situ hybridization showed that expression of miR-663 was decreased in PAMSCs of PAH patients. Furthermore, MTT and cell scratch-wound assay showed that transfection of miR-663 mimics significantly inhibited platelet derived growth factor (PDGF)-induced PASMC proliferation and migration, while knockdown of miR-663 expression enhanced these effects. Mechanistically, dual-luciferase reporter assay revealed that miR-663 directly targets the 3’UTR of TGF-β1. Moreover, western blots and ELISA results showed that miR-663 decreased PDGF-induced TGF-β1 expression and secretion, which in turn suppressed the downstream smad2/3 phosphorylation and collagen I expression. Finally, intratracheal instillation of adeno-miR-663 dramatically attenuated pulmonary vascular remodeling and right ventricular hypertrophy, as well as right ventricular systolic pressure and mean pulmonary arterial pressure in MCT-induced PAH rat models.

Conclusion:
These results indicate that miR-663 is a potential biomarker for PAH. MiR-663 decreases PDGF-BB-induced PAMSCs proliferation and ameliorates pulmonary vascular remodeling and right ventricular hypertrophy in MCT-PAH by targeting TGF-β1/smad2/3 signaling. These findings suggest that miR-663 may represent as an attractive approach for the diagnosis and treatment of PAH.
Abstract 12575: Feasibility of Management in General Ward Settings for Hemodynamic Stable Patients With Acute Myocardial Infarction
Authors: Tateishi Kazuya , Kitahara Hideki , Saito Yuichi , Nakagomi Atsushi , Kuwabara Hiroyo , Inoue Takahiro , Kobayashi Yoshio
Published: May 2021

Background:
Although admission to the coronary care unit (CCU) is strongly recommended for ST-segment elevation myocardial infarction (STEMI) patients receiving primary percutaneous coronary intervention (PPCI) by current guidelines, it remains unclear whether it is suitable for hemodynamically stable patients with acute myocardial infarction (AMI). The aim of this study was to evaluate the safety of management in the general ward (GW) in hemodynamically stable AMI patients after PPCI compared to the CCU.

Methods:
Using a large nationwide administrative database, a cohort of 19,426 patients who were diagnosed as AMI in 52 hospitals, which were capable of admission to CCU, between Jan 2015 and Dec 2019, was retrospectively analyzed. Patients with mechanical circulatory support and Killip classification 4, and without PPCI, on the day of admission were excluded. Consequently, 5,736 patients were divided into the CCU group (n=3,488) and the GW group (n=2,248) based on the type of hospitalization room on admission after PPCI. A propensity score-matched (PSM) analysis was performed between the 2 groups, and 1,690 pairs of patients were matched.

Results:
The CCU group showed a higher prevalence of Killip classification 3 and ambulance use compared to the GW group. In the PSM model, Kaplan-Meier curve analysis showed there was no significant difference in the incidence of 30 days in-hospital mortality (Log rank p=0.48). On the other hand, total cost of hospitalization was lower in the GW group. Multivariable analysis did not show the association of GW admission with 30 days in-hospital mortality (HR: 1.07, 95% CI: 0.63-1.82, p=0.795).

Conclusions:
Management in the GW was not associated with 30 days in-hospital mortality for hemodynamically stable AMI patients after PPCI compared to the CCU, whereas it reduced the total cost of hospitalization. It may be feasible for hemodynamically stable AMI patients to be admitted directly to the GW after PPCI.
Abstract 12586: Assessing Valvuloarterial Impedance in Aortic Stenosis: A Comparison of Echocardiographic- and Cardiac Magnetic Resonance-derived Methods
Authors: Hungerford Sara L , Adji Audrey , Bart Nicole K , Lin Linda , Jabbour Andrew , Hayward Christopher S , Muller David W , Gorrie Natasha
Published: May 2021

Introduction:
Valvuloarterial impedance (Z
VA
) represents the valvular and arterial factors that oppose Left Ventricular (LV) ejection and is recognised as an important index to assess global LV load in patients with Aortic Stenosis (AS). Z
VA
is traditionally determined by Transthoracic Echocardiogram (TTE) and brachial cuff pressure.

Hypothesis:
Our study sought to compare Z
VA-TTE
with Z
VA
calculated using a simultaneous Cardiac Magnetic Resonance (CMR) and Applanation Tonometry (AT) (Z
VA-CMR
) technique to determine whether TTE measurement of aortic flow velocity resulted in an underestimation of Z
VA.

Methods:
Twenty AS patients underwent a protocol of CMR/AT followed by TTE. Z
VA-CMR
was determined as the relationship of derived aortic pressure (radial) to CMR aortic flow velocity in the frequency domain. Z
VA-TTE
was determined from digitised flow velocity within the left ventricular outflow tract (LVOT) on pulsed-wave Doppler and derived central pressure waveforms. Systemic vascular resistance (SVR) was calculated from mean pressure and flow. Values from both methods were compared.

Results:
Our study found that Z
VA-TTE
values (mean±SD, 638±381 dyne.s.cm
-3
) were consistently lower (p=0.07) than Z
VA-CMR
values (946±318 dyne.s.cm
-3
), and attribute this to an overestimation of LVOT flow velocity on TTE. SVR calculated by CMR/AT (2215±616 dyne.s.cm
-5
) was almost four times higher than TTE (618±245 dyne.s.cm
-5
) (p<0.001). This is due to more robust axi-symmetrical sampling of aortic flow across the entire cross-section of the ascending aorta (well above the stenotic jet) during CMR, than using operator-dependent TTE.

Conclusions:
Whilst Z
VA -TTE
is commonly performed in patients with AS to assess global LV load, newer methods to assess Z
VA
using simultaneous CMR/AT likely represent a more accurate non-invasive assessment.
Abstract 12598: Stress Testing During Long-term Follow-up After Kawasaki Disease
Authors: Dionne Audrey , Beattie Meaghan , Giorgio Thomas , Baker Annette L , Chen Ming Hui , Shafer Keri M , Powell Andrew J , de Ferranti Sarah , Fulton David R , Newburger Jane W , FRIEDMAN Kevin G
Published: May 2021

Introduction:
The American Heart Association (AHA) guidelines recommend testing for inducible myocardial ischemia in all patients with a history of coronary artery aneurysm (CAA) after Kawasaki disease (KD). Because the prevalence of clinical coronary complications is exceedingly low in patients whose worst-ever CAA dimension was <large/giant, we examined the yield of stress testing in KD over a 20-year period.

Methods:
Retrospective study including patients <18 yo with KD who underwent cardiac imaging to evaluate for inducible ischemia between 2000-2019. Patients with a prior coronary artery intervention were excluded. Inducible ischemia was defined as stress-induced reversible wall motion abnormalities on echocardiogram or cardiac MRI, or reversible defect on nuclear myocardial perfusion imaging.

Results:
A total of 588 stress tests were performed in 208 patients at median age of 12.4 [IQR 8.8, 16.8] years, 8.3 [IQR 5.0, 12.9] years after diagnosis (Table). Tests were performed using either exercise stress (545 [93%] tests) or pharmacologic stress with dobutamine (43 [7%] tests). Echocardiography was the most frequently used modality (n=481, 82%), followed by nuclear imaging (n=133, 23%) and cardiac MRI (n=53, 9%). Inducible ischemia was found on 11 (2%) tests in 6 (3%) patients. All patients with inducible ischemia had a history of giant CAA with persistent CAA at time of testing (moderate CAA in 2 (18%) tests, giant CAA in 9 (82%) tests). After finding inducible ischemia on stress test, coronary artery bypass grafting was performed in 3 cases, cardiac catheterization in 4, stress testing using a different imaging modality in 1, and careful clinical monitoring without intervention in 3.

Conclusions:
Inducible ischemia was found in 2% of test after KD, and only in patients with a history of giant CAA. Recommendations in the 2017 AHA guidelines for KD for testing for myocardial ischemia in patients with non-giant CAA should be reconsidered in light of these findings.
Abstract 12604: Effect of Psychotherapy on Quality of Life and Recurrence of Events in Patients With Recurrent Vasovagal Syncope: A Randomized Study
Authors: de Barros e Silva Renata , Hachul Denise , DE BARROS E SILVA PEDRO GABRIEL M , Scanavacca Mauricio I
Published: May 2021

Introduction:
Vasovagal syncope presents a benign prognosis in terms of survival but is associated with significant impairment on quality of life (QoL). Poor emotional status contributes to the recurrence of events.

Hypothesis:
Among patients with recurrent vasovagal syncope, weekly sessions of psychotherapy may improve QoL and reduce the number of events during one year of follow-up.

Methods:
A randomized controlled trial was conducted including 10 patients with recurrent vasovagal syncope and positive tilt test. Cardiac disease and ongoing psychotherapeutic interventions were the main exclusion criteria. After randomization, half of the eligible patients underwent weekly sessions of psychotherapy during 12 months, while the control group was followed according to the standard of care, without psychotherapy. QoL by SF-36 and recurrence of syncope and pre-syncope were compared between the 2 groups and also in each group pre and post randomization.

Results:
All patients had a positive tilt test (80% with mixed vasovagal response), 70% were female and the mean age was 47.4 ± 11.1 years. The average rate of events before inclusion was 4.1 (± 3.4) syncopes/year and 1.26 (± 0.5) episodes of presyncope/week. The groups were well balanced at baseline and all patients completed the planned follow-up of one year. In the assessment of QoL by SF-36, comparing before and one year after randomization, there was no statistically significant difference in the control group (49.9 ± 9.8 vs 46.9 ± 3.4, P = 0.20) but there was a significant improvement in the intervention group (44.9 ± 11.9 vs 68.8 ± 7.8, P < 0.01). Comparing both groups at 12 months, patients that underwent sessions of psychotherapy had better QoL (68.8 ± 7.8 vs 46.9 ± 3.4, P < 0.01). Regarding the recurrence of syncope events, there was no significant change in the control group; however, in the intervention group there was a significant reduction in the rate of presyncope episodes per month (5.6 ± 2.1 vs 1.7 ± 0.9; P = 0.02) and also a significant reduction in the rate of syncope per year (4.6 ± 3.3 vs 1.0 ± 0.7; P = 0.04).

Conclusions:
In a randomized clinical trial, patients with recurrent vasovagal syncope undergoing regular psychotherapeutic intervention had less recurrence of events and improved quality of life in one year.
Abstract 12613: Patient-reported Outcomes in a Multidisciplinary Electrophysiology-psychology Ventricular Arrhythmia Clinic
Authors: Nguyen Andrew , Dornblaser John , Gray Andrew , Paladino Karen , Kovacs Adrienne , Nazer Babak
Published: May 2021

Background:
Ventricular arrhythmias (VAs) and their treatment have been associated with psychological distress and poorer quality of life (QOL) in research studies. Patient-reported outcome (PRO) measures are beginning to be introduced in clinical settings and early experiences with their clinical utility warrant attention. We wanted to describe PROs of patients attending a multidisciplinary VA clinic in order to elucidate roles that PRO measures might have in clinical settings.

Methods:
In this retrospective study, we enrolled patients with history of sustained VA and/or ICD shock at their initial visit to a clinic staffed by an electrophysiologist and a psychologist. Patients completed several PRO measures including the following: anxiety and depression symptoms, visual analog scales for health status and QOL, cardiac device acceptance, ICD shock anxiety, and general cardiac anxiety. Here we report total scores for general PROs and item-level analysis of the three cardiac-specific measures.

Results:
A total of 57 patients (56 ±15 years; 84% male) were included; 39% had a history of sudden cardiac arrest, 70% had prior ICD shock and 44% had previously undergone VA ablation. Symptoms that exceeded clinical thresholds were common for anxiety (49%) and depression (20%). On 0-100 visual analogue scales, the mean rating for health status was 57 ± 16 and for QOL was 66 ± 18. Item-level analysis of cardiac-specific PROs revealed that between 40% and 50% of patients endorsed specific concerns regarding return to work, resumption of physical activities, and sexual relations (Table 1).

Conclusion:
Among patients attending a VA clinic, elevated symptoms of anxiety and depression were common and self-reported health status and QOL were low. Although PRO total scores provided general information, review at the individual item level provided critical information about potential sources of anxiety that can guide cardiologists during discussions with patients.
Abstract 12633: Use of Nicorandil is Associated With Increased Risk of Incident Atrial Fibrillation- A Population-based Nested Case-control Study and Molecular Studies to Explain the Association
Authors: Huang Pang-shuo , Lee Chien-Chang , Chan Chia-Ying , Rumery Kyle , Su Ke-Ying , Hsu Tze-Chun , Tsai Chia-Ti
Published: May 2021

Background:
Nicorandil is a potent vasodilator of coronary vessels through its effect on opening of ATP-sensitive potassium channel (KATP), and has been used as an antianginal agent. Activation of potassium channels play an important role in the mechanism of atrial fibrillation (AF) or atrial flutter (AFL). Accordingly, whether use of nicorandil might contribute to initiation and/or perpetuation of AF/AFL remained unknown.

Objectives:
To determine the relationship between use of nicorandil and risk of atrial fibrillation.

Methods:
We performed a nested case-control study using a cohort of 1 million people assembled from the National Health Insurance Research Database (NHIRD) of Taiwan. The association between nicorandil use and risk of atrial fibrillation was estimated by logistic regression model. We also performed molecular and cellular studies to explain the association.

Results:
A total of 715 individuals who experienced atrial fibrillation or atrial flutter were matched to 72,215 controls. To account for the potential unmeasured confounders, we identified nitrate users in the same cohort as an active comparator. After adjustment, new use of nicorandil was found to be associated with increased risk for atrial fibrillation or atrial flutter (odds ratio [OR], 2.34; 95% CI 1.07-5.13) compared to nitrate use. Activation of potassium channel shortens atrial action potential duration (APD), which subsequently perpetuates AF. Dysfunction of mutated sarcKATP channels in atrial cells may lead to electrical instability and atrial fibrillation. We found expression of KATP in human atrial tissues. Furthermore, nicorandil directly shortened APD and the QT interval of cultured induced pluripotent stem cell (iPSC) derived cardiomyocytes (iPSC-CMs).

Conclusion:
Use of nicorandil, especially new use, was found to be associated with increased risk of AF or AFL. We also first showed the expression of KATP in human atria and use of nicorandil may promote or increase the risk of AF through activation of KATP and shortening of atrial APD.
Abstract 12638: Autophagy-mitophagy Induction Improves Cardiovascular Inflammation in a Murine Model of Kawasaki Disease Vasculitis
Authors: Marek-iannucci Stefanie , Gomez Angela , Moreira Debbie , Lane Malcolm , Porritt Rebecca , Lee Youngho , Shimada Kenichi , Crother Timothy R , Noval Rivas Magali , Arditi Moshe
Published: May 2021

Kawasaki Disease (KD), an acute febrile illness and systemic vasculitis of unknown etiology, is the leading cause of acquired heart disease among children. Recent experimental data from mouse models, as well as clinical, genetic and transcriptome evidence from KD patients suggest a key role of the NLRP3-IL-1β pathway in the pathogenesis of KD. NLRP3 can be activated by mitochondrial (mt) DNA released in the setting of defective autophagy/mitophagy, but a potential role for autophagy/mitophagy in KD cardiovascular inflammation has not been determined. In the
Lactobacillus casei
cell wall extract (LCWE) mouse model of KD vasculitis, LCWE injection in WT mice results in coronary arteritis, aortitis and myocarditis, mimicking human KD. We found that expression of the autophagy/mitophagy markers Parkin and p62 was significantly higher in whole lysate and mitochondrial fractions of heart tissue of LCWE-injected mice than controls, indicating impaired autophagic flux and mitophagy.

Parkin
-/-

mice developed significantly more LCWE-induced cardiovascular lesions than control mice, and treatment of WT mice with a GLP-1 receptor agonist, known to activate Parkin, significantly reduced LCWE-induced inflammation. LCWE-induced cardiovascular lesions were amplified in mice deficient in OGG1, a base excision repair protein sensitive to mtDNA damage. Finally, inhibiting autophagy with chloroquine exacerbated LCWE-induced KD vasculitis, whereas inducing autophagy by intermittent fasting decreased cardiovascular inflammation in the model. Altogether, our data suggest that impaired autophagy/mitophagy exacerbates KD and supports a role for mtDNA damage in the disease. These findings enhance our understanding of KD pathogenesis and may provide novel therapeutic targets.
Abstract 12640: Energy Drinks Prolong Early Repolarization (J-T
Peak
) Phase in a Healthy Population
Authors: Kaplan Samuel R , Syed Ghufran , Kozik Teri
Published: May 2021

Introduction:
Energy drinks continue to be the fastest growing beverage market with sales expected to reach $60 billion in the next few years, yet have demonstrated adverse cardiovascular effects such as prolongation of the QTc interval on EKG. While QTc prolongation observed with certain drugs has long been used as an indicator of increased risk of torsade de pointes, recent data has identified the early repolarization interval J-T
peak
(JTp) as a more specific marker for proarrhythmic potential. Drugs that selectively block the human ether-a-go-go related (hERG) potassium ion channel prolong QTc by prolonging both early repolarization (JTp) and late repolarization (T
peak
-T
end
[Tpe] interval), and are associated with an increased risk of torsade. In contrast, drugs that additionally block inward late sodium and L-type calcium prolong QTc by prolonging Tpe but not JTp, and have demonstrated reduced risk of torsade. In 2018, the C-Energy-X study demonstrated QTc prolongation in 22 healthy subjects (mean age 28 ± 7yrs) who consumed energy drink while at rest and following short periods of exercise. Our study provides a secondary analysis of this data in terms of its effect on JTp, a potentially more specific marker for torsade risk.

Methods:
Using H-Scribe software, two evaluators independently measured JTp and RR intervals from C-Energy-X subjects pre- and post-energy drink consumption in the rest and exercise phases. Values were corrected for heart rate using the linear correction formula JTpc=JTp + 0.150(1-RR), where RR is R-to-R interval. Mean JTpc values from each phase were analyzed using a paired sample two-tailed
t
-test.

Results:
In the resting phase following energy drink consumption (PCr), there was a statistically significant increase in JTpc intervals for 77% of subjects by a mean of 10.5ms (baseline=234 ± 21.3ms; PCr=245 ± 22.0ms;
p
=0.015). In the exercise phase following energy drink consumption (PCe), 64% of subjects increased JTpc intervals by a mean of 0.8ms which was not significant (baseline=225 ± 15.7ms; PCe=226 ± 17.9ms;
p
=0.845).

Conclusion:
In the resting phase, energy drink consumption was associated with statistically significant prolongation of JTpc, suggesting a theoretical increased risk of torsade de pointes.
Abstract 12677: Impaired Cardiomyocyte Contractility to Angiotensin-(1-12) in a Humanized Angiotensinogen Model of Hypertension
Authors: Liu Yixi , Cheng Heng Jie , Sun Xiaoqiang , Cao Jing , Chen Zhe , VonCannon Jessica L , Ahmad Sarfaraz , Ferrario Carlos M , Cheng Che
Published: May 2021

Background:
Angiotensin-(1-12) [Ang-(1-12)] is a chymase-dependent source for Angiotensin II (Ang II) inotropic activity that may be impaired in a model of sustained hypertension with high cardiac Ang II content due to insertion of the human angiotensinogen (AGT) gene in the rat genome. Accordingly, we evaluated the effects of Ang-(1-12) and Ang II on myocyte contractility and [Ca
2+
]
i
regulation in 9 adult male transgenic rats expressing the human AGT gene [TGR(hAGT)L1623)] and 9 SD controls.

Methods:
We compared LV myocyte contraction, relaxation and [Ca
2+
]
i
transient ([Ca
2+
]
iT
) responses to Ang-(1-12) (4x10
-6
M) and Ang II (10
-6
M) in freshly isolated LV myocytes.

Results:
Myocyte contraction (dL/dt
max
, 109.6 vs 127.9 μm/s), relaxation (dR/dt
max
, 95.3 vs 107.5 μm/s) and [Ca
2+
]
iT
(0.15 vs 0.24) were depressed in TGR(hAGT)L1623 rats compared to SD controls. Moreover, cell contractile and [Ca
2+
]
iT
responses following exposure to Ang-(1-12) or Ang II were markedly blunted. In SD myocytes, versus baseline, Ang II or Ang-(1-12) superfusion produced significant increases in dL/dt
max
[Ang II: 44% vs Ang-(1-12): 34%], dR/dt
max
(33% vs 26%) and [Ca
2+
]
iT
(31% vs 25%). Importantly, the magnitude of the responses to the two agents in TGR(hAGT)L1623 myocytes was significantly reduced. Versus the changes in SD myocytes, Ang-(1-12) caused significantly less increases in dL/dt
max
(22%), dR/dt
max
(16%) and [Ca
2+
]
iT
(15%) in TGR(hAGT)L1623 myocytes . Ang II also caused similar significantly attenuated increases in dL/dt
max
(27%), dR/dt
max
(25%) and [Ca
2+
]
iT
(23%). The Ang-(1-12)-induced inotropic effects were completely prevented in the presence of the inhibitory cAMP analog, Rp-cAMPS (10
–4
M, 2 hours) in both SD and TGR(hAGT)L1623 myocytes, but were further augmented only intransgenic rats after incubation of myocytes with the G
i
inhibitor, pertussis toxin (PTX, 2 μg/ml, 36°C, 5 hours).

Conclusions:
Ang-(1-12) stimulates LV myocyte contractile function and [Ca
2+
]
iT
in both SD and TGR(hAGT)L1623 rats. Furthermore, we now show that the blunted inotropic responses to Ang-(1-12) and Ang II in rats expressing the human AGT gene is mediated through a cAMP-dependent mechanism that is coupled to both stimulatory G and inhibitory PTX-sensitive G proteins.
Abstract 12678: Oral Anticoagulation Use in High Risk Atrial Fibrillation Patients is Much Higher Than Previously Reported
Authors: Ruzieh Mohammed , Naccarelli Gerald V , Wolbrette Deborah , Sendra-Ferrer Mauricio , Harskamp John v , Bentz Barbara , Caputo Gregory , McConkey Nathaniel , Mills Kevin , Wasemiller Stephen , Plamenac Jovan , Leslie Douglas , Glasser Frendy D , Abendroth Thomas W
Published: May 2021

Introduction:
Guidelines recommend oral anticoagulants (OAC) in high risk atrial fibrillation (HRAF) patients. It has been reported that >40% of such patients are not taking an OAC. We observed that active AF often was not present in patients labeled as having AF (either because of wrong diagnosis or no AF in last 5 years).

Hypothesis:
We undertook a systematic electronic medical record (EMR) review to determine the presence or absence of active AF to accurately identify HRAF patients requiring an OAC.

Methods:
We reviewed 6514 patients with presumed AF and 2 or more outpatient visits documented by at least one of: billing diagnosis, EMR encounter diagnosis, EMR problem list, or EKG interpretation.

Results:
Active AF was noted in 4555/6514 patients (69.7%) after 1959 patients with no prior history of AF or inactive AF were withdrawn from further analysis. In active AF patients, 3869 had HRAF with CHA
2
DS
2
-VASc ≥2. OAC use was statistically higher (p<0.0001 by McNamer’s test) in the active HRAF group [3090/3869 (79.9%) compared to the presumed HRAF group (62.9%)], Figure 1. There was no statistically significant difference in the use of OAC between men (80.7%) and women (78.8%), even in women with a CHA
2
DS
2
-VASc ≥3 (79.9%). In HRAF patients not taking an OAC (20.1%), expert review frequently disagreed with that recommendation suggesting that OACs can be taken in up to 92% of HRAF patients.

Conclusions:
1) Current registries with un-adjudicated EMR diagnoses over-report the number of HRAF patients not taking an OAC; 2) Expert adjudication of active AF diagnosis identifies a smaller OAC treatment gap than previously described; 3) absolute contraindication or repeated refusal to take an OAC exists in less than 10% of HRAF patients; and, 4) there were no gender differences in OAC use.