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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<0.001). This elevated risk was especially pronounced in women <50 years old and in Hispanic/Latina women. CONCLUSIONS: Findings indicate a strong association of PTSD with incident stroke/TIA in women veterans. Research is needed to determine whether addressing PTSD and its downstream consequences can offset this risk.

OBJECTIVE We aimed to assess the effect of SGLT2i on arrhythmias by conducting a meta-analysis using data from randomized controlled trials(RCTs). BACKGROUND Sodium-glucose co-transporter 2 inhibitors (SGLT2i) have shown cardioprotective effects via multiple mechanisms that may also contribute to decrease arrhythmias risk. METHODS We searched in databases (PubMed, Embase, Cochrane Library, and clinicaltrials.gov) up to April 2023. RCTs comparing SGLT2i with placebo were included. The effects of SGLT2i on atrial fibrillation(AF), atrial flutter(AFL), composite AF/AFL, ventricular fibrillation(VF), ventricular tachycardia(VT), ventricular extrasystoles(VES), sudden cardiac death(SCD) and composite VF/VT/SCD were evaluated. RESULTS 33 placebo-controlled RCTs were included, comprising 88,098 patients (48,585 in SGLT2i vs. 39,513 in placebo). The mean age was 64.9 ± 9.4 years, 63.0% were male. The mean follow-up was 1.4 ± 1.1 years. The pooled-results showed that SGLT2i was associated with a significantly lower risk of AF [risk ratio(RR): 0.88, 95% confidence interval(CI) 0.78-1.00, P = 0.04] and composite AF/AFL (RR: 0.86, 95%CI 0.77-0.96, P = 0.01). This favorable effect appeared to be substantially pronounced in patients with HFrEF, male gender, dapagliflozin, and > 1 year follow-up. For SCD, only in heart failure patients, SGLT2i were found to be associated with a borderline lower risk of SCD (RR: 0.67, P = 0.05). No significant effects of SGLT2i on other ventricular arrhythmic outcomes were found. CONCLUSIONS SGLT2i lowers the risks of AF and AF/AFL, and this favorable effect appeared to be particularly pronounced in patients with HFrEF, male gender, dapagliflozin, and longer follow-up (> 1 year). SGLT2i lowers the risk of SCD only in heart failure patients.

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.

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 <1 year, and receipt of iodine contrast <60 days before the subsequent TSH. Cox proportional hazards regression was employed to ascertain the adjusted hazard ratio (HR) with 95% CI of incident atrial fibrillation/flutter following iodine-induced hyperthyroidism, compared with iodine-induced euthyroidism. RESULTS: Iodine-induced hyperthyroidism was observed in 2500 (5.6%) of 44 607 Veterans (mean ± SD age, 60.9 ± 14.1 years; 88% men) and atrial fibrillation/flutter in 10.4% over a median follow-up of 3.7 years (interquartile range 1.9-7.4). Adjusted for sociodemographic and cardiovascular risk factors, iodine-induced hyperthyroidism was associated with an increased risk of atrial fibrillation/flutter compared with those who remained euthyroid after iodine exposure (adjusted HR 1.19, 95% CI 1.06-1.33). Females were at greater risk for incident atrial fibrillation/flutter than males (females, HR 1.81, 95% CI 1.12-2.92; males, HR 1.15, 95% CI 1.03-1.30; P for interaction = .04). CONCLUSION: Hyperthyroidism following a high iodine load was associated with an increased risk of incident atrial fibrillation/flutter, particularly among females. The observed sex-based differences should be confirmed in a more sex-diverse study sample, and the cost-benefit analysis of long-term monitoring for cardiac arrhythmias following iodine-induced hyperthyroidism should be evaluated.

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.

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.

Background Data obtained in human lung tissue and preclinical models suggest that oxidative stress and increased apoptosis signal-regulating kinase 1 (ASK1) activity might have a prominent role in the pathobiology of pulmonary arterial hypertension (PAH). The purpose of this study was to determine the efficacy, safety, and tolerability of the ASK1 inhibitor selonsertib compared with placebo in patients with PAH. Methods We did a randomised, double-blind, placebo-controlled, phase 2 trial at 46 centres located in Canada, France, Germany, Italy, the Netherlands, Spain, the UK, and the USA. Participants were aged 18-75 years and had an established diagnosis of idiopathic or hereditary PAH, or PAH associated with connective tissue disease, drugs or toxins, human immunodeficiency virus, or repaired congenital heart defects. Patients were stratified by PAH aetiology and background therapy, and randomly assigned (1:1:1:1) using an interactive voice-response or web-response system to placebo or selonsertib 2 mg, 6 mg, or 18 mg administered orally once daily. Both placebo and selonsertib were in tablet form. The primary efficacy endpoint was change in pulmonary vascular resistance, measured by right heart catheterisation, from baseline to week 24 in the full analysis set. Pair-wise comparisons between each of the selonsertib groups and the placebo group were made with a stratified Wilcoxon (van Elteren) rank sum test for participants without major protocol deviations who received at least one dose of study drug. This trial is registered with ClinicalTrials.gov, NCT02234141. Findings Between Dec 3, 2014, and Nov 13, 2015, 151 patients were enrolled and randomly assigned. Of 150 participants who received selonsertib or placebo, 134 (89%) completed 24 weeks of the randomly assigned treatment; all were on background PAH therapy (138 [92%] on combination therapy). 90 (60%) patients were in functional class II and 60 (40%) in functional class III. Mean baseline pulmonary vascular

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 regist

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 preven

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 regist

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 preven

Real-time detection of vulnerable atherosclerotic lesions, characterized by a high content of oxidized low-density lipoprotein (oxLDL)-laden macrophages or foam cells, remains an unmet clinical need. While fractional flow reserve (FFR)-guided revascularization in angiographically intermediate stenoses is utilized to assess hemodynamic significance, in vivo detection of oxLDL-rich plaques may provide a new paradigm for treating metabolically unstable lesions. Herein, we have demonstrated endoluminal mapping of lipid-laden lesions using 3-D electrical impedance spectroscopy-derived impedance tomography (EIT) in a pre-clinical swine model. We performed surgical banding of the right carotid arteries of Yucatan mini-pigs, followed by 16 weeks of high-fat diet, to promote the development of lipid-rich lesions. We implemented an intravascular sensor combining an FFR pressure transducer with a 6-point micro-electrode array for electrical impedance spectroscopy (EIS) measurements. 3-D EIT mapping was achieved using an EIS-based reconstruction algorithm. We demonstrated that EIT mapping corresponds to endoluminal histology for oxLDL-laden lesions. We further used computational models to theoretically predict and validate EIS measurements. Thus, our 3-D EIS-derived EIT provides in vivo detection of metabolically active plaques with the goal of guiding optimal intravascular intervention.

Magnesium exhibits substantial property enhancement for a vast range of applications via alloying by rare earth elements (REs). The effect of different amounts of alloying elements (Zn and REs such as Gd, Y and Nd) on the microstructure, texture and mechanical properties of Mg has been investigated here by means of optical microscopy, electron backscattered diffraction, shear punch test and hardness test. Results indicate that the recrystallization process along the grain boundaries consists of dynamic, metadynamic and static recrystallization, while dynamic recrystallization as the dominant mechanism gives rise to bimodal microstructures in as-extruded samples with superior properties. The recrystallized area is narrow at low amounts of alloying elements, whereas addition of higher amounts of alloying elements promotes recrystallization, expands recrystallized areas and weakens texture intensity. Moreover, it is observed that there are some optimal REs ratios promoting a partially recrystallized grain structure which in turn provides higher shear strength, hardness values, and more enhanced ductility as well as a weaker texture., Peer Reviewed, Postprint (author's final draft)

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

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

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

Flexible electronics have enabled catheter-based intravascular sensing. However, real-time interrogation of unstable plaque remains an unmet clinical challenge. Here, we demonstrate the feasibility of stretchable electrochemical impedance spectroscopy (EIS) sensors for endoluminal investigations in New Zealand White (NZW) rabbits on diet-induced hyperlipidemia. A parylene C (PAC)-based EIS sensor mounted on the surface of an inflatable silicone balloon affixed to the tip of an interrogating catheter was deployed (1) on the explants of NZW rabbit aorta for detection of lipid-rich atherosclerotic lesions, and (2) on live animals for demonstration of balloon inflation and EIS measurements. An input peak-to-peak AC voltage of 10 mV and sweeping-frequency from 300 kHz to 100 Hz were delivered to the endoluminal sites. Balloon inflation allowed EIS sensors to be in contact with endoluminal surface. In the oxidized low-density-lipoprotein (oxLDL)-rich lesions from explants of fat-fed rabbits, impedance magnitude increased significantly by 1.5-fold across the entire frequency band, and phase shifted ~5° at frequencies below 10 kHz. In the lesion-free sites of the normal diet-fed rabbits, impedance magnitude increased by 1.2-fold and phase shifted ~5° at frequencies above 30 kHz. Thus, we demonstrate the feasibility of stretchable intravascular EIS sensors for identification of lipid rich lesions, with a translational implication for detecting unstable lesions.

Background The need of having feasible screening tools like Coronary Calcium Scoring (CCS) and CT Coronary Artery (CTCA) for Coronary Artery Disease (CAD) has become paramount. We aimed to evaluate the accuracy of CCS in determining the degree of stenosis of coronary vessels as compared to that determined by CTCA in a South Asian population. Methods A retrospective study was conducted at The Aga Khan University Hospital. A total of 539 patient records were reviewed who had undergone CCS and CTCA between 2008 and 2010. Patient records were reviewed by comparing their CCS and CTCA results. Results About 268 out of 301 (89%) patients with a CCS of 0–9 were found to be free of stenosis on CTCA. On a CCS of 10–99, 110 out of 121 (91%) patients were either free of stenosis or had mild stenosis. About 66 out of 79 (84%) patients had moderate or severe stenosis with a calcium score of 100–400 while none of the patients were free of stenosis. Around 28 out of 38 (74%) patients with a CCS of more than 400 had severe stenosis. However, only 04 patients (11%) were found to have mild stenosis. Spearman’s rho revealed a correlation coefficient of 0.791 with a p-value of <0.001. Conclusion Our study reaffirms that in South Asian population, low CCS (<100) is associated with no or minimal stenosis while high CCS warrants further investigation; hence, making it a reliable tool for screening patients with CAD.

Background The need of having feasible screening tools like Coronary Calcium Scoring (CCS) and CT Coronary Artery (CTCA) for Coronary Artery Disease (CAD) has become paramount. We aimed to evaluate the accuracy of CCS in determining the degree of stenosis of coronary vessels as compared to that determined by CTCA in a South Asian population. Methods A retrospective study was conducted at The Aga Khan University Hospital. A total of 539 patient records were reviewed who had undergone CCS and CTCA between 2008 and 2010. Patient records were reviewed by comparing their CCS and CTCA results. Results About 268 out of 301 (89%) patients with a CCS of 0–9 were found to be free of stenosis on CTCA. On a CCS of 10–99, 110 out of 121 (91%) patients were either free of stenosis or had mild stenosis. About 66 out of 79 (84%) patients had moderate or severe stenosis with a calcium score of 100–400 while none of the patients were free of stenosis. Around 28 out of 38 (74%) patients with a CCS of more than 400 had severe stenosis. However, only 04 patients (11%) were found to have mild stenosis. Spearman’s rho revealed a correlation coefficient of 0.791 with a p-value of <0.001. Conclusion Our study reaffirms that in South Asian population, low CCS (<100) is associated with no or minimal stenosis while high CCS warrants further investigation; hence, making it a reliable tool for screening patients with CAD.

In 2008, the European Organisation for Research and Treatment of Cancer/Mycoses Study Group (EORTC/MSG) published revised definitions for diagnosing invasive fungal disease. A previous prospective trial of liposomal amphotericin B for invasive mould disease (AmBiLoad) used modified EORTC/MSG 2002 criteria. We wished to re-evaluate the response and survival based on the revised definitions to compare the outcomes of early vs. late treatment. Patients who had received an allogeneic haematopoietic stem cell transplant or who were neutropaenic (absolute neutrophil count <500 mu l(-1) within 14 days of study entry) had been recruited on the basis of a halo or air crescent sign on chest computerised tomography. Originally classified as probable invasive mould disease, they were categorised as possible invasive mould disease using 2008 criteria. Patients had received liposomal amphotericin B at either 3 or 10 mg kg(-1) QD for 14 days, followed by 3 mg kg(-1) QD. Response at end of treatment and the 12-week survival were re-calculated according to 2008 definitions. Six-week survival was estimated by Kaplan-Meier analysis. Of 201 patients with invasive mould disease, 118 (59%) had a diagnosis based on halo signs (possible cases). Mycological evidence was present in 83 (41%) cases (probable/proven cases). Survival rates at 12 weeks for possible vs. probable/proven cases in the 3 mg kg(-1) QD group were 82% vs. 58% (P = 0.006), and 65% vs. 50% (P = 0.15) in the 10 mg kg(-1) QD group. At 6 weeks, rates were 87% vs. 69% in the 3 mg kg(-1) QD group (P = 0.009). and 75% vs. 61% in the 10 mg kg(-1) QD group (P = 0.01). Patients with possible invasive mould disease based on EORTC/MSG 2008 criteria had improved survival rates compared with those treated for probable/proven invasive mould disease. As possible invasive mould disease probably reflects an early-stage of disease, a better outcome might be expected when treatment with liposomal amphotericin B is started preemptively.

In 2008, the European Organisation for Research and Treatment of Cancer/Mycoses Study Group (EORTC/MSG) published revised definitions for diagnosing invasive fungal disease. A previous prospective trial of liposomal amphotericin B for invasive mould disease (AmBiLoad) used modified EORTC/MSG 2002 criteria. We wished to re-evaluate the response and survival based on the revised definitions to compare the outcomes of early vs. late treatment. Patients who had received an allogeneic haematopoietic stem cell transplant or who were neutropaenic (absolute neutrophil count <500 mu l(-1) within 14 days of study entry) had been recruited on the basis of a halo or air crescent sign on chest computerised tomography. Originally classified as probable invasive mould disease, they were categorised as possible invasive mould disease using 2008 criteria. Patients had received liposomal amphotericin B at either 3 or 10 mg kg(-1) QD for 14 days, followed by 3 mg kg(-1) QD. Response at end of treatment and the 12-week survival were re-calculated according to 2008 definitions. Six-week survival was estimated by Kaplan-Meier analysis. Of 201 patients with invasive mould disease, 118 (59%) had a diagnosis based on halo signs (possible cases). Mycological evidence was present in 83 (41%) cases (probable/proven cases). Survival rates at 12 weeks for possible vs. probable/proven cases in the 3 mg kg(-1) QD group were 82% vs. 58% (P = 0.006), and 65% vs. 50% (P = 0.15) in the 10 mg kg(-1) QD group. At 6 weeks, rates were 87% vs. 69% in the 3 mg kg(-1) QD group (P = 0.009). and 75% vs. 61% in the 10 mg kg(-1) QD group (P = 0.01). Patients with possible invasive mould disease based on EORTC/MSG 2008 criteria had improved survival rates compared with those treated for probable/proven invasive mould disease. As possible invasive mould disease probably reflects an early-stage of disease, a better outcome might be expected when treatment with liposomal amphotericin B is started preemptively.

Epicardial adipose tissue (EAT), pericardial adipose tissue (PAT), and subcutaneous adipose tissue (SAT) are mediators of metabolic risk and may be involved in the pathogenesis of coronary artery disease. The aim of this study was to investigate the association of visceral and subcutaneous fat depots with the presence and severity of coronary artery calcium (CAC) in asymptomatic individuals.One hundred eleven consecutive subjects underwent CAC assessment, and their Framingham risk scores were measured. EAT, total thoracic adipose tissue, and SAT volumes were measured from slice level 15 mm above to 30 mm below the ostium of the left main coronary artery. PAT was calculated as thoracic adipose tissue - EAT. SAT was defined as the volume of fat depot anterior to the sternum and posterior to the vertebra. CAC was defined as 0, 1 to 100, 101 to 400, or ≥ 400. Relative risk regression analysis was used to assess the association between fat depots and CAC.There were modest correlations between EAT (r = 0.58), PAT (r = 0.47), SAT (r = 0.34), and CAC (P < .01). EAT, PAT, and SAT increased proportionally with the severity of CAC in both genders (P < .05). After adjustment for cardiovascular risk factors and body mass index, the relative risks for each standard deviation increase in EAT, PAT, and SAT were 3.3 (95% confidence interval, 1.9-5.6), 2.7 (95% confidence interval, 1.6-3.9), and 2.6 (95% confidence interval, 1.5-4.4) for CAC ≥ 100 compared to CAC 0, respectively (P < .05). The area under the receiver-operating characteristic curve to predict CAC ≥ 100 was higher in each fat depot compared to Framingham risk score, and addition of fat depots to Framingham risk score provided maximum prognostication value to detect CAC ≥ 100.Increased EAT, PAT, and SAT are associated with the severity of CAC independent of risk factors.

Epicardial adipose tissue (EAT), pericardial adipose tissue (PAT), and subcutaneous adipose tissue (SAT) are mediators of metabolic risk and may be involved in the pathogenesis of coronary artery disease. The aim of this study was to investigate the association of visceral and subcutaneous fat depots with the presence and severity of coronary artery calcium (CAC) in asymptomatic individuals.One hundred eleven consecutive subjects underwent CAC assessment, and their Framingham risk scores were measured. EAT, total thoracic adipose tissue, and SAT volumes were measured from slice level 15 mm above to 30 mm below the ostium of the left main coronary artery. PAT was calculated as thoracic adipose tissue - EAT. SAT was defined as the volume of fat depot anterior to the sternum and posterior to the vertebra. CAC was defined as 0, 1 to 100, 101 to 400, or ≥ 400. Relative risk regression analysis was used to assess the association between fat depots and CAC.There were modest correlations between EAT (r = 0.58), PAT (r = 0.47), SAT (r = 0.34), and CAC (P < .01). EAT, PAT, and SAT increased proportionally with the severity of CAC in both genders (P < .05). After adjustment for cardiovascular risk factors and body mass index, the relative risks for each standard deviation increase in EAT, PAT, and SAT were 3.3 (95% confidence interval, 1.9-5.6), 2.7 (95% confidence interval, 1.6-3.9), and 2.6 (95% confidence interval, 1.5-4.4) for CAC ≥ 100 compared to CAC 0, respectively (P < .05). The area under the receiver-operating characteristic curve to predict CAC ≥ 100 was higher in each fat depot compared to Framingham risk score, and addition of fat depots to Framingham risk score provided maximum prognostication value to detect CAC ≥ 100.Increased EAT, PAT, and SAT are associated with the severity of CAC independent of risk factors.

Treatment of invasive mold infection in immunocompromised patients remains challenging. Voriconazole has been shown to have efficacy and survival benefits over amphotericin B deoxycholate, but its utility is limited by drug interactions. Liposomal amphotericin B achieves maximum plasma levels at a dosage of 10 mg/kg per day, but clinical efficacy data for higher doses are lacking., Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't, SCOPUS: ar.j, info:eu-repo/semantics/published

Treatment of invasive mold infection in immunocompromised patients remains challenging. Voriconazole has been shown to have efficacy and survival benefits over amphotericin B deoxycholate, but its utility is limited by drug interactions. Liposomal amphotericin B achieves maximum plasma levels at a dosage of 10 mg/kg per day, but clinical efficacy data for higher doses are lacking., Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't, SCOPUS: ar.j, info:eu-repo/semantics/published

BackgroundAtorvastatin is a synthetic inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase. In placebo-controlled trials, it has been shown to achieve significant dose-dependent reductions in low-density lipoprotein cholesterol, total cholesterol, and triglycerides. This trial compared the efficacy of daily atorvastatin administration with that of alternate-day dosing.MethodsThis was a randomized, prospective, nonblinded, controlled clinical trial. Fifty-four patients with low-density lipoprotein cholesterol of 100 to 200 mg/dL were enrolled. Baseline fasting lipid profile (total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglycerides), liver function tests (aspartate transaminase and alanine aminotransferase), and creatine kinase were drawn. Patients were randomized to three atorvastatin dose groups. Group I received 10 mg of atorvastatin every day, Group II received 10 mg every other day, and Group III received 20 mg every other day. After 6 weeks of treatment with atorvastatin, fasting lipid profiles, liver function tests, and creatine kinase concentrations were redrawn. Compliance to treatment was assessed at each visit.ResultsOf the 54 patients enrolled, 46 completed the study. All three regimens significantly reduced total cholesterol and low-density lipoprotein cholesterol compared to baseline. No statistically significant differences existed between the three groups in regards to total, or a percentage, decrease in total cholesterol and low-density lipoprotein cholesterol at 6 weeks compared to baseline. All regimens were well tolerated and none of the patients had a significant elevation of liver enzymes or creatine kinase during the course of the study.ConclusionAlternate-day dosing of atorvastatin is an efficacious and safe alternative to daily dosing.

BackgroundAtorvastatin is a synthetic inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase. In placebo-controlled trials, it has been shown to achieve significant dose-dependent reductions in low-density lipoprotein cholesterol, total cholesterol, and triglycerides. This trial compared the efficacy of daily atorvastatin administration with that of alternate-day dosing.MethodsThis was a randomized, prospective, nonblinded, controlled clinical trial. Fifty-four patients with low-density lipoprotein cholesterol of 100 to 200 mg/dL were enrolled. Baseline fasting lipid profile (total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglycerides), liver function tests (aspartate transaminase and alanine aminotransferase), and creatine kinase were drawn. Patients were randomized to three atorvastatin dose groups. Group I received 10 mg of atorvastatin every day, Group II received 10 mg every other day, and Group III received 20 mg every other day. After 6 weeks of treatment with atorvastatin, fasting lipid profiles, liver function tests, and creatine kinase concentrations were redrawn. Compliance to treatment was assessed at each visit.ResultsOf the 54 patients enrolled, 46 completed the study. All three regimens significantly reduced total cholesterol and low-density lipoprotein cholesterol compared to baseline. No statistically significant differences existed between the three groups in regards to total, or a percentage, decrease in total cholesterol and low-density lipoprotein cholesterol at 6 weeks compared to baseline. All regimens were well tolerated and none of the patients had a significant elevation of liver enzymes or creatine kinase during the course of the study.ConclusionAlternate-day dosing of atorvastatin is an efficacious and safe alternative to daily dosing.