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BACKGROUND: Posttraumatic stress disorder (PTSD) has been associated with ischemic heart disease in women veterans, but evidence for associations with other cardiovascular disorders remains limited in this population. This retrospective longitudinal cohort study evaluated the association of PTSD with incident stroke/transient ischemic attack (TIA) in women veterans. METHODS AND RESULTS: Veterans Health Administration electronic health records were used to identify women veterans aged ≥18 years engaged with Veterans Health Administration health care from January 1, 2000 to December 31, 2019. We identified women veterans with and without PTSD without a history of stroke or TIA at start of follow-up. Propensity score matching was used to match groups on age, race or ethnicity, traditional cardiovascular risk factors, female-specific risk factors, a range of mental and physical health conditions, and number of prior health care visits. PTSD, stroke, TIA, and risk factors used in propensity score matching were based on diagnostic codes. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% CIs for associations of PTSD with an incident stroke/TIA composite. Subanalyses considered stroke and TIA separately, plus age- and race- or ethnicity-stratified analyses were carried out. The analytic sample included 208 092 women veterans (104 046 with and 104 046 without PTSD). PTSD was associated with a greater rate of developing stroke/TIA (HR, 1.33 [95% CI, 1.25-1.42], P

The current cardiac pacemakers are battery dependent, and the pacing leads are prone to introduce valve damage and infection, plus a complete pacemaker retrieval is needed for battery replacement. Despite the reported wireless bioelectronics to pace the epicardium, open-chest surgery (thoracotomy) is required to implant the device, and the procedure is invasive, requiring prolonged wound healing and health care burden. We hereby demonstrate a fully biocompatible wireless microelectronics with a self-assembled design that can be rolled into a lightweight microtubular pacemaker for intravascular implantation and pacing. The radio frequency was used to transfer energy to the microtubular pacemaker for electrical stimulation. We show that this pacemaker provides effective pacing to restore cardiac contraction from a nonbeating heart and have the capacity to perform overdrive pacing to augment blood circulation in an anesthetized pig model. Thus, this microtubular pacemaker paves the way for the minimally invasive implantation of leadless and battery-free microelectronics.

Background Although most individuals can adapt to a large iodine load and remain euthyroid, hypothyroidism can develop after iodine exposure. Hypothyroidism is associated with adverse cardiovascular consequences, including heart failure. This study was performed to investigate the relationships between iodine-induced hypothyroidism and incident heart failure. Methods and Results This cohort study of the US Veterans Health Administration (1998-2021) included adults aged ≥18 years with a serum thyroid-stimulating hormone (thyrotropin)

CONTEXT: Although iodine-induced hyperthyroidism is a potential consequence of iodinated radiologic contrast administration, its association with long-term cardiovascular outcomes has not been previously studied. OBJECTIVE: To investigate the relationships between hyperthyroidism observed after iodine contrast administration and incident atrial fibrillation/flutter. METHODS: Retrospective cohort study of the U.S. Veterans Health Administration (1998-2021) of patients age ≥18 years with a normal baseline serum thyrotropin (TSH) concentration, subsequent TSH

The lactoperoxidase (LPO)-hydrogen peroxide-halides reaction (LPO system) converts iodide and thiocyanate (SCN-) into hypoiodous acid (HOI) and hypothiocyanite (OSCN-), respectively. Since this system has been implicated in defense of the airways and oropharynx from microbial invasion, in this proof-of-concept study we measured the concentrations of these analytes in human saliva from a convenience clinical sample of 40 qualifying subjects before and after acute iodine administration via the iodinated contrast medium used in coronary angiography to test the hypothesis that an iodide load increases salivary iodide and HOI concentrations. Saliva was collected and salivary iodide, SCN-, HOI and OSCN- were measured using standard methodology. The large iodine load delivered by the angiographic dye, several 100-fold in excess of the U.S. Recommended Daily Allowance for iodine (150 µg/day), significantly increased salivary iodide and HOI levels compared with baseline levels, whereas there was no significant change in salivary SCN- and OSCN- levels. Iodine load and changes of salivary iodide and HOI levels were positively correlated, suggesting that higher iodide in the circulation increases iodide output and salivary HOI production. This first of its kind study suggests that a sufficient but safe iodide supplementation less than the Tolerable Upper Limit for iodine set by the U.S. Institute of Medicine (1,100 µg/day) may augment the generation of antimicrobial HOI by the salivary LPO system in concentrations sufficient to at least in theory protect the host against susceptible airborne microbial pathogens, including enveloped viruses such as coronaviruses and influenza viruses.

Electrical impedance spectroscopy (EIS) has been recognized to characterize oxidized low-density lipoprotein (oxLDL) in the metabolically active plaque. However, intravascular deployment of 3-D EIS-derived electrical impedance tomography (EIT) for endoluminal mapping of oxLDL-laden arterial walls remains an unmet clinical challenge. To this end, we designed the 6-point microelectrode arrays that were circumferentially configurated onto the balloon catheter for 15 intravascular EIS permutations. In parallel, we created the metabolically active plaques by performing partial ligation of right carotid artery in Yorkshire mini-pigs (n = 6 males), followed by demonstrating the plaque progression at baseline, 8 weeks, and 16 weeks of high-fat diet via computed tomography (CT) angiogram. Next, we deployed the 3-D EIS sensors to the right and left carotid arteries, and we demonstrated 3-D EIS mapping of metabolically active endolumen in the right but not left carotid arteries as evidenced by the positive E06 immunostaining for oxLDL-laden regions. By considering electrical conductivity (σ) and permittivity (ε) properties of collagen, lipid, and smooth muscle presence in the arterial wall, we further validated the 3-D EIS-derived EIT by reconstructing the histology of right and left carotid arteries for the finite element modeling of the oxLDL-laden endolumen, and we accurately predicted 3-D EIS mapping. Thus, we establish the capability of 3-D EIS-derived EIT to detect oxLDL-laden arterial walls with translational implication to predict metabolically active plaques prone to acute coronary syndromes or stroke.

BackgroundIodine and particularly its oxidated forms have long been recognized for its effective antiseptic properties. Limited in vitro and in vivo data suggest that iodine exposure may rapidly inactivate, reduce transmission, and reduce infectivity of SARS-CoV-2. We hypothesized that iodine exposure may be associated with decreased incident COVID-19 infection.MethodsA retrospective population-level cohort analysis was performed of the U.S. Veterans Health Administration between 1 March 2020 and 31 December 2020, before the widespread availability of vaccines against SARS-CoV-2. Multivariable logistic regression models estimated the adjusted odds ratios (OR) and 95% confidence intervals (CI) of the associations between iodinated contrast exposure and incident COVID-19 infection, adjusting for age, sex, race/ethnicity, place of residence, socioeconomic status, and insurance status.Results530,942 COVID-19 tests from 333,841 Veterans (mean ± SD age, 62.7 ± 15.2 years; 90.2% men; 61.9% non-Hispanic Whites) were analyzed, of whom 9% had received iodinated contrast ≤60 days of a COVID-19 test. Iodine exposure was associated with decreased incident COVID-19 test positivity (OR, 0.75 95% CI, 0.71-0.78). In stratified analyses, the associations between iodinated contrast use and decreased COVID-19 infection risk did not differ by age, sex, and race/ethnicity.ConclusionIodine exposure may be protective against incident COVID-19 infection. Weighed against the risks of supraphysiologic iodine intake, dietary, and supplemental iodine nutrition not to exceed its Tolerable Upper Limit may confer an antimicrobial benefit against SARS-CoV-2. A safe but antimicrobial level of iodine supplementation may be considered in susceptible individuals, particularly in geographic regions where effective COVID-19 vaccines are not yet readily available.

IntroductionBoth trauma exposure and post-traumatic stress disorder (PTSD) are associated with increased risk of cardiovascular disease (CVD), the leading cause of death in the USA. Endothelial dysfunction, a modifiable, early marker of CVD risk, may represent a physiological mechanism underlying this association. This mechanism-focused cohort study aims to investigate the relationship between PTSD (both in terms of diagnosis and underlying symptom dimensions) and endothelial dysfunction in a diverse, community-based sample of adult men and women.Methods and analysisUsing a cohort design, 160 trauma-exposed participants without a history of CVD are designated to the PTSD group (n=80) or trauma-exposed matched control group (n=80) after a baseline diagnostic interview assessment. Participants in the PTSD group have a current (past month) diagnosis of PTSD, whereas those in the control group have a history of trauma but no current or past psychiatric diagnoses. Endothelial dysfunction is assessed via flow-mediated vasodilation of the brachial artery and circulating levels of endothelial cell-derived microparticles. Two higher order symptom dimensions of PTSD-fear and dysphoria-are measured objectively with a fear conditioning paradigm and attention allocation task, respectively. Autonomic imbalance, inflammation, and oxidative stress are additionally assessed and will be examined as potential pathway variables linking PTSD and its dimensions with endothelial dysfunction. Participants are invited to return for a 2-year follow-up visit to reassess PTSD and its dimensions and endothelial dysfunction in order to investigate longitudinal associations.Ethics and disseminationThis study is conducted in compliance with the Helsinki Declaration and University of California, Los Angeles Institutional Review Board. The results of this study will be disseminated via articles in peer-reviewed journals and presentations at academic conferences and to community partners.Trial registration numberNCT03778307; pre-results.

IntroductionRandomized trials of new agents for HIV pre-exposure prophylaxis (PrEP) compare against emtricitabine and tenofovir disoproxil fumarate (F/TDF), without a placebo group. We used the well-characterized adherence-efficacy relationship for F/TDF to back-calculate the (non-PrEP) counterfactual background HIV incidence (bHIV) in a randomized trial of a novel PrEP agent and estimate comparative efficacy (to counterfactual bHIV).MethodsThe DISCOVER trial (ClinicalTrials.gov: NCT02842086) randomized 5387 men who have sex with men (MSM) and transgender women who have sex with men and demonstrated non-inferiority of emtricitabine and tenofovir alafenamide (F/TAF) to F/TDF (HIV incidence rate ratio [IRR] 0·47, 95% CI: 0·19 to 1.15). Tenofovir diphosphate (TFV-DP) levels in dried blood spots (DBS) were assessed for all diagnosed with HIV and in a random 10% of the cohort. We used a Bayesian model with a diffuse prior distribution, derived from established data relating tenofovir diphosphate levels to HIV prevention efficacy. This prior, combined with the F/TDF seroconversion rate and tenofovir diphosphate levels in DISCOVER, yielded Bayesian inferences on the counterfactual bHIV.ResultsThere were six versus 11 postbaseline HIV infections (0.14 vs. 0.25/100 person-years [PY]) on F/TAF and F/TDF respectively. Of the 11 on F/TDF, 10 had low, none had medium and one had high tenofovir diphosphate levels; among HIV-negative controls, 5% of the person-time years had low, 9% had medium and 86% had high TFV-DP levels. A non-informative prior distribution for counterfactual bHIV, combined with the prior for TFV-DP level-efficacy relationship, yielded a posterior counterfactual bHIV of 3·4 infections/100 PY (0.80 Bayesian credible interval [CrI] 1·9 to 5·9), which suggests a median HIV efficacy of 96% (0.95 CrI [88% to 99%]) for F/TAF and 93% (0.95 CrI [87% to 96%]) for F/TDF compared to bHIV.ConclusionsBased on the established connection of drug concentrations to PrEP prevention efficacy, a Bayesian framework can be used to estimate a synthetic non-PrEP control group in randomized, active-controlled PrEP trials that include a F/TDF-comparator group.

Background and purpose: There has not been a comprehensive study on the simultaneous effects of metformin, etoposide, and epirubicin on thyroid cancer cells. Hence, the current research proposed the in vitro study on the effect of metformin alone and in combination with etoposide and epirubicin on the rate of proliferation, apoptosis, necrosis, and migration against B-CPAP and SW-1736 cells as thyroid cancer cell lines. Experimental approach: MTT-based proliferation assay, combination index method, flow cytometry, and scratch wound healing assays were used to evaluate the simultaneous effects of the three approved drugs against thyroid cancer cells. Findings/Results: This study showed that the toxic concentration of metformin on normal Hu02 cells was more than 10 folds higher than B-CPAP and SW cancerous cells. Metformin in combination with epirubicin and etoposide could increase percentages of B-CPAP and SW cells in early and late apoptosis and necrosis phases in comparison with their single concentrations, significantly. Metformin in combination with epirubicin and etoposide could arrest the S phase in B-CPAP and SW cells, significantly. Metformin in combination with epirubicin and etoposide could reduce ~100% migration rate, whereas single concentrations of epirubicin and etoposide could reduce ~50% migration rate. Conclusion and implication: Combined treatment of metformin with anticancer drugs epirubicin and etoposide can increase the mortality in thyroid cancer cell lines and reduce the toxicity of these drugs on the normal cell line, which could be the starting point for proposing a new combination strategy in the therapy of thyroid cancer to induce more potency and reduce acute toxicity.

Ventricular arrhythmias originating from the papillary muscle of the ventricles are complex clinical problems. Catheter ablation has the potential to cure these arrhythmias. However, the procedure is usually challenging due to the specific anatomy, catheter instability and difficulty in localization of the origin of the arrhythmias. Intracardiac echocardiography (ICE) has been reported to be the suitable imaging method for assessing the location of focus in papillary muscles. We used transthoracic echocardiography (TTE), as a noninvasive cost-effective imaging supporting modality, in combination with 3D mapping to guide the exact localization and successful ablation of papillary muscle-originating premature ventricular contractions (PVCs). [ABSTRACT FROM AUTHOR]

ImportanceAdvances in perioperative cardiac management and an increase in the number of endovascular procedures have made significant contributions to patients and postoperative myocardial infarction (POMI) risk following high-risk vascular procedures. Whether these changes have translated into real-world improvements in POMI incidence remain unknown.ObjectiveTo examine the temporal trends of myocardial infarction (MI) following high-risk vascular procedures.Design, setting, and participantsA retrospective cohort study was performed using data collected from January 1, 2005, to December 31, 2013, in the American College of Surgeons National Surgery Quality Improvement Program database, to which participating hospitals across the United States report their preoperative, operative, and 30-day outcome data. A total of 90 303 adults who underwent a high-risk vascular procedure-open aortic surgery or infrainguinal bypass-during the study period were identified. Patients were divided into cohorts based on their year of operation, and their baseline cardiac risk factors and incidence of POMI were compared. Cases from 2005 to 2014 in the database were eligible for inclusion if one of their Current Procedural Terminology codes matched any of the operations identified as a high-risk vascular procedure. Data analysis took place from August 1, 2016, to November 15, 2016.ExposuresThe main exposure was the year of the operation. Other variables of interest included demographics, comorbidities, and other risk factors for MI.Main outcomes and measuresPrimary outcome of interest was the incidence of POMI.ResultsOf the 90 303 patients included in the study, 22 836 (25.3%) had undergone open aortic surgery and 67 467 (74.7%) had had infrainguinal bypass. The open aortic cohort comprised 16 391 men (71.9%), had a mean (SD) age of 69.1 (11.5) years, and was predominantly white (18 440 patients [80.8%] self-identified as white race/ethnicity). The infrainguinal bypass cohort included 41 845 men (62.1%), had a mean (SD) age of 66.7 (11.7) years, and had 51 043 patients (75.7%) who self-identified as white race/ethnicity. During the study period, patients who underwent open aortic procedures were more likely to be classified as American Society of Anesthesiologists class IV (7426 patients [32.6%] vs 15 683 [23.3%] for the infrainguinal bypass cohort) or class V (1131 [5.0%] vs 206 [0.3%]; P

This cohort study analyzes the cost and stabilization of disease in patients undergoing transcatheter and surgical aortic valve replacement.

Background: Iodinated contrast is commonly used for radiological procedures, with one dose delivering several hundred-fold the daily requirements needed for normal thyroid hormone production. Risks of excess iodine include incident thyroid dysfunction, which is associated with adverse cardiac outcomes, yet there are no prospective studies investigating the changes in cardiac physiology following iodine contrast administration. This study was conducted to investigate the longitudinal relationships between the amount of iodinated contrast administration and changes in cardiac electrophysiology and structure. Methods: A longitudinal cohort study was conducted with prospectively enrolled participants who received iodine contrast for elective computed tomography or coronary angiography. Serum thyroid function tests, electrocardiograms (EKG), and transthoracic echocardiograms were obtained serially until 36 months. Trends of electrical and structural cardiac changes following iodine contrast administration were assessed using mixed effect models. Results: The cohort was composed of 129 patients (median age, 70 [interquartile range: 63, 75] years; 98% male). Larger amounts of iodine exposure were associated with increases in QRS and QTc durations and decreased ejection fraction (EF), and these associations were still observed for follow-up EF after additionally adjusting for baseline values (the high-iodine contrast group vs. the low-iodine contrast group, −4.23% [confidence interval, −7.66% to −0.79%]). Dose–response analyses also showed lower EF with larger amounts of iodine received; these trends were not significant for the EKG parameters studied. Conclusions: Over a period of up to 36 months, a larger amount of administered iodine contrast was associated with lower EF among participants. Further investigation is needed to elucidate the long-term trends of electrical and structural cardiac function after iodine contrast administration. [ABSTRACT FROM AUTHOR]

Background: Management of atrial fibrillation (AF) in very severe obese patients is challenging. Cryoballoon ablation (CBA) represents an effective rhythm control strategy. However, data in this patient group were limited. Methods: Highly symptomatic AF patients with body mass index (BMI) ≥ 40 kg/m2 who had failed antiarrhythmic drug therapy and electrocardioversion and failure to achieve targeted body‐weight‐reduction underwent CBA. Results: Data of 72 very severe obese AF patients (Group A) and 129 AF patients with normal BMI (Group B, BMI < 25 kg/m2) were consecutively collected. Group A had significantly younger age (60.6 ± 10.4 vs. 69.2 ± 11.2 years), higher BMI (44.3 ± 4.3 vs. 22.5 ± 1.6 kg/m2). Procedural pulmonary vein isolation (PVI) was successful in all patients (2 touch‐up ablation in Group A). Compared to Group B, Group A had similar procedural (61.3 ± 22.6 vs. 57.5 ± 19 min), similar fluoroscopy time (10.1 ± 5.5 vs. 9.2 ± 4.8 min) but significantly higher radiation dose (2852 ± 2095 vs. 884 ± 732 µGym2). We observed similar rates of real‐time‐isolation (78.6% vs. 78.5%), single‐shot‐isolation (86.5% vs. 88.8%), but significantly longer time‐to‐sustained‐isolation (53.5 ± 33 vs. 43.2 ± 25 s). There was significantly higher rate of puncture‐site‐complication (6.9% vs. 1.6%) in Group A. One‐year clinical success in paroxysmal AF was (Group A: 69.4% vs. Group B: 80.2%; p <.001), in persistent AF was (Group A: 58.1% vs. Group B: 62.8%; p =.889). In Re‐Do procedures Group A had a numerically lower PVI durability (75.0% vs. 83.6%, p =.089). Conclusion: For very severe obese AF patients, CBA appears feasible, leads to relatively good clinical outcome. [ABSTRACT FROM AUTHOR]