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Background: Rehospitalization is a quality-of-care indicator, yet little is known about its occurrence and predictors after myocardial infarction (MI) in the community.Objective: To examine 30-day rehospitalizations after incident MI.Design: Retrospective cohort study.Setting: Population-based registry in Olmsted County, Minnesota.Patients: 3010 patients who were hospitalized in Olmsted County with first-ever MI from 1987 to 2010 and survived to hospital discharge.Measurements: Diagnoses, therapies, and complications during incident and subsequent hospitalizations were identified. Manual chart review was performed to determine the cause of all rehospitalizations. The hazard ratios and cumulative incidence of 30-day rehospitalizations were determined by using Cox proportional hazards regression models.Results: Among 3010 patients (mean age, 67 years; 40.5% female) with incident MI (31.2% ST-segment elevation), 643 rehospitalizations occurred within 30 days in 561 (18.6%) patients. Overall, 30.2% of rehospitalizations were unrelated to the incident MI and 42.6% were related; the relationship was unclear in 27.2% of rehospitalizations. Angiography was performed in 153 (23.8%) rehospitalizations. Revascularization was performed in 103 (16.0%) rehospitalizations, of which 46 (44.7%) had no revascularization during the index hospitalization. After adjustment for potential confounders, diabetes, chronic obstructive pulmonary disease, anemia, higher Killip class, longer length of stay during the index hospitalization, and a complication of angiography or reperfusion or revascularization were associated with increased rehospitalization risk. The 30-day incidence of rehospitalization was 35.3% in patients who experienced a complication of angiography during the index MI hospitalization and 31.6% in those who experienced a complication of reperfusion or revascularization during the index MI hospitalization, compared with 16.8% in patients who had reperfusion or revascularization without complications.Limitation: This study represents the experiences of a single community.Conclusion: Comorbid conditions, longer length of stay, and complications of angiography and revascularization or reperfusion are associated with increased 30-day rehospitalization risk after MI. Many rehospitalizations seem to be unrelated to the incident MI.Primary Funding Source: National Institutes of Health. [ABSTRACT FROM AUTHOR]

In response to an apparent clustering of homicides at Fort Carson, Colorado, the U.S. Army Public Health Command (formerly the U.S. Army Center for Health Promotion and Preventive Medicine) Behavioral and Social Health Outcomes Program conducted a multidisciplinary epidemiologic consultation to identify factors contributing to violent behavior among soldiers at Fort Carson. This article summarizes the findings of the epidemiologic consultation report as provided to the Secretary of the Army and the Fort Carson Senior Mission Commander and released in its entirety publicly July 2009 and elaborates on the mixed-methods analytic approach used to study a complex behavioral issue at the community level. To aid in answering the key study questions, six study arms were designed and carried out: (1) index case analysis, (2) confinee interviews, (3) analysis of installation-level trends, (4) retrospective cohort analysis, (5) soldier focus groups and interviews, and (6) aggression risk factors survey. Although not conclusive, the findings suggest a combination of individual, unit, and environmental factors converged to increase the risk of violent behaviors, which made clustering of negative outcomes more likely. [ABSTRACT FROM AUTHOR]

Medical examiners and coroners (ME/Cs) are essential public health partners for terrorism preparedness and response. These medicolegal investigators support both public health and public safety functions and investigate deaths that are sudden, suspicious, violent, unattended, and unexplained. Medicolegal autopsies are essential for making organism-specific diagnoses in deaths caused by biologic terrorism. This report has been created to 1) help public health officials understand the role of ME/Cs in biologic terrorism surveillance and response efforts and 2) provide ME/Cs with the detailed information required to build capacity for biologic terrorism preparedness in a public health context. This report provides background information regarding biologic terrorism, possible biologic agents, and the consequent clinicopathologic diseases, autopsy procedures, and diagnostic tests as well as a description of biosafety risks and standards for autopsy precautions. ME/Cs' vital role in terrorism surveillance requires consistent standards for collecting, analyzing, and disseminating data. Familiarity with the operational, jurisdictional, and evidentiary concerns involving biologic terrorism-related death investigation is critical to both ME/Cs and public health authorities. Managing terrorism-associated fatalities can be expensive and can overwhelm the existing capacity of ME/Cs. This report describes federal resources for funding and reimbursement for ME/C preparedness and response activities and the limited support capacity of the federal Disaster Mortuary Operational Response Team. Standards for communication are critical in responding to any emergency situation. This report, which is a joint collaboration between CDC and the National Association of Medical Examiners (NAME), describes the relationship between ME/Cs and public health departments, emergency management agencies, emergency operations centers, and the Incident Command System. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To assess left ventricular (LV) function and brain-type natriuretic peptide (BNP) in patients with first-time flash pulmonary edema (FPE). PATIENTS AND METHODS: We retrospectively studied all patients presenting to Mayo Clinic's site in Rochester, MN, from January 5, 2000, to December 30, 2004, with FPE. Only patients with first-time FPE who had undergone BNP assessment and echocardiography within 24 hours of presentation were included. Patients were divided into 2 groups: those with reduced LV ejection fraction (LVEF) (less than 50%) and those with preserved LVEF (equals 50%). RESULTS: Thirty-seven patients met the inclusion criteria (22 female, 15 male). Mean plus or minus SD LVEF was 41% plus or minus 13%. The LVEF was reduced in 73% (group 1, n equals 27; mean plus or minus SD age, 75 plus or minus 8 years) and preserved in 27% (group 2, n equals 10; mean plus or munus SD age, 75 plus or minus 13 years). Most frequent underlying causes for first-time FPE were coronary artery disease and hypertension. Patients with preserved LVEF had significantly lower BNP levels at presentation (535 pg/mL [interquartile range, 352-1210 pg/mL]) vs 1320 pg/mL (interquartile range, 768-2000 pg/mL; P equals .01), despite similar elevated LV filling pressures as measured by echocardiography. The mean plus or minus SD ratio of early diastolic mitral valve inflow velocity to early diastolic mitral annulus velocity was 23 plus or minus 8 vs 22 plus or minus 10; P equals .78. Early diastolic mitral annulus velocity, a surrogate measurement for myocardial relaxation, was reduced in all patients with preserved LVEF and in 95% of patients with reduced LVEF. CONCLUSION: Coronary artery disease and hypertension are the most common precipitating factors for first-time FPE. Reduced myocardial relaxation in almost all patients regardless of LVEF supports the notion that diastolic dysfunction is a prerequisite for FPE. Levels of BNP were elevated in every patient regardless of LVEF but were significantly lower in patients with preserved LVEF despite similarly elevated LV filling pressures. [ABSTRACT FROM AUTHOR]

OBJECTIVES: To determine the clinical and angiographic characteristics of patients who underwent coronary artery bypass graft (CABG) surgery before the availability of drug-eluting stents (DES) and to project the potential impact of percutaneous coronary intervention using DES. PATIENTS AND METHODS: We reviewed the coronary angiograms obtained between March 1999 and December 2001 of 192 consecutive patients from Olmsted County, Minnesota, who had undergone isolated CABG surgery for the first time. Three interventional cardiologists categorized the patients into 1 of 4 groups on the basis of technical feasibility of complete revascularization by percutaneous coronary intervention with DES. RESULTS: The study population consisted primarily of men (78%), with a mean age of 67 years. Of the 192 patients, 58 (30%) had diabetes mellitus, and 124 (65%) had 3-vessel disease. Twelve patients (6%) had lesions suitable for stents that matched the inclusion criteria for DES in recently published trials; 77 (40%) had lesions suitable for stents but had lesion characteristics not included in the initial DES trials. Thirty-two patients (17%) had target lesions considered technically difficult, but feasible, for stent placement. Seventy-one patients (37%) had lesions unsuitable for percutaneous coronary intervention (75% of these due to chronic occlusions) with the current stent delivery technology. CONCLUSION: This population-based analysis suggests that only a small proportion of patients undergoing CABG surgery meets the strict angiographic eligibility criteria for DES on the basis of recent trials. However, up to 46% of current CABG patients may ultimately undergo conversion to DES. The remaining 54% of this patient population may still not be ideal candidates for DES with the current stent delivery technology. [ABSTRACT FROM AUTHOR]

Objective: To compare left ventricular (LV) systolic and diastolic function in patients with apical ballooning syndrome (ABS) and those with acute myocardial infarction (AMI) using 2-dimensional Doppler echocardiography and strain rate imaging (SRI).Patients and Methods: We prospectively enrolled patients with newly diagnosed AMI and ABS who had akinetic apical walls. Both 2-dimensional Doppler echocardiography and SRI were performed on hospital day 1 or within 24 hours of primary percutaneous coronary intervention.Results: Twenty-four patients with AMI and 13 patients with ABS (mean +/- SD age, 63+/-15 vs 73+/-12 years; P=.03) were prospectively enrolled in the study from October 3, 2005 through July 12, 2006. The mean +/- SD LV end-diastolic volume was larger (58.1+/-9.1 vs 45.2+/-10.6 mL/m(2); P<.001) and the mean +/- SD LV ejection fraction was lower (35%+/-6% vs 43%+/-9%; P=.006) in patients with ABS compared with patients with AMI. The early diastolic mitral annular velocity was similar (0.06+/-0.02 vs 0.06+/-0.02 m/s; P=.85) in both groups, but the ratio of early diastolic mitral valve inflow velocity to early diastolic mitral annulus velocity was higher in patients with AMI than in patients with ABS (16.3+/-6.9 vs 12.2+/-3.2; P=.05). The systolic strain rate was decreased at the apex in both groups (P=.98). Both the early diastolic strain rate of the apex (0.64+/-0.24 vs 0.48+/-0.30 s(-1); P=.04) and the postsystolic shortening index of the apex (61%+/-15% vs 45%+/-23%; P=.006) were higher in the patients with ABS than in those with AMI. However, early diastolic SR was higher in the akinetic apical walls of patients with AMI with recovery than those with no recovery (0.64+/-0.35 vs 0.43+/-0.25 s(-1); P=.04) and was similar between akinetic apical walls of patients with AMI with recovery and the akinetic apical walls of ABS.Conclusion: Compared with patients with AMI, those with ABS showed the functional paradox of worse initial LV systolic function with larger LV size but better LV diastolic function. The early systolic strain rate and postsystolic shortening were greater in patients with ABS than in those with AMI; hence, these measurements can be helpful in distinguishing ABS from AMI and in detecting myocardial viability. [ABSTRACT FROM AUTHOR]

Objectives: To determine the frequency of urgent coronary angiography in patients with acute pericarditis and to examine clinical characteristics associated with coronary angiography.Patients and Methods: This is a retrospective analysis of all incident cases of acute viral or idiopathic pericarditis evaluated at Mayo Clinic's site in Rochester, MN, between January 1, 2000, and December 31, 2006. The main outcome measures were use of urgent coronary angiography and rate of concomitant coronary artery disease in patients with pericarditis.Results: There were 238 patients with a final diagnosis of acute pericarditis (mean age, 47.7+/-17.9 years; 157 [66.0%] were male). On the initial electrocardiogram, 146 patients (61.3%) had ST-segment elevation, and 92 (38.7%) had no ST-segment elevation. Coronary angiography was performed in 40 patients (16.8% of all patients); the frequency was 5-fold higher among those with ST-segment elevation (24.7% vs 4.3%; P<.001). Additionally, 7 patients (4.8%) with ST-segment elevation received thrombolytics before transfer to our institution; no patients without ST-segment elevation received thrombolysis (P=.05). Characteristics associated with a higher likelihood of coronary angiography included typical anginal chest pain, ST-segment elevation, previous percutaneous coronary intervention, elevated troponin T values, diaphoresis, and male sex. Coronary angiography revealed concomitant mild to moderate coronary artery disease in 14 (35.0%) of the 40 patients who underwent this procedure.Conclusion: Urgent coronary angiography is commonly performed in patients with acute pericarditis, particularly those with ST-segment elevation, typical myocardial infarction symptoms, and elevated troponin T values. Coronary artery disease was present angiographically in one-third of patients undergoing the procedure. Although patients with ST-segment elevation myocardial infarction must receive prompt reperfusion, clinicians must also consider the diagnosis of pericarditis to avoid unneeded coronary angiography. [ABSTRACT FROM AUTHOR]

Objectives: Our aim was to examine whether gender-based differences in mortality after percutaneous coronary interventions (PCIs) have changed in the past 25 years.Background: Women with coronary artery disease have a higher risk of adverse outcomes after PCIs than do men. Recent temporal trends in short-term and long-term mortality in women after PCIs are unknown.Methods: We performed a retrospective cohort study of 18,885 consecutive, unique patients who underwent PCIs between 1979 and 1995 (early group, n = 7,904, 28% women) and between 1996 and 2004 (recent group, n = 10,981, 31% women). Thirty-day and long-term mortality were compared by gender.Results: Compared with men, women undergoing PCIs were older and more likely to have diabetes mellitus, hypertension, or hypercholesterolemia. Overall, PCI was successful in 89% of women and 90% of men. In the recent group, 30-day mortality was significantly reduced compared with that in the early group in women (2.9% vs. 4.4%, p = 0.002) and men (2.2% vs. 2.8%, p = 0.04). However, long-term survival was similar between the early and recent groups among both men and women. After adjustment for risk factors, there was no difference between men and women from 1994 onward for either 30-day or long-term outcomes.Conclusions: The 30-day mortality after PCI in men and women has decreased in the past 25 years. After accounting for baseline risks, no differences in short-term or long-term mortality were observed between men and women. [ABSTRACT FROM AUTHOR]

Objective: To compare outcomes among patients receiving eptifibatide or abciximab during primary percutaneous coronary intervention (PCI) for acute myocardial infarction (MI) with ST elevation or new left bundle branch block.Patients and Methods: From January 1999 through January 2004, 576 patients underwent primary PCI and received adjunctive glycoprotein IIb/IIIa receptor antagonists. Propensity scores were used to adjust for baseline differences between groups. Logistic regression and Cox proportional hazards were used to model the association between choice of glycoprotein IIlb/IIIa receptor antagonist and adverse events.Results: Abciximab was given to 327 patients (57%) and eptifibatide to 249 (43%). Observed rates of in-hospital death or MI did not differ between groups (eptifibatide, 6%; abciximab, 5%; P = .95). This result persisted with adjustment for various patient characteristics (adjusted odds ratio, 1.03; 95% confidence interval, 0.40-2.65; P = .95). Kaplan-Meier estimated rates of death, MI, or target vessel revascularization at 1-year follow-up were 20.9% with eptifibatide and 22.3% with abciximab. The adjusted hazard ratio for the composite end point during a median follow-up of 12 months was 1.36 (95% confidence interval, 0.89-2.07; P = -.16).Conclusion: In this observational analysis, outcomes were similar with use of either abciximab or eptifibatide among patients undergoing primary PCI for acute MI. Additional comparative research is warranted to confirm these results. [ABSTRACT FROM AUTHOR]

Objective: To test the feasibility and safety of genotype guidance in the selection of P2Y 12 monotherapy within 1 week of percutaneous coronary interventions (PCIs) among patients with high bleeding risk (HBR)., Patient and Methods: The study was a single-center, open-label, pilot trial. Patients (n=100) with HBR (as defined by an academic research consortium) after successful PCI received dual antiplatelet therapy with clopidogrel and aspirin. Following availability of cytochrome P450 2C19 (CYP2C19) genotype results (mean, 2.9 days), aspirin was discontinued. Normal, rapid, or ultrarapid CYP2C19 metabolizers continued clopidogrel monotherapy for 90 days whereas loss-of-function allele carriers switched to prasugrel or ticagrelor monotherapy. The primary safety endpoints were a composite of post-dismissal cardiac death/spontaneous myocardial infarction less than 30 days or stent thrombosis <90 days of discharge. The subjects also underwent post-dismissal assessment for BARC (Bleeding Academic Research Consortium) type 3 or 5 bleeding, all-cause death, any MI, and/or repeat revascularization up to 90 days., Results: There were 98 patients with complete data (median age, 76.5 years, 36% women; 49% acute coronary syndrome). Sixty-nine (70.4%) were normal, rapid, or ultrarapid metabolizers and continued clopidogrel monotherapy, and 29 (29.6%) were intermediate CYP2C19 metabolizers and received monotherapy with prasugrel (n=21) or ticagrelor (n=8). The mean duration of dual antiplatelet therapy was 5.1 days. During 90-day follow-up, no patient died, there was one possible stent thrombosis, and three patients on clopidogrel had Bleeding Academic Research Consortium type 3 bleeding events., Conclusion: Genotype-guided P2Y 12 inhibitor monotherapy within a week of PCI is feasible and likely safe in patients with HBR (CHAMP [Clopidogrel With High Bleeding Risk and Adverse Events With Monotherapy in Patients Undergoing Percutaneous Coronary Interventions]; NCT05223335)., (Copyright © 2024 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

Polychlorinated biphenyls are ubiquitous environmental contaminants linkedc with peripheral immune and neural dysfunction. Neuroimmune signaling is critical to brain development and later health; however, effects of PCBs on neuroimmune processes are largely undescribed. This study extends our previous work in neonatal or adolescent rats by investigating longer-term effects of perinatal PCB exposure on later neuroimmune responses to an inflammatory challenge in adulthood. Male and female Sprague-Dawley rats were exposed to a low-dose, environmentally relevant, mixture of PCBs (Aroclors 1242, 1248, and 1254, 1:1:1, 20 μg / kg dam BW per gestational day) or oil control during gestation and via lactation. Upon reaching adulthood, rats were given a mild inflammatory challenge with lipopolysaccharide (LPS, 50 μg / kg BW, ip) or saline control and then euthanized 3 hours later for gene expression analysis or 24 hours later for immunohistochemical labeling of Iba1+ microglia. PCB exposure did not alter gene expression or microglial morphology independently, but instead interacted with the LPS challenge in brain region- and sex-specific ways. In the female hypothalamus, PCB exposure blunted LPS responses of neuroimmune and neuromodulatory genes without changing microglial morphology. In the female prefrontal cortex, PCBs shifted Iba1+ cells from reactive to hyperramified morphology in response to LPS. Conversely, in the male hypothalamus, PCBs shifted cell phenotypes from hyperramified to reactive morphologies in response to LPS. The results highlight the potential for long-lasting effects of environmental contaminants that are differentially revealed over a lifetime, sometimes only after a secondary challenge. These neuroimmune endpoints are possible mechanisms for PCB effects on a range of neural dysfunction in adulthood, including mental health and neurodegenerative disorders. The findings suggest possible interactions with other environmental challenges that also influence neuroimmune systems., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Margaret Bell reports financial support was provided by National Institute of Environmental Health Sciences. Andrea Gore reports financial support was provided by National Institute of Environmental Health Sciences. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Purpose: Spatio-temporal variability in clinical fluoroscopy and cine angiography images combined with nonlinear image processing prevents the application of traditional image quality measurements in the cardiac catheterization laboratory. We aimed to develop and validate methods to measure human observer impressions of the image quality., Approach: Multi-frame images of the thorax of a euthanized pig were acquired to provide an anatomical background. The detector dose was varied from 6 to 200 nGy (increments 2×), and 0.6 and 1.0 mm focal spots were used. Two coronary stents with/without 0.5 mm separation and a synthetic right coronary artery (RCA) with hemispherical defects were embedded into the background images as test objects. The quantitative observer ( n = 17 ) performance was measured using a two-alternating forced-choice test of whether stents were separated and by a count of visible right coronary artery defects. Qualitative impressions of noise, spatial resolution, and overall image quality were measured using a visual analog scale (VAS). A paired t -test and multinomial logistic regression model were used to identify statistically significant factors affecting the observer's impression image quality., Results: The proportion of correct detection of stent separation and the number of reported right coronary artery defects changed significantly with detector dose increment in the 6 to 100 nGy ( p < 0.05 ). Although a trend favored the 0.6 versus 1.0 mm focal spot for these quantitative assessments, this was insignificant. Visual analog scale measurements changed significantly with detector dose increments in the range of 24 to 100 nGy and focal spot size ( p < 0.05 ). The application of multinomial logistic regression analysis to observer VAS scores demonstrated sensitivity matching of the paired t -test applied to quantitative observer performance measurements., Conclusions: Both quantitative and qualitative measurements of observer impression of the image quality were sensitive to image quality changes associated with changing the detector dose and focal spot size. These findings encourage future work that uses qualitative image quality measurements to assess clinical fluoroscopy and angiography image quality., (© 2024 Society of Photo-Optical Instrumentation Engineers (SPIE).)

Limited data exist regarding outcomes after coronary angiography (CAG) and percutaneous coronary intervention (PCI) in patients aged ≥90 years admitted to the cardiac intensive care unit (CICU) with acute coronary syndrome (ACS). We studied sequential CICU patients ≥90 years admitted with ACS from 2007 to 2018. Three therapeutic approaches were defined: (1) No CAG; (2) CAG without PCI (CAG/No PCI); and (3) CAG with PCI (CAG/PCI). In-hospital mortality was evaluated using multivariable logistic regression. All-cause 1-year mortality was evaluated using Kaplan-Meier and multivariable Cox proportional hazards analysis. The study included 239 patients with a median age of 92 (range 90 to 100) years (57% females; 45% ST-elevation myocardial infarction; 8% cardiac arrest; 16% shock). The No CAG group had higher Day 1 Sequential Organ Failure Assessment scores, more co-morbidities, worse kidney function, and fewer ST-elevation myocardial infarctions. In-hospital mortality was 20.8% overall and did not differ between the No CAG (n = 103; 21.4%), CAG/No PCI (n = 47; 21.3%), and CAG/PCI (n = 90; 20.0%) groups, before or after adjustment. Overall 1-year mortality was 52.5% and did not differ between groups before or after adjustment. Median survival was 6.9 months overall and 41.2% of hospital survivors died within 1 year of CICU admission. CICU patients aged ≥90 years with ACS have a substantial burden of illness with high in-hospital and 1-year mortality that was not lower in those who underwent CAG or PCI. These results suggest that careful patient selection for invasive coronary procedures is essential in this vulnerable population., Competing Interests: Declaration of competing interest The authors have no competing interests to declare., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objectives: Early coronary angiography (CAG) has been recommended in selected patients following out-of-hospital-cardiac-arrest (OHCA). We aimed to identify clinical features associated with acute coronary occlusion (ACO) and evaluate the associations between ACO, successful percutaneous coronary intervention (PCI) and outcomes in this population., Methods: We included comatose OHCA patients treated with targeted temperature management (TTM) between December 2005 and September 2016 who underwent early CAG within 24 hours. The co-primary outcomes were all-cause 30-day mortality and good neurological outcome (modified Rankin Score [mRS] ≤2) at hospital discharge., Results: Among 155 patients (93% shockable arrest rhythm, 55% with ST elevation), 133 (86%) had coronary artery stenosis ≥50% and 65 (42%) had ACO. ST elevation (sensitivity 74%, specificity 59%, OR 4.0, 95% CI 2.0-8.1) and elevated first troponin (sensitivity 88%, specificity 26%, OR 2.5, 95% CI 1.1-6.1) had limited sensitivity and specificity for ACO. Unadjusted 30-day mortality did not differ significantly by coronary disease severity or ACO. Successful PCI was associated with a lower risk of 30-day mortality (adjusted HR 0.5, 95% CI 0.2-0.9, P=.03), especially among patients with ACO (adjusted HR 0.4, 95% CI 0.1-0.9, P=0.03). After adjustment, ACO and PCI were not associated with the probability of good neurological outcome., Conclusions: In this select cohort of resuscitated OHCA patients undergoing CAG, unstable coronary disease is highly prevalent and successful PCI was associated with a higher probability of 30-day survival, especially among those with ACO. Neither ACO nor successful PCI were independently associated with good neurological outcome.

Background: Genetic-guided P2Y 12 inhibitor selection has been proposed to reduce ischemic events by identifying CYP2C19 loss-of-function (LOF) carriers at increased risk with clopidogrel treatment after percutaneous coronary intervention (PCI). A prespecified analysis of TAILOR-PCI (Tailored Antiplatelet Therapy Following PCI) evaluated the effect of genetic-guided P2Y 12 inhibitor therapy on cumulative ischemic and bleeding events., Objectives: Here, the authors detail a prespecified analysis of cumulative endpoints. The primary endpoint was cumulative incidence rate of ischemic events at 12 months. Cumulative incidence of major and minor bleeding was a secondary endpoint. Cox proportional hazards models as adapted by Wei, Lin, and Weissfeld were used to estimate the effect of this strategy on all observed events., Methods: The TAILOR-PCI trial was a prospective trial including 5,302 post-PCI patients with acute and stable coronary artery disease (CAD) who were randomized to genetic-guided P2Y 12 inhibitor or conventional clopidogrel therapy. In the genetic-guided group, LOF carriers were prescribed ticagrelor, whereas noncarriers received clopidogrel. TAILOR-PCI's primary analysis was time to first event in LOF carriers., Results: Among 5,276 patients (median age 62 years; 25% women; 82% acute CAD; 18% stable CAD), 1,849 were LOF carriers (903 genetic-guided; 946 conventional therapy). The cumulative primary endpoint was significantly reduced in the genetic-guided group compared with the conventional therapy (HR: 0.61; 95% CI: 0.41-0.89; P = 0.011) with no significant difference in cumulative incidence of major or minor bleeding (HR: 1.36; 95% CI: 0.67-2.76; P = 0.39)., Conclusions: Among CYP2C19 LOF carriers undergoing PCI, a genetic-guided strategy resulted in a statistically significant reduction in cumulative ischemic events without a significant difference in bleeding. (Tailored Antiplatelet Therapy Following PCI [TAILOR-PCI]; NCT01742117)., Competing Interests: Funding Support and Author Disclosures Funding for this research was provided by the National Institutes of Health (NIH) grants U01HL128606 to Drs Pereira and Farkouh and U01HL128626 to Dr Bailey. The content of this manuscript is solely the responsibility of the authors and does not necessarily reflect the views of the National Heart, Lung, and Blood Institute (NHLBI) or the National Institutes of Health. Dr Farkouh has received grants from NHLBI, Amgen, Novartis, and Novo Nordisk. Mr Lennon has received grants from the National Institutes of Health (NIH)/NHLBI and receiving nonfinancial support from Spartan Biosciences. Dr So has received grants from Eli Lilly Canada, Spartan Biosciences, Roche Diagnostics, and Aggredyne Inc; and has received personal fees from AstraZeneca Canada, Bayer Canada, and Servier Canada. Dr Goodman has received research grant support (eg, steering committee or data and safety monitoring committee) and/or speaker/consulting honoraria (eg, advisory boards) from Amgen, Anthos Therapeutics, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, CSL Behring, Daiichi Sankyo/American Regent, Eli Lilly, Esperion, Ferring Pharmaceuticals, HLS Therapeutics, JAMP Pharma, Merck, Novartis, Novo Nordisk A/C, Pendopharm/Pharmascience, Pfizer, Regeneron, Sanofi, Servier, Tolmar Pharmaceuticals, and Valeo Pharma; and has received salary support/honoraria from the Heart and Stroke Foundation of Ontario/University of Toronto (Polo) Chair, Canadian Heart Research Centre and MD Primer, Canadian VIGOUR Centre, Cleveland Clinic Coordinating Centre for Clinical Research, Duke Clinical Research Institute, New York University Clinical Coordinating Centre, PERFUSE Research Institute, and the TIMI Study Group (Brigham Health). Dr Lerman has received personal fees from Itamar Medical, Phillips/Volcano, Shahal, and Wei Jian RC Inc. Dr Tanguay has received personal fees from Mayo Clinic, AstraZeneca, Bayer, Daiichi Sankyo, Servier, Novartis, and BMS-Pfizer Alliance. Dr Welsh has received grants and/or personal fees from AstraZeneca, Pfizer, Bayer, Canadian Cardiac Society, Mayo Clinic, Boehringer Ingelheim, and Novartis. Dr Bailey has received grants from NIH. Dr Pereira has received grants from the NHLBI. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023. Published by Elsevier Inc.)

Despite numerous clinically available vaccines and therapeutics, aged patients remain at increased risk for COVID-19 morbidity. Furthermore, various patient populations, including the aged can have suboptimal responses to SARS-CoV-2 vaccine antigens. Here, we characterized vaccine-induced responses to SARS-CoV-2 synthetic DNA vaccine antigens in aged mice. Aged mice exhibited altered cellular responses, including decreased IFNγ secretion and increased TNFα and IL-4 secretion suggestive of T H 2-skewed responses. Aged mice exhibited decreased total binding and neutralizing antibodies in their serum but significantly increased T H 2-type antigen-specific IgG1 antibody compared to their young counterparts. Strategies to enhance vaccine-induced immune responses are important, especially in aged patient populations. We observed that co-immunization with plasmid-encoded adenosine deaminase (pADA)enhanced immune responses in young animals. Ageing is associated with decreases in ADA function and expression. Here, we report that co-immunization with pADA enhanced IFNγ secretion while decreasing TNFα and IL-4 secretion. pADA expanded the breadth and affinity SARS-CoV-2 spike-specific antibodies while supporting T H 1-type humoral responses in aged mice. scRNAseq analysis of aged lymph nodes revealed that pADA co-immunization supported a T H 1 gene profile and decreased FoxP3 gene expression. Upon challenge, pADA co-immunization decreased viral loads in aged mice. These data support the use of mice as a model for age-associated decreased vaccine immunogenicity and infection-mediated morbidity and mortality in the context of SARS-CoV-2 vaccines and provide support for the use of adenosine deaminase as a molecular adjuvant in immune-challenged populations., Competing Interests: DW has received grant funding, participates in industry collaborations, has received speaking honoraria, and has received fees for consulting, including serving on scientific review committees. Remunerations received by DW include direct payments and equity/options. DW also discloses the following associations with commercial partners: Geneos consultant/advisory board, AstraZeneca advisory board, speaker, Inovio board of directors, consultant, Sanofi advisory board, BBI advisory board, Pfizer advisory Board, Flagship consultant, and Advaccine consultant. SW is a scientific founder of Avamab Pharma Inc., a pre-clinical, pre-revenue stage company dedicated to research and development of AAV gene therapies for the treatment and prevention of infectious diseases. SW is a co-founder and Chief Scientific Officer of Inspire Biotherapeutics, a pre-clinical, pre-revenue stage gene therapy company developing AAV-based therapies for monogenic lung diseases. SW is an inventor on issued patents in Canada and US for the AAV6.2FF capsid, which are owned by the University of Guelph, and licensed to Avamab Pharma Inc., Inspire Biotherapeutics, and Cellastra Inc. From 2020 to February 2023, SW was an unpaid scientific advisor for Cellastra Inc., which is dedicated to research and development of gene therapies targeting root causes of scarring. SW is a co-inventor on a pending US and Canadian patent for the Engineered Newcastle disease virus vector and uses thereof, filed/owned by the University of Guelph. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Gary, Tursi, Warner, Cuismano, Connors, Parzych, Griffin, Bell, Ali, Frase, Hojecki, Canziani, Chaiken, Kannan, Moffat, Embury-Hyatt, Wooton, Kossenkov, Patel, Kobasa, Kutzler, Haddad and Weiner.)

Herein, we studied the impact of empty LNP (eLNP), component of mRNA-based vaccine, on anti-viral pathways and immune function of cells from young and aged individuals. eLNP induced maturation of monocyte derived dendritic cells (MDDCs). We further show that eLNP upregulated CD40 and induced cytokine production in multiple DC subsets and monocytes. This coincided with phosphorylation of TANK binding kinase 1 (pTBK1) and interferon response factor 7 (pIRF7). In response to eLNP, healthy older adults (>65 yrs) have decreased CD40 expression, and IFN-γ output compared to young adults (<65 yrs). Additionally, cells from older adults have a dysregulated anti-viral signaling response to eLNP stimulation, measured by the defect in type I IFN production, and phagocytosis. Overall, our data show function of eLNP in eliciting DC maturation and innate immune signaling pathways that is impaired in older adults resulting in lower immune responses to SARS-CoV-2 mRNA-based vaccines., (© 2023. The Author(s).)

Although concussions are a popular focus of neurotrauma research, subconcussions occur with higher frequency but are less well-studied. A subconcussion is an impact to the head that does not result in immediately diagnosable concussion but can result in later neurological consequences. Repeat subconcussions can produce behavioral impairments and neuropathology that is similar to or worse than those seen following a single concussion. The current study modified a previously established closed head injury model of concussion to create a subconcussion model and examines sex differences in behavioral responses to repeated subconcussion in the adult rat. Rats received a single concussion, single or repeat subconcussions, or no impact and behavior was monitored from 2 h through 31 days post-injury. A single concussion or repeat subconcussion resulted in deficits in locomotion, righting reflexes, and recognition memory. The degree of deficit induced by repeat subconcussions were either similar (righting reflexes) or greater/more persistent (locomotor deficits and recognition memory) than that of a concussion. Single subconcussion resulted in acute deficits that were mild and limited to righting reflexes and locomotion. Sex differences were observed in responses to repeat subconcussion: females showed greater deficits in righting reflexes, locomotion, and vestibular function, while males showed greater alterations in anxiety and depressive-like behavior. This study established a model of subconcussive impact where a single subconcussive impact resulted in minimal behavioral deficits but repeat subconcussions resulted in deficits similar to or worse than a single concussion. Our data also suggest sex differences in behavioral responses to both concussive and subconcussive impacts., Competing Interests: Competing Interests None to report., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Aminophylline, an adenosine antagonist, can be used to prevent adenosine-mediated bradyarrhythmias., Methods: Retrospective, observational, descriptive analysis of patients undergoing rotational atherectomy with intravenous (IV) aminophylline pretreatment during a 10-year period (2010-2020). The primary composite outcome was the occurrence of a documented bradyarrhythmia requiring pharmacologic intervention and/or temporary pacemaker (TPM) implantation., Results: A total of 296 patients received IV aminophylline pretreatment. The primary composite outcome occurred in 1.7% (n = 5) of patients. None of the patients required rescue TPM. Bradyarrhythmias were documented in 2.4% (n = 7) of patients. Pharmacologic interventions, typically with IV atropine, were used in 15% (n = 43) of patients. Per-vessel analyses demonstrated that patients undergoing atherectomy to the circumflex and right coronary arteries were more likely than those undergoing atherectomy to other vessels to have bradyarrhythmias requiring pharmacologic intervention (3.4% vs 0%, P = .01)., Conclusions: In this 10-year single-center experience using IV aminophylline pretreatment to prevent major bradyarrhythmias in patients undergoing coronary atherectomy, none of the patients required rescue TPM implantation. These data demonstrate that coronary atherectomy can be performed safely without prophylactic TPM, with aminophylline pretreatment and selective use of atropine representing an effective noninvasive approach., (© 2023 The Authors.)

Introduction: Healthcare organizations faced unique operational challenges during the COVID-19 pandemic. Assuring the safety of both patients and healthcare workers in hospitals has been the primary focus during the COVID-19 pandemic., Methods: The NIH Vaccine Program (VP) with the Vaccine Management System (VMS) was created based on the commitment of NIH leadership, program leadership, the development team, and the program team; defining Key Performance Indicators (KPIs) of the VP and the VMS; and the NIH Clinical Center's (NIH CC) interdisciplinary approach to deploying the VMS., Results: This article discusses the NIH business requirements of the VP and VMS, the target KPIs of the VP and the VMS, and the NIH CC interdisciplinary approach to deploying an organizational VMS for vaccinating the NIH workforce. The use of the DCRI Spiral-Agile Software Development Life Cycle enabled the development of a system with stakeholder involvement that could quickly adapt to changing requirements meeting the defined KPIs for the program and system. The assessment of the defined KPIs through a survey and comments from the survey support that the VP and VMS were successful., Conclusion: A comprehensive program to maintain a healthy workforce includes asymptomatic COVID testing, symptomatic COVID testing, contact tracing, vaccinations, and policy-driven education. The need to develop systems during the pandemic resulted in changes to build software quickly with the input of many more users and stakeholders then typical in a decreased amount of time., Competing Interests: No competing financial interests exist., (Copyright 2022, ABSA International 2022.)

The progressive impairment of immunity to pathogens and vaccines with aging is a significant public health problem as the world population shifts to an increased percentage of older adults (> 65). We have previously demonstrated that cells obtained from older volunteers have delayed and defective induction of type I interferons and T cell and B cell helper cytokines in response to TLR ligands when compared to those from adult subjects. However, the underlying intracellular mechanisms are not well described. Herein, we studied two critical pathways important in the production of type I interferon (IFN), the interferon response factor 7 (pIRF7), and TANK-binding kinase (pTBK-1). We show a decrease in pIRF7 and pTBK-1 in cross-priming dendritic cells (cDC1s), CD4 + T cell priming DCs (cDC2s), and CD14 dim CD16 + vascular patrolling monocytes from older adults (n = 11) following stimulation with pathway-specific agonists in comparison with young individuals (n = 11). The decrease in these key antiviral pathway proteins correlates with decreased phagocytosis, suggesting impaired function in Overall, our findings describe molecular mechanisms which explain the innate functional impairment in older adults and thus could inform us of novel approaches to restore these defects., (© 2022. The Author(s).)

Although severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines have demonstrated strong immunogenicity and protection against severe disease, concerns about the duration and breadth of these responses remain. In this study, we show that codelivery of plasmid-encoded adenosine deaminase-1 (pADA) with SARS-CoV-2 spike glycoprotein DNA enhances immune memory and durability in vivo. Coimmunized mice displayed increased spike-specific IgG of higher affinity and neutralizing capacity as compared with plasmid-encoded spike-only-immunized animals. Importantly, pADA significantly improved the longevity of these enhanced responses in vivo. This coincided with durable increases in frequencies of plasmablasts, receptor-binding domain-specific memory B cells, and SARS-CoV-2-specific T follicular helper cells. Increased spike-specific T cell polyfunctionality was also observed. Notably, animals coimmunized with pADA had significantly reduced viral loads compared with their nonadjuvanted counterparts in a SARS-CoV-2 infection model. These data suggest that pADA enhances immune memory and durability and supports further translational studies., (Copyright © 2022 by The American Association of Immunologists, Inc.)

Background: Previous percutaneous coronary intervention risk models were focused on single outcome, such as mortality or bleeding, etc, limiting their applicability. Our objective was to develop contemporary percutaneous coronary intervention risk models that not only determine in-hospital mortality but also predict postprocedure bleeding, acute kidney injury, and stroke from a common set of variables., Methods: We built risk models using logistic regression from first percutaneous coronary intervention for any indication per patient (n=19 322, 70.6% with acute coronary syndrome) using the Mayo Clinic registry from January 1, 2000 to December 31, 2016. Approval for the current study was obtained from the Mayo Foundation Institutional Review Board. Patients with missing outcomes (n=4183) and those under 18 (n=10) were removed resulting in a sample of 15 129. We built both models that included procedural and angiographic variables (Models A) and precatheterization model (Models B)., Results: Death, bleeding, acute kidney injury, and stroke occurred in 247 (1.6%), 650 (4.3%), 1184 (7.8%), and 67 (0.4%), respectively. The C statistics from the test dataset for models A were 0.92, 0.70, 0.77, and 0.71 and for models B were 0.90, 0.67, 0.76, and 0.71 for in-hospital death, bleeding, acute kidney injury, and stroke, respectively. Bootstrap analysis indicated that the models were not overfit to the available dataset. The probabilities estimated from the models matched the observed data well, as indicated by the calibration curves. The models were robust across many subgroups, including women, elderly, acute coronary syndrome, cardiogenic shock, and diabetes., Conclusions: The new risk scoring models based on precatheterization variables and models including procedural and angiographic variables accurately predict in-hospital mortality, bleeding, acute kidney injury, and stroke. The ease of its application will provide useful prognostic and therapeutic information to both patients and physicians.

Background: There are limited data on uninsured patients presenting with acute myocardial infarction-cardiogenic shock (AMI-CS). This study sought to compare the management and outcomes of AMI-CS between uninsured and privately insured individuals., Methods: Using the National Inpatient Sample (2000-2016), a retrospective cohort of adult (≥18 years) uninsured admissions (primary payer-self-pay or no charge) were compared with privately insured individuals. Interhospital transfers were excluded. Outcomes of interest included in-hospital mortality, temporal trends in admissions, use of cardiac procedures, do-not-resuscitate status, palliative care referrals, and resource utilization., Results: Of 402 182 AMI-CS admissions, 21 966 (5.4%) and 93 814 (23.3%) were uninsured and privately insured. Compared with private insured individuals, uninsured admissions were younger, male, from a lower socioeconomic status, had lower comorbidity, higher rates of acute organ failure, ST-segment elevation AMI-CS (77.3% versus 76.4%), and concomitant cardiac arrest (33.8% versus 31.9%; all P <0.001). Compared with 2000, in 2016, there were more uninsured (adjusted odds ratio, 1.15 [95% CI, 1.13-1.17]; P <0.001) and less privately insured admissions (adjusted odds ratio, 0.85 [95% CI, 0.83-0.87]; P <0.001). Uninsured individuals received less frequent coronary angiography (79.5% versus 81.0%), percutaneous coronary intervention (60.8% versus 62.2%), mechanical circulatory support (54% versus 55.5%), and had higher palliative care (3.8% versus 3.2%) and do-not-resuscitate status use (4.4% versus 3.2%; all P <0.001). Uninsured admissions had higher in-hospital mortality (adjusted odds ratio, 1.62 [95% CI, 1.55-1.68]; P <0.001) and resource utilization., Conclusions: Uninsured individuals have higher in-hospital mortality and lower use of guideline-directed therapies in AMI-CS compared with privately insured individuals.

Cardiac arrest (CA) is common and has been associated with adverse outcomes in patients with cardiogenic shock (CS). We sought to determine the prevalence, patient characteristics, and outcomes of CA in cardiovascular intensive care unit patients with CS. We queried cardiovascular intensive care unit admissions from 2007 to 2018 with an admission diagnosis of CS and compared patients with and without CA. Temporal trends were assessed using linear regression. The primary and secondary outcomes of in-hospital and 1-year mortality were analyzed using logistic regression and Cox proportional-hazards analysis, respectively. We included 1,498 patients, and CA was present in 510 patients (34%), with 258 (50.6% of patients with CA) having ventricular fibrillation (VF). Mean age was 68 ± 14 years, and 37% were females. The prevalence of CA decreased over time (from 43% in 2007 to 24% in 2018, p <0.001). Hospital mortality was 33.3% and decreased over time in patients without CA (from 30% in 2007 to 22% in 2018, p = 0.05), but not in patients with CA (p = 0.71). CA was associated with a higher risk of hospital mortality (51.0% vs 24.2%, adjusted odds ratio 2.15, 95% confidence interval [CI] 1.52 to 3.05, p <0.001), with no difference between VF CA and non-VF CA (p = 0.64). CA was associated with higher 1-year mortality (adjusted hazard ratio 1.53, 95% CI 1.24 to 1.89, p <0.001). In conclusion, CA is present in 1 of 3 of CS hospitalizations and confers a substantially higher risk of hospital and 1-year mortality with no improvement during our 12-year study period contrary to prevailing trends., Competing Interests: Disclosures The authors have no conflicts of interest to declare., (Copyright © 2022 Elsevier Inc. All rights reserved.)

A one-pot strategy for functionalizing pyranoside 1,2- cis -diols with two different ester protecting groups is reported. The approach employs regioselective acylation via orthoester hydrolysis promoted by a carboxylic acid, e.g., levulinic acid, acetic acid, benzoic acid, or chloroacetic acid. Upon removal of water and introduction of a coupling agent, the carboxylic acid is esterified to the hydroxyl group liberated during hydrolysis. Although applied to 1,2- cis -diols on pyranoside scaffolds, the method should be applicable to such motifs on any six-membered ring.

Vaccination is the most effective measure to protect against infections. However, with increasing age, there is a progressive decline in the ability of the immune system to both protect against infection and develop protective immunity from vaccination. This age-related decline of the immune system is due to age-related changes in both the innate and adaptive immune systems. With an aging world population and increased risk of pandemics, there is a need to continue to develop strategies to increase vaccine responses in the elderly. Here, the major age-related changes that occur in both the innate and adaptive immune responses that impair the response to vaccination in the elderly will be highlighted. Existing and future strategies to improve vaccine efficacy in the elderly will then be discussed, including adjuvants, delivery methods, and formulation. These strategies provide mechanisms to improve the efficacy of existing vaccines and develop novel vaccines for the elderly., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: There are limited data on the temporal trends, incidence, and outcomes of ST-segment-elevation myocardial infarction-cardiogenic shock (STEMI-CS)., Methods: Adult (>18 years) STEMI-CS admissions were identified using the National Inpatient Sample (2000-2017) and classified by tertiles of admission year (2000-2005, 2006-2011, 2012-2017). Outcomes of interest included temporal trends, acute organ failure, cardiac procedures, in-hospital mortality, hospitalization costs, and length of stay., Results: In ∼4.3 million STEMI admissions, CS was noted in 368,820 (8.5%). STEMI-CS incidence increased from 5.8% in 2000 to 13.0% in 2017 (patient and hospital characteristics adjusted odds ratio [aOR] 2.45 [95% confidence interval {CI} 2.40-2.49]; P < 0.001). Multiorgan failure increased from 55.5% (2000-2005) to 74.3% (2012-2017). Between 2000 and 2017, coronary angiography and percutaneous coronary intervention use increased from 58.8% to 80.1% and 38.6% to 70.6%, whereas coronary artery bypass grafting decreased from 14.9% to 10.4% (all P < 0.001). Over the study period, the use of intra-aortic balloon pump (40.6%-37.6%) decreased, and both percutaneous left ventricular assist devices (0%-12.9%) and extra-corporeal membrane oxygenation (0%-2.8%) increased (all P < 0.001). In hospital mortality decreased from 49.6% in 2000 to 32.7% in 2017 (aOR 0.29 [95% CI 0.28-0.31]; P < 0.001). During the 18-year period, hospital lengths of stay decreased, hospitalization costs increased and use of durable left ventricular assist device /cardiac transplantation remained stable (P > 0.05)., Conclusions: In the United States, incidence of CS in STEMI has increased 2.5-fold between 2000 and 2017, while in-hospital mortality has decreased during the study period. Use of coronary angiography and PCI increased during the study period., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 by the Shock Society.)

Background: Coronary endothelial dysfunction (CED) causes angina/ischemia in patients with nonobstructive coronary artery disease (NOCAD). Patients with CED have decreased number and function of CD34+ cells involved in normal vascular repair with microcirculatory regenerative potential and paracrine anti-inflammatory effects. We evaluated safety and potential efficacy of intracoronary autologous CD34+ cell therapy for CED., Methods: Twenty NOCAD patients with invasively diagnosed CED and persistent angina despite maximally tolerated medical therapy underwent baseline exercise stress test, GCSF (granulocyte colony stimulating factor)-mediated CD34+ cell mobilization, leukapheresis, and selective 1×10 5 CD34+ cells/kg infusion into left anterior descending. Invasive CED evaluation and exercise stress test were repeated 6 months after cell infusion. Primary end points were safety and effect of intracoronary autologous CD34+ cell therapy on CED at 6 months of follow-up. Secondary end points were change in Canadian Cardiovascular Society angina class, as-needed sublingual nitroglycerin use/day, Seattle Angina Questionnaire scores, and exercise time at 6 months. Change in CED was compared with that of 51 historic control NOCAD patients treated with maximally tolerated medical therapy alone., Results: Mean age was 52±13 years; 75% were women. No death, myocardial infarction, or stroke occurred. Intracoronary CD34+ cell infusion improved microvascular CED (%acetylcholine-mediated coronary blood flow increased from 7.2 [-18.0 to 32.4] to 57.6 [16.3-98.3]%; P =0.014), decreased Canadian Cardiovascular Society angina class (3.7±0.5 to 1.7±0.9, Wilcoxon signed-rank test, P =0.00018), and sublingual nitroglycerin use/day (1 [0.4-3.5] to 0 [0-1], Wilcoxon signed-rank test, P =0.00047), and improved all Seattle Angina Questionnaire scores with no significant change in exercise time at 6 months of follow-up. Historic control patients had no significant change in CED., Conclusions: A single intracoronary autologous CD34+ cell infusion was safe and may potentially be an effective disease-modifying therapy for microvascular CED in humans. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03471611.

Objective: To study associations between the Minnesota coronavirus disease 2019 (COVID-19) mitigation strategies on incidence rates of acute myocardial infarction (MI) or revascularization among residents of Southeast Minnesota., Methods: Using the Rochester Epidemiology Project, all adult residents of a nine-county region of Southeast Minnesota who had an incident MI or revascularization between January 1, 2015, and December 31, 2020, were identified. Events were defined as primary in-patient diagnosis of MI or undergoing revascularization. We estimated age- and sex-standardized incidence rates and incidence rate ratios (IRRs) stratified by key factors, comparing 2020 to 2015-2019. We also calculated IRRs by periods corresponding to Minnesota's COVID-19 mitigation timeline: "Pre-lockdown" (January 1-March 11, 2020), "First lockdown" (March 12-May 31, 2020), "Between lockdowns" (June 1-November 20, 2020), and "Second lockdown" (November 21-December 31, 2020)., Results: The incidence rate in 2020 was 32% lower than in 2015-2019 (24 vs 36 events/100,000 person-months; IRR, 0.68; 95% CI, 0.62-0.74). Incidence rates were lower in 2020 versus 2015-2019 during the first lockdown (IRR, 0.54; 95% CI, 0.44-0.66), in between lockdowns (IRR, 0.70; 95% CI, 0.61-0.79), and during the second lockdown (IRR, 0.54; 95% CI, 0.41-0.72). April had the lowest IRR (IRR 0.48; 95% CI, 0.34-0.68), followed by August (IRR, 0.55; 95% CI, 0.40-0.76) and December (IRR, 0.56; 95% CI, 0.41-0.77). Similar declines were observed across sex and all age groups, and in both urban and rural residents., Conclusion: Mitigation measures for COVID-19 were associated with a reduction in hospitalizations for acute MI and revascularization in Southeast Minnesota. The reduction was most pronounced during the lockdown periods but persisted between lockdowns., (© 2021 The Authors.)

Objective: To evaluate the epidemiology and outcomes of non-ST-segment-elevation myocardial infarction-cardiogenic shock (NSTEMI-CS) in the United States., Methods: Adult (>18 years) NSTEMI-CS admissions were identified using the National Inpatient Sample (2000-2017) and classified by tertiles of admission year (2000-2005, 2006-2011 and 2012-2017). Outcomes of interest included temporal trends of prevalence and in-hospital mortality, use of cardiac procedures, in-hospital mortality, hospitalization costs, and length of stay., Results: In over 7.3 million NSTEMI admissions, CS was noted in 189,155 (2.6%). NSTEMI-CS increased from 1.5% in 2000 to 3.6% in 2017 (adjusted odds ratio 2.03 [95% confidence interval 1.97-2.09]; P < .001). Rates of non-cardiac organ failure and cardiac arrest increased during the study period. Between 2000 and 2017, coronary angiography (43.9%-63.9%), early coronary angiography (13.6%-25.6%), percutaneous coronary intervention (14.8%-31.6%), and coronary artery bypass grafting use (19.0%-25.8%) increased (P < .001). Over the study period, the use of intra-aortic balloon pump remained stable (28.6%-28.8%), and both percutaneous left ventricular assist devices (0%-9.1%) and extra-corporeal membrane oxygenation (0.1%-1.6%) increased (all P < .001). In hospital mortality decreased from 50.2% in 2000 to 32.3% in 2017 (adjusted odds ratio 0.27 [95% confidence interval 0.25-0.29]; P < .001). During the 18-year period, hospital lengths of stay decreased, and hospitalization costs increased., Conclusions: In the United States, prevalence of CS in NSTEMI has increased 2-fold between 2000 and 2017, while in-hospital mortality has decreased during the study period. Use of coronary angiography and percutaneous coronary intervention increased during the study period., (Copyright © 2021 Elsevier Inc. All rights reserved.)

We introduce a new chamfering paradigm, locally connecting pixels to produce path distances that approximate Euclidean space by building a small network (a replacement product) inside each pixel. These " RE -grid graphs" maintain near-Euclidean polygonal distance contours even in noisy data sets, making them useful tools for approximation when exact numerical solutions are unobtainable or impractical. The RE -grid graph creates a modular global architecture with lower pixel-to-pixel valency and simplified topology at the cost of increased computational complexity due to its internal structure. We present an introduction to chamfering replacement products with a number of case study examples to demonstrate the potential of these graphs for path-finding in high frequency and low resolution image spaces which motivate further study. Possible future applications include morphology, watershed segmentation, halftoning, neural network design, anisotropic image processing, image skeletonization, dendritic shaping, and cellular automata.

Objective: To analyze outcomes of patients with ST-segment elevation myocardial infarction (STEMI) after successful primary percutaneous coronary intervention (PCI) triaged to the cardiac intensive care unit (CICU) vs a general telemetry unit by a Zwolle risk score-based algorithm., Methods: We introduced a quality improvement protocol in 2014 encouraging admission of STEMI patients with Zwolle score of 3 or less to general telemetry units unless they were hemodynamically unstable. We subsequently conducted a retrospective single-center cohort study of consecutive STEMI patients who had undergone primary PCI from January 1, 2014, to December 31, 2018. Outcomes studied include immediate complications, need for urgent unplanned intervention, need for CICU care, length of hospitalization, and survival., Results: We identified 547 patients, 406 with a Zwolle score of 3 or less. Of these, 192 (47.3%) were admitted to general telemetry and 214 (52.7%) to the CICU. Reasons for CICU admission included persistent chest pain, late presentation, and procedural complications. The average hospital length of stay was 2.1±1.4 days for non-CICU patients and 3.3±2.8 days for low-risk CICU patients ( P <.001). Two patients initially admitted to general telemetry required transfer to the CICU. There were 26 patients who required unplanned cardiovascular intervention within 30 days, 5 from the general telemetry unit; 540 patients survived to discharge. One in-hospital death occurred among those initially triaged to the general telemetry unit, and this was due to a noncardiac cause., Conclusion: A Zwolle score-based algorithm can be used to safely triage post-PCI STEMI patients to a general telemetry unit.

Objective: To determine whether the Mayo Cardiac Intensive Care Unit (CICU) Admission Risk Score (M-CARS) is associated with CICU resource utilization., Patients and Methods: Adult patients admitted to our CICU from 2007 to 2018 were retrospectively reviewed, and M-CARS was calculated from admission data. Groups were compared using Wilcoxon test for continuous variables and χ 2 test for categorical variables., Results: We included 12,428 patients with a mean age of 67±15 years (37% female patients). The mean M-CARS was 2.1±2.1, including 5890 (47.4%) patients with M-CARS less than 2 and 644 (5.2%) patients with M-CARS greater than 6. Critical care restricted therapies were frequently used, including mechanical ventilation in 28.0%, vasoactive medications in 25.5%, and dialysis in 4.8%. A higher M-CARS was associated with greater use of critical-care therapies and longer CICU and hospital length of stay. The low-risk cohort with M-CARS less than 2 was less likely to require critical-care-restricted therapies, including invasive or noninvasive mechanical ventilation (8.0% vs 46.1%), vasoactive medications (10.1% vs 38.8%), or dialysis (1.0% vs 8.2%), compared with patients with M-CARS greater than or equal to 2 (all P <.001)., Conclusion: Patients with M-CARS less than 2 infrequently require critical-care resources and have extremely low mortality, suggesting that the M-CARS could be used to facilitate the triage of critically ill cardiac patients., (© 2021 THE AUTHORS.)

Objective: To determine whether the Mayo Cardiac Intensive Care Unit (CICU) Admission Risk Score (M-CARS) accurately predicts 1-year mortality., Methods: We retrospectively reviewed adult CICU patients admitted from January 1, 2007, through April 30, 2018, and calculated M-CARS using admission data. We examined the association between admission M-CARS, as continuous and categorical variables, and 1-year mortality., Results: This study included 12,428 unique patients with a mean age of 67.6±15.2 years (4686 [37.7%] female). A total of 2839 patients (22.8%) died within 1 year of admission, including 1149 (9.2%) hospital deaths and 1690 (15.0%) of the 11,279 hospital survivors. The 1-year survival decreased incrementally as a function of increasing M-CARS (P<.001), and all components of M-CARS were significant predictors of 1-year mortality (P<.001). The 1-year survival among hospital survivors decreased incrementally as a function of increasing M-CARS for scores below 3 (all P<.001); however, there was no further decrease in 1-year survival for hospital survivors with M-CARS of 3 or more (P=.99). The M-CARS components associated with 1-year mortality among hospital survivors included blood urea nitrogen, red blood cell distribution width, Braden skin score, and respiratory failure (all P<.001)., Conclusion: M-CARS predicted 1-year mortality among CICU admissions, with a plateau effect at high M-CARS of 3 or more for hospital survivors. Significant added predictors of 1-year mortality among hospital survivors included markers of frailty and chronic illness., (Copyright © 2021 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

Aims: Cardiogenic shock (CS) is associated with poor outcomes in older patients, but it remains unclear if this is due to higher shock severity. We sought to determine the associations between age and shock severity on mortality among patients with CS., Methods and Results: Patients with a diagnosis of CS from Mayo Clinic (2007-15) and University Clinic Hamburg (2009-17) were subdivided by age. Shock severity was graded using the Society for Cardiovascular Angiography and Intervention (SCAI) shock stages. Predictors of 30-day survival were determined using Cox proportional-hazards analysis. We included 1749 patients (934 from Mayo Clinic and 815 from University Clinic Hamburg), with a mean age of 67.6 ± 14.6 years, including 33.6% females. Acute coronary syndrome was the cause of CS in 54.0%. The distribution of SCAI shock stages was 24.1%; C, 28.0%; D, 33.2%; and E, 14.8%. Older patients had similar overall shock severity, more co-morbidities, worse kidney function, and decreased use of mechanical circulatory support compared to younger patients. Overall 30-day survival was 53.3% and progressively decreased as age or SCAI shock stage increased, with a clear gradient towards lower 30-day survival as a function of increasing age and SCAI shock stage. Progressively older age groups had incrementally lower adjusted 30-day survival than patients aged <50 years., Conclusion: Older patients with CS have lower short-term survival, despite similar shock severity, with a high risk of death in older patients with more severe shock. Further research is needed to determine the optimal treatment strategies for older CS patients., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: journals.permissions@oup.com.)

Background There are limited contemporary data on the use of emergent coronary artery bypass grafting (CABG) in acute myocardial infarction. Methods and Results Adult (aged >18 years) acute myocardial infarction admissions were identified using the National (Nationwide) Inpatient Sample (2000-2017) and classified by tertiles of admission year. Outcomes of interest included temporal trends of CABG use; age-, sex-, and race-stratified trends in CABG use; in-hospital mortality; hospitalization costs; and hospital length of stay. Of the 11 622 528 acute myocardial infarction admissions, emergent CABG was performed in 1 071 156 (9.2%). CABG utilization decreased overall (10.5% [2000] to 8.7% [2017]; adjusted odds ratio [OR], 0.98 [95% CI, 0.98-0.98]; P <0.001), in ST-segment-elevation myocardial infarction (10.2% [2000] to 5.2% [2017]; adjusted OR, 0.95 [95% CI, 0.95-0.95]; P <0.001) and non-ST-segment-elevation myocardial infarction (10.8% [2000] to 10.0% [2017]; adjusted OR, 0.99 [95% CI, 0.99-0.99]; P <0.001), with consistent age, sex, and race trends. In 2012 to 2017, compared with 2000 to 2005, admissions receiving emergent CABG were more likely to have non-ST-segment-elevation myocardial infarction (80.5% versus 56.1%), higher rates of noncardiac multiorgan failure (26.1% versus 8.4%), cardiogenic shock (11.5% versus 6.4%), and use of mechanical circulatory support (19.8% versus 18.7%). In-hospital mortality in CABG admissions decreased from 5.3% (2000) to 3.6% (2017) (adjusted OR, 0.89; 95% CI, 0.88-0.89 [ P <0.001]) in the overall cohort, with similar temporal trends in patients with ST-segment-elevation myocardial infarction and non-ST-segment-elevation myocardial infarction. An increase in lengths of hospital stay and hospitalization costs was seen over time. Conclusions Utilization of CABG has decreased substantially in acute myocardial infarction admissions, especially in patients with ST-segment-elevation myocardial infarction. Despite an increase in acuity and multiorgan failure, in-hospital mortality consistently decreased in this population.

The central dogma of biology does not allow for the study of glycans using DNA sequencing. We report a liquid glycan array (LiGA) platform comprising a library of DNA 'barcoded' M13 virions that display 30-1,500 copies of glycans per phage. A LiGA is synthesized by acylation of the phage pVIII protein with a dibenzocyclooctyne, followed by ligation of azido-modified glycans. Pulldown of the LiGA with lectins followed by deep sequencing of the barcodes in the bound phage decodes the optimal structure and density of the recognized glycans. The LiGA is target agnostic and can measure the glycan-binding profile of lectins, such as CD22, on cells in vitro and immune cells in a live mouse. From a mixture of multivalent glycan probes, LiGAs identify the glycoconjugates with optimal avidity necessary for binding to lectins on living cells in vitro and in vivo.