Impact of Guideline-Directed Statin Prescriptions on Cardiovascular Outcomes by Race in a Real-World Primary Prevention Cohort.

Background: Data on real-world statin prescription in large, private health care networks and impacts on primary prevention of atherosclerotic cardiovascular disease (ASCVD) outcomes across race are scarce. Objectives: The purpose of this study was to investigate the impact of statin prescription on ASCVD outcomes within and across race in a large, nongovernmental health care system. Methods: Statin prescription in Black and White patients without ASCVD was evaluated (2013-2019). Guideline-directed statin intensity was defined as at least "moderate" for intermediate and high-risk patients. Statin prescription at index and ASCVD outcomes at follow-up (myocardial infarction/revascularization, stroke, mortality) were assessed via electronic health care records using International Classification of Diseases-9 and 10 codes. Cox regression models, adjusted for CVD risk factors, were used to calculate HRs for association between statin prescription and incident ASCVD events across race. Results: Among 270,079 patients, 7.6% (n = 20,477) and 92.4% (n = 249,602) identified as Black and White, respectively. Significantly fewer Black patients were prescribed statin therapy than White patients (13.6% vs 19.0%; P < 0.001). At a mean follow-up of 6 years, patients with "no statin" prescription vs guideline-directed statin intensity showed increased ASCVD in Black patients (HR: 1.40 [95% CI: 1.05-1.86]), and White patients (HR: 1.32 [95% CI: 1.21-1.45]; P < 0.05) and all-cause mortality. Intermediate and high-risk Black patients faced a 17% higher risk of mortality compared to White patients. However, the interaction between race and statin prescription was not a significant predictor of incident ASCVD events. Conclusions: Statins remain underprescribed. Although Black patients received proportionally less statin prescription than White patients, this was not associated with higher risk of mortality in Black patients.

The Method of Lipemia Clearance Should be Based on the Characteristics and the Method of Testing in the Emergency Laboratory.

BACKGROUND: This study aimed to compare the lipemia removal efficiency of highspeed centrifugation, lipid scavengers, and dilution for biochemical analytes. METHODS: We collected 30 cases of lipemic plasma in an emergency laboratory and divided them into 4 aliquots. Lipemia was removed by highspeed centrifugation, lipid scavenger, dilution, and ultracentrifugation, then analytes were measured by an AU5800 analyzer. Taking ultracentrifugation as reference, the efficiencies of the other three methods were evaluated based on the deviation. RESULTS: When highspeed centrifugation was used for lipemia removal, DBIL (18.62%), and Magnesium (6.09%) could not satisfy the criterion. When lipid scavengers were applied to remove lipemia, CRP (-86.70%), TP (-8.29%), CKMB (-44.85%), DBIL (37.96%), Glu (4.20%) and phosphate (14.32%) were not suggested as lipid scavengers. For dilution, nearly half of the analytes could satisfy the criterion, including AMY (2.41%), CRP (5.54%), ALT (2.85%), GGTL (-1.73%), ALP (-0.04%), Glu (-0.84%), LDH (0.06%), CK (0.68%), BUN (3.80%), CREA (-1.54%), UA (5.42%), and magnesium (0.43%). CONCLUSIONS: Neither of the methods for lipid removal could satisfy all emergency department tests for lipid removal. This finding suggests that removing lipemia in the clinical laboratory should be based on the characteristics and the method of testing.

Impact of Weight Gain on Cardiovascular Outcomes in Patients With Atrial Fibrillation.

BACKGROUND: The long-term impact of weight gain (WG) on cardiovascular outcomes among patients with atrial fibrillation (AF) is unclear. METHODS AND RESULTS: We studied 62 871 (mean age, 72±12, 43% women) adult patients with AF evaluated at the University of Pittsburgh Medical Center between January 1, 2010, and May 13, 2021. Serial body mass index, risk factors, comorbidities, and subsequent death and hospitalization were ascertained and stratified according to percentage WG (≥0% to <5%, ≥5% to <10%, and ≥10%). Over 4.9±3.19 years of follow-up, 27 114 (43%) patients gained weight (61%, ≥0% to <5%; 23%, ≥5% to <10%; 16%, ≥10%). Patients with progressive WG were incrementally younger (P<0.001) women (40%, 42%, and 47%) with lower median household income (P=0.002) and active smoking (8%, 13% and 13%), and they were less likely to be on a non-vitamin K oral anticoagulant (39%, 37%, and 32%). WG was incrementally associated with a significant increase in risk of hospitalization for AF (≥10% WG; hazard ratio [HR], 1.2 [95% CI, 1.2-1.3]; P<0.0001), heart failure (≥10% WG; HR, 1.44 [95% CI, 1.3-1.6]; P<0.001; ≥5% to <10% WG; HR, 1.17 [95% CI, 1.1-1.2]; P<0.001), myocardial infarction (≥10% WG; HR, 1.2 [95% CI, 1.3-1.6]; P<0.001) and all-cause stroke (4.2%, 4.3%, and 5.6%) despite significantly lower mean CHADS2Vasc score (2.9±1.7, 2.7±1.6, and 2.7±1.7). Patients with more WG were significantly more likely to receive cardiac and electrophysiologic interventions. CONCLUSIONS: Among patients with AF, WG is incrementally associated with increased hospitalization for cardiovascular causes, particularly heart failure, stroke, myocardial infarction, and AF.

Sex-based utilization of guideline recommended statin therapy and cardiovascular disease outcomes: Data from a multisite healthcare network primary prevention cohort.

Background: In the US, women have similar cardiovascular death rates as men. However, less is known about sex differences in statin use for primary prevention and associated atherosclerotic cardiovascular disease (ASCVD) outcomes. Methods: Statin prescriptions using electronic health records were examined in patients without ASCVD (myocardial infarction (MI), revascularization or ischemic stroke) between 2013 and 2019. Guideline-directed statin intensity (GDSI) at index (at least moderate intensity, defined per pooled-cohort equation) and follow-up visits were compared between sexes across ASCVD risk groups, defined by the pooled-cohort equation. Cox regression hazard ratios were calculated for statin use and outcomes (myocardial infarction, stroke/transient ischemic attack (TIA), and all-cause mortality) stratified by sex. Interaction terms (statin and sex) were applied. Results: Among 282,298 patients, (mean age ∼ 50 years) 17.1 % women and 19.5 % men were prescribed any statin at index visit. Time to GDSI was similar between sexes, but the proportion of high-risk women on GDSI at follow-up were lower compared to high-risk men (2-years: 27.7 vs 32.0 %, and 5-years: 47.2 vs 55.2 %, p < 0.05). When compared to GDSI, no statin use was associated with higher risk of MI and ischemic stroke/TIA among both sexes. High-risk women on GDSI had a lower risk of mortality (HR=1.39 [1.22-1.59]) vs. men (HR=1.67 [1.50-1.86]) of similar risk (p value interaction=0.004). Conclusion: In a large contemporary healthcare system, there was underutilization of statins across both sexes in primary prevention. High-risk women were less likely to remain on GDSI compared to high-risk men. GDSI significantly improved the survival in both sexes regardless of ASCVD risk group. Future strategies to ensure continued use of GDSI, specifically among women, should be explored.

Association of Hypertensive Disorders of Pregnancy With Coronary Microvascular Dysfunction 8 to 10 Years After Delivery.

BACKGROUND: Hypertensive disorders of pregnancy (HDP) are associated with subsequent adverse cardiac remodeling and cardiovascular disease. The role of myocardial microvascular disease among individuals with HDP and left ventricular (LV) remodeling as a potential link to cardiovascular disease is unknown. We aimed to determine whether individuals with HDP history have coronary microvascular dysfunction measured by coronary flow reserve 8 to 10 years after delivery and whether microvascular dysfunction correlates with LV remodeling. METHODS: Individuals with pregnancies delivered from 2008 to 2010 underwent burst-replenishment myocardial contrast echocardiography (2017-2020) to quantify myocardial perfusion at rest and during dobutamine stress. Video intensity versus time data were used to derive ß, the rate of rise of video intensity, a correlate for myocardial blood flow. Coronary flow reserve was calculated as the ratio of ß at peak stress to ß at rest, averaged across LV myocardial regions of interest. RESULTS: We studied 91 individuals (aged 38±6 and 9.1±0.9 years postdelivery) and 19 with a history of HDP. Individuals with coronary microvascular dysfunction (coronary flow reserve <2.0; n=13) had a higher proportion of HDP (46.2% versus 16.7%; P=0.026) and higher prepregnancy body mass index, baseline heart rate, and hemoglobin A1c compared with those without microvascular dysfunction. The association of coronary flow reserve and HDP was attenuated after adjusting for cardiometabolic factors (P=0.133). In exploratory subgroup analyses, individuals with both LV remodeling (relative wall thickness >0.42) and HDP (n=12) had the highest proportion of microvascular dysfunction (41.7% versus +HDP-LV remodeling [n=7] 14.3%; -HDP+LV remodeling [n=26] 7.7%; P=0.0498). CONCLUSIONS: In this small study, HDP history is associated with coronary microvascular dysfunction 1 decade after delivery, findings that may, in part, be driven by metabolic factors including obesity and diabetes. Microvascular dysfunction may contribute to cardiovascular disease among individuals with a history of HDP.

Ultrasound enhanced siRNA delivery using cationic liposome-microbubble complexes for the treatment of squamous cell carcinoma.

Rationale: Microbubble (MB) contrast agents combined with ultrasound targeted microbubble cavitation (UTMC) are a promising platform for site-specific therapeutic oligonucleotide delivery. We investigated UTMC-mediated delivery of siRNA directed against epidermal growth factor receptor (EGFR), to squamous cell carcinoma (SCC) via a novel MB-liposome complex (LPX). Methods: LPXs were constructed by conjugation of cationic liposomes to the surface of C4F10 gas-filled lipid MBs using biotin/avidin chemistry, then loaded with siRNA via electrostatic interaction. Luciferase-expressing SCC-VII cells (SCC-VII-Luc) were cultured in Petri dishes. The Petri dishes were filled with media in which LPXs loaded with siRNA against firefly luciferase (Luc siRNA) were suspended. Ultrasound (US) (1 MHz, 100-µs pulse, 10% duty cycle) was delivered to the dishes for 10 sec at varying acoustic pressures and luciferase assay was performed 24 hr later. In vivo siRNA delivery was studied in SCC-VII tumor-bearing mice intravenously infused with a 0.5 mL saline suspension of EGFR siRNA LPX (7×108 LPX, ~30 µg siRNA) for 20 min during concurrent US (1 MHz, 0.5 MPa spatial peak temporal peak negative pressure, five 100-µs pulses every 1 ms; each pulse train repeated every 2 sec to allow reperfusion of LPX into the tumor). Mice were sacrificed 2 days post treatment and tumor EGFR expression was measured (Western blot). Other mice (n=23) received either EGFR siRNA-loaded LPX + UTMC or negative control (NC) siRNA-loaded LPX + UTMC on days 0 and 3, or no treatment ("sham"). Tumor volume was serially measured by high-resolution 3D US imaging. Results: Luc siRNA LPX + UTMC caused significant luciferase knockdown vs. no treatment control, p<0.05) in SCC-VII-Luc cells at acoustic pressures 0.25 MPa to 0.9 MPa, while no significant silencing effect was seen at lower pressure (0.125 MPa). In vivo, EGFR siRNA LPX + UTMC reduced tumor EGFR expression by ~30% and significantly inhibited tumor growth by day 9 (~40% decrease in tumor volume vs. NC siRNA LPX + UTMC, p<0.05). Conclusions: Luc siRNA LPXs + UTMC achieved functional delivery of Luc siRNA to SCC-VII-Luc cells in vitro. EGFR siRNA LPX + UTMC inhibited tumor growth and suppressed EGFR expression in vivo, suggesting that this platform holds promise for non-invasive, image-guided targeted delivery of therapeutic siRNA for cancer treatment.

Mortality, Hospitalization, and Cardiac Interventions in Patients With Atrial Fibrillation Aged <65 Years.

BACKGROUND: The risk factor (RF) burden, clinical course, and long-term outcome among patients with atrial fibrillation (AF) aged <65 years is unclear. METHODS: Adult (n=67 221; mean age, 72.4±12.3 years; and 45% women) patients with AF evaluated at the University of Pittsburgh Medical Center between January 2010 and December 2019 were studied. Hospital system-wide electronic health records and administrative data were utilized to ascertain RFs, comorbidities, and subsequent hospitalization and cardiac interventions. The association of AF with all-cause mortality among those aged <65 years was analyzed using an internal contemporary cohort of patients without AF (n=918 073). RESULTS: Nearly one-quarter (n=17 335) of the cohort was aged <65 years (32% women) with considerable cardiovascular RFs (current smoker, 16%; mean body mass index, 33.0±8.3; hypertension, 55%; diabetes, 21%; heart failure, 20%; coronary artery disease, 19%; and prior ischemic stroke, 6%) and comorbidity burden (chronic obstructive pulmonary disease, 11%; obstructive sleep apnea, 18%; and chronic kidney disease, 1.3%). Over mean follow-up of >5 years, 2084 (6.7%, <50 years; 13%, 50-65 years) patients died. The proportion of patients with >1 hospitalization for myocardial infarction, heart failure, and stroke was 1.3%, 4.8%, and 1.1% for those aged <50 years and 2.2%, 7.4%, and 1.1% for the 50- to 65-year subgroup, respectively. Multiple cardiac and noncardiac RFs were associated with increased mortality in younger patients with AF with heart failure and hypertension demonstrating significant age-related interaction (P=0.007 and P=0.013, respectively). Patients with AF aged <65 years experienced significantly worse survival compared with comorbidity-adjusted patients without AF (men aged <50 years and hazard ratio, 1.5 [95% CI, 1.24-1.79]; 50-65 years and hazard ratio, 1.3 [95% CI, 1.26-1.43]; women aged <50 years and hazard ratio, 2.4 [95% CI, 1.82-3.16]; 50-65 years and hazard ratio, 1.7 [95% CI, 1.6-1.92]). CONCLUSIONS: Patients with AF aged <65 years have significant comorbidity burden and considerable long-term mortality. They are also at a significantly increased risk of hospitalization for heart failure, stroke, and myocardial infarction. These patients warrant an aggressive focus on RF and comorbidity evaluation and management.

Statin utilization and cardiovascular outcomes in a real-world primary prevention cohort of older adults.

Background: Statins are a cost-effective therapy for prevention of atherosclerotic cardiovascular disease (ASCVD). Guidelines on statins for primary prevention are unclear for older adults (>75 years). Objective: Investigate statin utility in older adults without ASCVD events, by risk stratifying in a large healthcare network. Methods: We included 8,114 older adults, without CAD, PVD or ischemic stroke. Statin utilization based on ACC/AHA 10-year ASCVD risk calculation, was evaluated in intermediate (7.5%-19.9%) and high-risk patients (≥ 20%); and categorized using low and 'moderate or high' intensity statins with a follow up period of ∼7 years. Cox regression models were used to calculate hazard ratios for incident ASCVD and mortality across risk categories stratified by statin utilization. Data was adjusted for competing risk using Elixhauser Comorbidity Index. Results: Compared with those on moderate or high intensity statins, high-risk older patients not on any statin had a significantly increased risk of MI [HR 1.51 (1.17-1.95); p<0.01], stroke [HR 1.47 (1.14-1.90); p<0.01] and all-cause mortality [HR 1.37 (1.19-1.58); p<0.001] in models adjusted for Elixhauser Comorbidity Index. When comparing the no statin group versus the moderate or high intensity statin group in the intermediate risk cohort, although a trend for increased risk was seen, it did not meet statistical significance thresholds for MI, stroke or all-cause mortality. Conclusion: Lack of statin use was associated with increased cardiovascular events and mortality in high-risk older adults. Given the benefits appreciated, statin use may need to be strongly considered for primary ASCVD prevention among high-risk older adults. Future studies will assess the risk-benefit ratio of statin intervention in older adults.

Effect of an Arsenic Mitigation Program on Arsenic Exposure in American Indian Communities: A Cluster Randomized Controlled Trial of the Community-Led Strong Heart Water Study Program.

BACKGROUND: Chronic arsenic exposure has been associated with an increased risk of cardiovascular disease; diabetes; cancers of the lung, pancreas and prostate; and all-cause mortality in American Indian communities in the Strong Heart Study. OBJECTIVE: The Strong Heart Water Study (SHWS) designed and evaluated a multilevel, community-led arsenic mitigation program to reduce arsenic exposure among private well users in partnership with Northern Great Plains American Indian Nations. METHODS: A cluster randomized controlled trial (cRCT) was conducted to evaluate the effectiveness of the SHWS arsenic mitigation program over a 2-y period on a) urinary arsenic, and b) reported use of arsenic-safe water for drinking and cooking. The cRCT compared the installation of a point-of-use arsenic filter and a mobile Health (mHealth) program (3 phone calls; SHWS mHealth and Filter arm) to a more intensive program, which included this same program plus three home visits (3 phone calls and 3 home visits; SHWS Intensive arm). RESULTS: A 47% reduction in urinary arsenic [geometric mean (GM)=13.2 to 7.0µg/g creatinine] was observed from baseline to the final follow-up when both study arms were combined. By treatment arm, the reduction in urinary arsenic from baseline to the final follow-up visit was 55% in the mHealth and Filter arm (GM=14.6 to 6.55µg/g creatinine) and 30% in the Intensive arm (GM=11.2 to 7.82µg/g creatinine). There was no significant difference in urinary arsenic levels by treatment arm at the final follow-up visit comparing the Intensive vs. mHealth and Filter arms: GM ratio of 1.21 (95% confidence interval: 0.77, 1.90). In both arms combined, exclusive use of arsenic-safe water from baseline to the final follow-up visit significantly increased for water used for cooking (17% to 53%) and drinking (12% to 46%). DISCUSSION: Delivery of the interventions for the community-led SHWS arsenic mitigation program, including the installation of a point-of-use arsenic filter and a mHealth program on the use of arsenic-safe water (calls only, no home visits), resulted in a significant reduction in urinary arsenic and increases in reported use of arsenic-safe water for drinking and cooking during the 2-y study period. These results demonstrate that the installation of an arsenic filter and phone calls from a mHealth program presents a promising approach to reduce water arsenic exposure among private well users. https://doi.org/10.1289/EHP12548.

Sex-Based Utilization of Guideline Recommended Statin Therapy and Cardiovascular Disease Outcomes: A Primary Prevention Healthcare Network Registry.

Background: In the US, women have similar cardiovascular death rates than men. Less is known about sex differences in statin use for primary prevention and associated atherosclerotic cardiovascular disease (ASCVD) outcomes. Methods: Statin prescriptions using electronic health records were examined in patients without ASCVD (myocardial infarction (MI), revascularization or ischemic stroke) between 2013-2019. Guideline-directed statin intensity (GDSI) at index and follow-up visits were compared among sexes across ASCVD risk groups, defined by pooled-cohort equation. Cox regression hazard ratios (HR) [95% CI] were calculated for statin use and outcomes (myocardial infarction, stroke/transient ischemic attack (TIA), and all-cause mortality) stratified by sex. Interaction terms (statin and sex) were applied. Results: Among 282,298 patients, (mean age ∼ 50 years) 17.1% women and 19.5% men were prescribed any statin at index visit. Time to GDSI was similar between sexes, but the proportion of high-risk women on GDSI at follow-ups was lower compared to high-risk men (2-years: 27.7 vs 32.0%, and 5-years: 47.2 vs 55.2%, p<0.05). When compared to GDSI, no statin use was associated with higher risk of MI and ischemic stroke/TIA amongst both sexes. High-risk women on GDSI had a lower risk of mortality (HR=1.39 [1.22-1.59]) versus men (HR=1.67 [1.50-1.86]) of similar risk (p value interaction=0.004). Conclusion: In a large contemporary healthcare system, there was underutilization of statins across both sexes in primary prevention. High-risk women were less likely to be initiated on GDSI compared with high-risk men. GDSI significantly improved the survival in both sexes regardless of ASCVD risk group. Future strategies to ensure continued use of GDSI, specifically among women, should be explored.

Outcomes of Aortomitral Continuity Reconstruction During Concomitant Aortic and Mitral Valve Replacement.

OBJECTIVES: To describe outcomes of reconstruction of the aortomitral continuity (AMC) during concomitant aortic and mitral valve replacement (ie, the "Commando" procedure). DESIGN: A retrospective study of consecutive cardiac surgeries from 2010 to 2022. SETTING: At a single institution. PARTICIPANTS: All patients undergoing double aortic and mitral valve replacement. INTERVENTIONS: Patients were dichotomized by the performance (or not) of AMC reconstruction. MEASUREMENTS AND MAIN RESULTS: A total of 331 patients underwent double-valve replacement, of whom 21 patients (6.3%) had a Commando procedure. The Commando group was more likely to have had a previous aortic valve replacement (AVR) or mitral valve replacement (MVR) (66.7% v 27.4%, p < 0.001), redo cardiac surgery (71.4% v 31.3%, p < 0.001), and emergent/salvage surgery (14.3% v 1.61%, p = 0.001), whereas surgery was more often performed for endocarditis in the Commando group (52.4% v 22.9%, p = 0.003). The Commando group had higher operative mortality (28.6% v 10.7%, p = 0.014), more prolonged ventilation (61.9% v 31.9%, p = 0.005), longer cardiopulmonary bypass time (312 ± 118 v 218 ± 85 minutes, p < 0.001), and longer ischemic time (252 ± 90 v 176 ± 66 minutes, p < 0.001). Despite increased short-term morbidity in the Commando group, Kaplan-Meier survival estimation showed no difference in long-term survival between each group (p = 0.386, log-rank). On multivariate Cox analysis, the Commando procedure was not associated with an increased hazard of death, compared to MVR + AVR (hazard ratio 1.29, 95% CI: 0.65-2.59, p = 0.496). CONCLUSIONS: Although short-term postoperative morbidity and mortality were found to be higher for patients undergoing the Commando procedure, AMC reconstruction may be equally durable in the long term.

Achieving highly stable sodium metal batteries with self-adapting and high-ionic-mobility ceramic fiber membranes.

Tough issues like sodium (Na) dendrite growth and poor anode reversibility hinder the practical application of sodium metal batteries (SMBs) with moderate liquid electrolytes. To settle these problems, using a smart self-adapting Al2SiO5 ceramic fiber (CF) membrane is demonstrated to enable homogeneous Na depositions and inhibit the dendritic growth. This inorganic membrane itself has superb thermal stability, high ionic mobility (Na+ transference number: 0.65) and electrolyte wettability over traditional glass fiber (GF) or polymeric ones, guaranteeing the low voltage polarization (14 mV) and long-cyclic lifetime (over 600 h) in symmetric cells testing. Notably, aluminous components in CF membranes would interact with F-based molecules in the electrolyte phase, thereby releasing some Al3+ species that can be electrochemically deposited onto the anodic interface. The packed (+)Na3V2(PO4)3|CF|Na(-) full SMBs exhibit far superior cyclic stability (capacity retention over 78.7 % after 600 cycles at 1C) than other counterparts. The in-situ detection/postmortem analysis reveal that Al/F-based inorganics formed in as-built SEI layers play a vital role in Na metal anode protection. This work may provide a viable strategy to overcome the constraints of high-energy SMBs in practical applications.

Unlocking the Design Paradigm of In-Plane Heterojunction with Built-in Bifunctional Anion Vacancy for Unexpectedly Fast Sodium Storage.

Transition metal chalcogenide (TMD) electrodes in sodium-ion batteries exhibit intrinsic shortcomings such as sluggish reaction kinetics, unstable conversion thermodynamics, and substantial volumetric strain effects, which lead to electrochemical failure. This report unlocks a design paradigm of VSe2- x /C in-plane heterojunction with built-in anion vacancy, achieved through an in situ functionalization and self-limited growth approach. Theoretical and experimental investigations reveal the bifunctional role of the Se vacancy in enhancing the ion diffusion kinetics and the structural thermodynamics of Nax VSe2 active phases. Moreover, this in-plane heterostructure facilitates complete face contact between the two components and tight interfacial conductive contact between the conversion phases, resulting in enhanced reaction reversibility. The VSe2- x /C heterojunction electrode exhibits remarkable sodium-ion storage performance, retaining specific capacities of 448.7 and 424.9 mAh g-1 after 1000 cycles at current densities of 5 and 10 A g-1 , respectively. Moreover, it exhibits a high specific capacity of 353.1 mAh g-1 even under the demanding condition of 100 A g-1 , surpassing most previous achievements. The proposed strategy can be extended to other V5 S8- x and V2 O5- x -based heterojunctions, marking a conceptual breakthrough in advanced electrode design for constructing high-performance sodium-ion batteries.

Reinterventions After Repair of Acute Type A Aortic Dissection: Incidence, Outcomes, and Risk Factors.

BACKGROUND: This study reports the incidence, outcomes, and risk factors for aortic reinterventions after repair of acute type A aortic dissection (ATAAD). METHODS: This was an observational study of aortic operations from 2010 to 2021. All patients with ATAAD undergoing open aortic arch reconstruction were included. Patients were dichotomized by the need for reintervention, which included reinterventions proximal to or distal to the index aortic repair. Propensity matching was used to determine the impact of reintervention on long-term outcomes. The cumulative incidence function for reintervention was estimated, and multivariable Fine-Gray analysis was performed to identify variables associated with reintervention, with death treated as a competing event. RESULTS: We identified 601 patients undergoing surgery for ATAAD. An aortic reintervention was required in 71 (11.8%), comprising a proximal reintervention in 12 patients, a distal reintervention in 56, and both in 3. The cumulative incidence of reintervention was 11.6% (95% CI, 8.9%-14.6%) at 5 years and was 16.0% (95% CI, 12.2%-20.3%) at 10 years, with a median time to reintervention of 4.0 years (interquartile range, 0.9-7.5 years). Multivariable analysis using the Fine-Gray method showed no operative variables were associated with reinterventions. Among the 71 reinterventions, there were 4 (5.6%) operative deaths. After propensity matching, there was no difference in Kaplan-Meier survival estimates across each group (P = .138 by log-rank statistics). CONCLUSIONS: The cumulative incidence of aortic reintervention after ATAAD repair was reasonably low (16% at 10 years), reinterventions were relatively safe (6% operative mortality), and reinterventions did not significantly impact long-term survival.

Impact of Guideline-Directed Statin Intervention for Primary Prevention in Patients With Diabetes.

OBJECTIVE: We examined guideline-directed statin intensity (GDSI) use and atherosclerotic cardiovascular disease (ASCVD) outcomes in patients with diabetes across a contemporary health care system. RESEARCH DESIGN AND METHODS: Patients without preexisting ASCVD were categorized by diabetes status and 10-year ASCVD risk (borderline [5-7.4%], intermediate [7.5-19.9%], high [≥20%]). Mean ±SD time to start of or change to GDSI was calculated. Incident ASCVD and all-cause mortality association, stratified by ASCVD risk, was calculated using Cox regression. RESULTS: Among 282,298 patients, 28,807 (10.2%) had diabetes and 253,491 (89.8%) did not. Only two-thirds of intermediate- and high-risk patients with diabetes were receiving GDSI therapy at 5-year follow-up. In fully adjusted models, patients with diabetes not taking a statin (vs. GDSI) had a significantly higher risk of stroke and mortality in the intermediate- and high-risk groups (hazard ratio for mortality 1.81 [95% CI 1.58-2.07] vs. 1.41 [1.26-1.57]; P for interaction < 0.01). CONCLUSIONS: Significant gaps remain in GDSI use for high-risk patients with diabetes, conferring an increased risk of ASCVD outcomes and all-cause mortality.

Lower-extremity malperfusion syndrome in patients undergoing proximal aortic surgery for acute type A aortic dissection.

Objective: Data regarding management of lower-extremity malperfusion in the setting of type A aortic dissection are limited. This study aimed to compare acute type A aortic dissection with lower-extremity malperfusion outcomes in patients undergoing lower-extremity revascularization with no revascularization. Methods: Consecutive patients undergoing acute type A aortic dissection surgery were identified from a prospectively maintained database. Perioperative variables were compared between patients with and without lower-extremity malperfusion. Factors associated with lower-extremity malperfusion, revascularization, and mortality were determined using univariable Cox regression and Firth's penalized likelihood modeling. Results: From January 2007 to December 2021, 601 patients underwent proximal aortic repair for acute type A aortic dissection at a quaternary care center. Of these, 85 of 601 patients (14%) presented with lower-extremity malperfusion and were more often male (P = .02), had concomitant moderate or greater aortic insufficiency (P = .05), had lower ejection fraction (P = .004), had preoperative dialysis dependence (P = .01), and had additional cerebral, visceral, and renal malperfusion syndromes (P < .001). Kaplan-Meier estimated survival fared worse with lower-extremity malperfusion compared with no lower-extremity malperfusion at 1, 5, and 10 years (84% vs 77%, 74% vs 71%, 65% vs 52%, respectively, P = .03). In the lower-extremity malperfusion group, 15 of 85 patients (18%) underwent lower-extremity revascularization without significant differences in postoperative morbidity and mortality compared with patients not undergoing revascularization. Need for peripheral revascularization was associated with peripheral vascular disease (hazard ratio, 3.7 [1.0-14.0], P = .05) and pulse deficit (hazard ratio, 5.6 [1.3-24.0], P = .02) at presentation. Conclusions: Patients presenting with type A aortic dissection and lower-extremity malperfusion have worse overall survival compared with those without lower-extremity malperfusion. However, not all patients with type A aortic dissection and lower-extremity malperfusion require revascularization.

Ultrasound-Induced Microbubble Cavitation for Targeted Delivery of MiR-29b Mimic to Treat Cardiac Fibrosis.

OBJECTIVE: Cardiac fibrosis contributes to adverse ventricular remodeling and is associated with loss of miR-29b. Overexpression of miR-29b via plasmid or intravenous injection of microRNA mimic has blunted fibrosis, but these are inefficient and non-targeted delivery strategies. In this study, we tested the hypothesis that delivery of microRNA-29b (miR-29b) using ultrasound-targeted microbubble cavitation (UTMC) of miR-29b-loaded microbubbles would attenuate cardiac fibrosis and preserve left ventricular (LV) function. METHODS: Lipid microbubbles were loaded with miR-29b mimic (miR-29b-MB) or negative control (NC) mimic (NC-MB), placed with cardiac fibroblasts (CFs) and treated with pulsed ultrasound. Cells were harvested to measure downstream fibrotic mediators. Mice received angiotensin II (ANG II) infusion causing afterload increase and direct ANG II-induced cardiac fibrosis. UTMC of miRNA-loaded microbubbles was administered to the heart at days 0, 3 and 7. Serial echocardiography was performed, and hearts were harvested on day 10. RESULTS: UTMC treatment of CFs with miR-29b-MB increased miR-29b and decreased fibrotic transcripts compared with NC-MB treatment. In vivo UTMC + NC-MB led to increased LV mass, reduction in cardiac function and increase in fibrotic markers, demonstrating ANGI II-induced adverse cardiac remodeling. Mice treated with UTMC + miR-29b-MB had preservation of cardiac function, downregulation of cardiac fibrillin and trends of lower COL1A1, COL1A2 and COL3 mRNA and decreased cardiac α-smooth muscle protein. CONCLUSION: UTMC-mediated delivery of miR-29b mimic blunts expression of fibrosis markers and preserves LV function in ANG II-induced cardiac fibrosis.

Oscillator Strengths and Cross Sections of the Valence-Shell Excitations of HBr Studied by Fast Electron Impact.

The oscillator strengths and cross sections of the valence-shell excitations of HBr were determined by fast electron scattering with an incident electron energy of 1500 eV and an energy resolution of 80 meV. The momentum transfer dependence behaviors of the generalized oscillator strengths have been used to elucidate the transition characteristics. The present results show that the strong spin-orbital interaction results in the observation of some triplet states in the (Λ, S) coupling and the constant generalized oscillator strength ratios for the pair states with the same electronic configuration and quantum number Ω, and the quantitative spin-orbit coupling coefficients of b3Π1(v = 0) and C1Π(v = 0) are determined. The optical oscillator strengths of the valence-shell excitations were obtained by extrapolating the generalized oscillator strengths to the limit of zero squared momentum transfer. The present optical oscillator strengths give an independent cross-check of the previous experimental and theoretical results, and the comparison shows that the line-saturation effect is more severe for the high Rydberg states with large intensities and narrow natural widths. The integral cross sections of the valence-shell excitations of HBr were obtained from the excitation threshold to 5000 eV by the BE-scaling method. The present oscillator strengths and cross sections supplement the fundamental molecular database of HBr and can be used for modeling in the semiconductor industry, astrophysics, and atmospheric chemistry.

A sonogram radiomics model for differentiating granulomatous lobular mastitis from invasive breast cancer: a multicenter study.

PURPOSE: To construct a nomogram based on sonogram features and radiomics features to differentiate granulomatous lobular mastitis (GLM) from invasive breast cancer (IBC). MATERIALS AND METHODS: A retrospective collection of 213 GLMs and 472 IBCs from three centers was divided into a training set, an internal validation set, and an external validation set. A radiomics model was built based on radiomics features, and the RAD score of the lesion was calculated. The sonogram radiomics model was constructed using ultrasound features and RAD scores. Finally, the diagnostic efficacy of the three sonographers with different levels of experience before and after combining the RAD score was assessed in the external validation set. RESULTS: The RAD score, lesion diameter, orientation, echogenicity, and tubular extension showed significant differences in GLM and IBC (p < 0.05). The sonogram radiomics model based on these factors achieved optimal performance, and its area under the curve (AUC) was 0.907, 0.872, and 0.888 in the training, internal, and external validation sets, respectively. The AUCs before and after combining the RAD scores were 0.714, 0.750, and 0.830 and 0.834, 0.853, and 0.878, respectively, for sonographers with different levels of experience. The diagnostic efficacy was comparable for all sonographers when combined with the RAD score (p > 0.05). CONCLUSION: Radiomics features effectively enhance the ability of sonographers to discriminate between GLM and IBC and reduce interobserver variation. The nomogram combining ultrasound features and radiomics features show promising diagnostic efficacy and can be used to identify GLM and IBC in a noninvasive approach.

Dissipation, residue, and dietary risk assessment of dimethachlon in grapes.

Dimethachlon, a dicarboximide fungicide, has gained widespread usage in Asian countries. While considered a low-toxicity fungicide, concerns regarding potential health effects, such as nephrotoxicity, have emerged. To date, neither China nor other countries have established maximum residue limit (MRL) for dimethachlon on grapes, and exposure risk assessment of dimethachlon is lacking. Here, we developed a QuEChERS method coupled with gas chromatography-mass spectrometry (GC-MS) to investigate the dissipation rates and terminal residues of dimethachlon in grapes, along with an assessment of dietary risk to consumers. Our results indicated that the average recoveries of dimethachlon in grapes ranged from 74 to 76%. The limit of quantification (LOQ) was 0.050 mg/kg. After undergoing 112 days of storage at -18 °C, the dissipation rate of dimethachlon in grapes was found to be less than 30%, suggesting a state of stable storage. In the context of good agricultural practice (GAP) guidelines, the half-lives of dimethachlon in grapes were 14.3-18.1 days, which is notably longer compared to the reported values for other crops. The terminal residues of dimethachlon in grapes at 14 and 21 days were found to be < 0.05-0.53 mg/kg and < 0.05-0.29 mg/kg, respectively. Regarding the dietary risk assessment, the calculated risk quotient (RQ) value was significantly below 100%, indicating a negligible chronic risk of dimethachlon in grapes at the recommended dosage. This study provides an important reference for the analysis of dimethachlon and offers valuable empirical data to support the establishment of MRL.