High Events Research Articles

Temporal Association Among Influenza-Like Illness, Cardiovascular Events, and Vaccine Dose in Patients With High-Risk Cardiovascular Disease

Influenza-like illness (ILI) activity has been associated with increased risk of cardiopulmonary (CP) events during the influenza season. High-dose trivalent influenza vaccine was not superior to standard-dose quadrivalent vaccine for reducing these events in patients with high-risk cardiovascular (CV) disease in the Influenza Vaccine to Effectively Stop Cardio Thoracic Events and Decompensated Heart Failure (INVESTED) trial. To evaluate whether high-dose trivalent influenza vaccination is associated with benefit over standard-dose quadrivalent vaccination in reducing CP events during periods of high, local influenza activity. This study was a prespecified secondary analysis of INVESTED, a multicenter, double-blind, active comparator randomized clinical trial conducted over 3 consecutive influenza seasons from September 2016 to July 2019. Follow-up was completed in July 2019, and data were analyzed from September 21, 2016, to July 31, 2019. Weekly Centers for Disease Control and Prevention (CDC)-reported, state-level ILI activity was ascertained to assess the weekly odds of the primary outcome. The study population included 3094 patients with high-risk CV disease from participating centers in the US. Participants were randomized to high-dose trivalent or standard-dose quadrivalent influenza vaccine and revaccinated for up to 3 seasons. The primary outcome was the time to composite of all-cause death or CP hospitalization within each season. Additional measures included weekly CDC-reported ILI activity data by state. Among 3094 participants (mean [SD] age, 65 [12] years; 2309 male [75%]), we analyzed 129 285 person-weeks of enrollment, including 1396 composite primary outcome events (1278 CP hospitalization, 118 deaths). A 1% ILI increase in the prior week was associated with an increased risk in the primary outcome (odds ratio [OR], 1.14; 95% CI, 1.07-1.21; P < .001), CP hospitalization (OR, 1.13; 95% CI, 1.06-1.21; P < .001), and CV hospitalization (OR, 1.12; 95% CI, 1.04-1.19; P = .001), after adjusting for state, demographic characteristics, enrollment strata, and CV risk factors. Increased ILI activity was not associated with all-cause death (OR, 1.00; 95% CI, 0.88-1.13; P > .99). High-dose compared with standard-dose vaccine did not significantly reduce the primary outcome, even when the analysis was restricted to weeks of high ILI activity (OR, 0.88; 95% CI, 0.65-1.20; P = .43). Traditionally warmer months in the US were associated with lower CV risk independent of local ILI activity. In this secondary analysis of a randomized clinical trial, ILI activity was temporally associated with increased CP events in patients with high-risk CV disease, and a higher influenza vaccine dose did not significantly reduce temporal CV risk. Other seasonal factors may play a role in the coincident high rates of ILI and CV events. ClinicalTrials.gov Identifier: NCT02787044.

Fractional Flow Reserve–Negative High-Risk Plaques and Clinical Outcomes After Myocardial Infarction

Even after fractional flow reserve (FFR)-guided complete revascularization, patients with myocardial infarction (MI) have high rates of recurrent major adverse cardiovascular events (MACE). These recurrences may be caused by FFR-negative high-risk nonculprit lesions. To assess the association between optical coherence tomography (OCT)-identified high-risk plaques of FFR-negative nonculprit lesions and occurrence of MACE in patients with MI. PECTUS-obs (Identification of Risk Factors for Acute Coronary Events by OCT After STEMI [ST-segment elevation MI] and NSTEMI [non-STEMI] in Patients With Residual Non-flow Limiting Lesions) is an international, multicenter, prospective, observational cohort study. In patients presenting with MI, OCT was performed on all FFR-negative (FFR > 0.80) nonculprit lesions. A high-risk plaque was defined containing at least 2 of the following prespecified criteria: (1) a lipid arc at least 90°, (2) a fibrous cap thickness less than 65 μm, and (3) either plaque rupture or thrombus presence. Patients were enrolled from December 14, 2018, to September 15, 2020. Data were analyzed from December 2, 2022, to June 28, 2023. The primary end point of MACE, a composite of all-cause mortality, nonfatal MI, or unplanned revascularization, at 2-year follow-up was compared in patients with and without a high-risk plaque. A total of 438 patients were enrolled, and OCT findings were analyzable in 420. Among included patients, mean (SD) age was 63 (10) years, 340 (81.0) were men, and STEMI and non-STEMI were equally represented (217 [51.7%] and 203 [48.3%]). A mean (SD) of 1.17 (0.42) nonculprit lesions per patient was imaged. Analysis of OCT images revealed at least 1 high-risk plaque in 143 patients (34.0%). The primary end point occurred in 22 patients (15.4%) with a high-risk plaque and 23 of 277 patients (8.3%) without a high-risk plaque (hazard ratio, 1.93 [95% CI, 1.08-3.47]; P = .02), primarily driven by more unplanned revascularizations in patients with a high-risk plaque (14 of 143 [9.8%] vs 12 of 277 [4.3%]; P = .02). Among patients with MI and FFR-negative nonculprit lesions, the presence of a high-risk plaque is associated with a worse clinical outcome, which is mainly driven by a higher number of unplanned revascularizations. In a population with a high recurrent event rate despite physiology-guided complete revascularization, these results call for research on additional pharmacological or focal treatment strategies in patients harboring high-risk plaques.

Toxicity spectrum and risk factors for chemo-immunotherapy in locally advanced or metastatic lung cancer.

Chemo-immunotherapy has become the best first-line treatment for advanced lung cancer patients without oncogenic drivers. However, it may also lead to an increased incidence and severity of treatment-related adverse events. In this retrospective study, lung cancer patients administrated with either anti-PD-1 or anti-PD-L1 treatment plus chemotherapy were included. Data on demographic characteristics, disease characteristics, treatment strategies, laboratory results, and clinical outcomes were collected from the Electronic Medical Records System and evaluation scales. Chi-square, univariate, and multivariate logistic regression analyses were used to identify the risk factors for immune-related adverse events (irAEs). A total of 116 patients were included in the study, and the majority experienced treatment-related adverse events. Adverse events of any grade were reported in 114 (98.3%) patients, with 73 (62.9%) experiencing Grade 3 or higher events. The most frequent adverse events were anemia (67.2%), decreased appetite (62.9%), and alopecia (53.4%). Fifty-four (46.6%) patients were diagnosed with irAEs, with hypothyroidism (28.4%) being the most commonly reported. Multivariable analysis demonstrated a significant correlation between the number of treatment cycles, elevated baseline levels of thyroid stimulating hormone (TSH) and interleukin-6 (IL-6) with irAEs (OR = 1.222, P = 0.009, OR = 1.945, P = 0.016, OR = 1.176, P = 0.004), and IL-6 was identified as a strong predictor of severe irAEs (OR = 1.084, P = 0.014). Our study demonstrated the safety of chemo-immunotherapy in lung cancer patients without additional toxicity. The number of treatment cycles, higher baseline levels of TSH and IL-6 were identified as potential clinical biomarkers for irAEs.

Left atrial function index predicts poor outcomes in acute myocardial infarction patients treated with percutaneous coronary intervention.

The left atrial function index (LAFI) is an index that combines the left atrial emptying fraction, adjusted left atrial volume and stroke volume. The prognostic value of LAFI in acute myocardial infarction (AMI) patients treated with percutaneous coronary intervention (PCI) is unknown. This study aims to determine whether LAFI predicts prognosis in AMI patients treated with PCI. Patients with newly diagnosed AMI who were treated with PCI at Hunan Provincial People's Hospital from March 2020 to October 2021 were prospectively enrolled. All patients underwent transthoracic echocardiography (TTE) at baseline and follow-up. The endpoint events included rehospitalization due to unstable angina, nonfatal myocardial infarction, rehospitalization due to heart failure and cardiovascular death. A total of 368 patients with AMI (92 women; mean age, 61.45 ± 11.91 years) were studied with a median follow-up of 14 ± 6.58 months. Sixty-nine patients had endpoint events. Patients who presented with events had a significantly lower LAFI than patients without events (34.25 ± 12.86 vs. 48.38 ± 19.42, P < 0.0001). Multivariate Cox analysis demonstrated that LAFI (HR = 0.97 [95% CI: 0.95; 0.99]; P = 0.012) and the Killip classification (HR = 1.51 [95% CI: 1.03; 2.22]; P = 0.034) were independently predictive of endpoint events. Kaplan-Meier survival curves showed that patients with LAFI ≤ 40.17 cm/ml/m2 had higher events than patients with LAFI > 40.17 cm/ml/m2 (HR = 8.53 [95% CI: 4.74; 15.35]; P < 0.0001). LAFI is a strong and independent predictor of adverse events and can be used for risk stratification in patients with AMI treated with PCI.

Abstract 085: Monocytes-derived Cytokines Induce Endothelial Dysfunction In Primary Aldosteronism

Due to aldosterone excess and its pleotropic effects, patients with primary aldosteronism (PA) are exposed to high rates of cardiovascular events. Endothelial dysfunction is the first step in the development of vascular disease and monocytes are an important immune cell type inducing vascular damage. Therefore, we measured endothelial function between PA patients and healthy controls and analyzed the impact of monocytes-derived cyctokines on the development of endothelial dysfunction. Endothelial function was measured in 13 healthy controls, 42 PA patients before and in 22 patients 6 months after initiation of a specific treatment using flow mediated dilation method (FMD). Monocytes were isolated from 6 healthy individuals as well as from 8 PA patients before and treatment. Cytokine profile was measured by a Human Cytokine 17-plex Assay (Bio-rad). The effects of monocyte-derived cytokines on endothelial function were studied by wire myography in pre-constricted thoracic aortic pieces of healthy mice. FMD was significantly lower among PA patients compared to controls. Surgical or pharmacological treatment significantly improved endothelial function in PA patients. Monocytes from untreated patients with PA secreted significantly higher concentrations of the following cytokines and growth factors than healthy controls: G-CSF, IFN-γ, TNF-α, IL-6, IL-10, IL-8, IL-17, and MCP-1. Especially concentrations of IL-6 (388 (351-580)pg/ml vs. 36(4-268)pg/ml, p&lt;0.05) and TNF-α (95(48-135)pg/ml vs 17(5-41)pg/ml, p&lt;0.05) were much higher among PA patients. In pre-constricted murine aortas, 24 hours incubation of the secretome from untreated patients with PA induced an impaired endothelial vasodilation compared to the secretome of the controls. Interestingly, in comparison to untreated patients, treatment of PA not only reduced monocytes-derived cytokine levels, but also improved endothelial dysfunction in pre-constricted aortas incubated with the corresponding secretome. Endothelial function is impaired in PA. This impairment seem to be in part mediated by an increased release of pro-inflammatory cytokines from monocytes. PA treatment reduced the pro-inflammatory activity of monocytes and improved endothelial function.

Underutilization of Mineralocorticoid Antagonists in Patients With Heart Failure With Reduced Ejection Fraction

BackgroundIt is unknown how the efficacy and safety of mineralocorticoid receptor antagonists vary according to duration of heart failure with reduced ejection fraction (HFrEF). ObjectivesIn this study, we sought to evaluate the safety and efficacy of eplerenone according to duration of HFrEF. MethodsIn the EMPHASIS-HF trial, 3 patient groups were created according to HFrEF duration: <1 year, 1 to <5 years, and ≥5 years. The primary outcome was the composite of heart failure (HF) hospitalization or cardiovascular death. Outcomes were adjusted for prespecified prognostic variables and examined with the use of Cox regression models. ResultsThe numbers of patients in each group were: 975, <1 year; 769, 1 to <5 years; and 988, ≥5 years. Patients with longer-standing HF were older and more frequently had cardiovascular and noncardiovascular comorbidities. The rate of the primary outcome (per 100 person-years) increased with HFrEF duration: 9.8 (95% CI: 8.4-11.4) for <1 year, 13.5 (95% CI: 11.6-15.7) for 1 to <5 years, and 17.6 (95% CI: 15.6-19.8) for ≥5 years. The benefits of eplerenone were consistent across HF duration: HRs for the primary outcome were 0.57 (95% CI: 0.42-0.79) for <1 year, 0.81 (95% CI: 0.60-1.10) for 1 to <5 years, and 0.61 (95% CI: 0.48-0.78) for ≥5 years; Pinteraction = 0.24. The absolute benefit was greatest in the longest-duration group: the number needed to treat for the primary outcome was 14 for <1 year, 13 for 1 to <5 years, and 10 for ≥5 years duration. ConclusionsPatients with longer-standing HFrEF had worse clinical status and a higher rate of events, but the benefit of eplerenone was consistent regardless of HFrEF duration. (A Comparison of Outcomes in Patients in NYHA Class II Heart Failure When Treated With Eplerenone or Placebo in Addition to Standard Heart Failure Medicines [EMPHASIS-HF]; NCT00232180)

ThTP6.5 Long term major adverse cardiovascular events following myocardial injury after non-cardiac surgery (MINS): A systematic review and meta-analysis

Abstract Aims Myocardial injury after non-cardiac surgery (MINS) is diagnosed following asymptomatic troponin elevation in the perioperative period. MINS is associated with high mortality rates and significant rates of major adverse cardiac events (MACE) within the first 30 days following surgery. However, less is known regarding its impact on mortality and morbidity beyond this time. This systematic review and meta-analysis aims to establish the rates of long term morbidity and mortality associated with MINS. Methods This review was registered with PROSPERO (CRD42021283995). Medline, EMBASE and Cochrane CENTRAL were searched, and abstracts screened by two reviewers. Observational studies and control arms of trials reporting mortality and cardiovascular outcomes beyond 30 days in adult patients diagnosed with MINS following non-cardiac surgery were included. Risk of bias was assessed using the Quality in Prognostic Studies tool (QUIPS). A random effects model was used for meta-analysis of outcome subgroups. Results Searches identified 40 studies. Meta-analysis of 37 cohort studies found a rate of MACE associated MINS of 21% and mortality following MINS was 25% at one year follow-up. A non-linear increase in mortality rates was observed up to 1 year post surgery. MACE rates were also lower in elective surgery compared to a subgroup which included emergency cases. Analysis demonstrated a wide variety of accepted MINS and MACE diagnostic criteria within the included studies. Conclusions A diagnosis of MINS is associated with high rates of poor cardiovascular outcomes up to one year. Work is needed to standardise diagnostic criteria and reporting of MINS related outcomes.

Flavor-dependent long-range neutrino interactions in DUNE & T2HK: alone they constrain, together they discover

Discovering new neutrino interactions would represent evidence of physics beyond the Standard Model. We focus on new flavor-dependent long-range neutrino interactions mediated by ultra-light mediators, with masses below 10−10 eV, introduced by new lepton-number gauge symmetries Le – Lμ, Le – Lτ, and Lμ – Lτ. Because the interaction range is ultra-long, nearby and distant matter — primarily electrons and neutrons — in the Earth, Moon, Sun, Milky Way, and the local Universe, may source a large matter potential that modifies neutrino oscillation probabilities. The upcoming Deep Underground Neutrino Experiment (DUNE) and the Tokai-to-Hyper-Kamiokande (T2HK) long-baseline neutrino experiments will provide an opportunity to search for these interactions, thanks to their high event rates and well-characterized neutrino beams. We forecast their probing power. Our results reveal novel perspectives. Alone, DUNE and T2HK may strongly constrain long-range interactions, setting new limits on their coupling strength for mediators lighter than 10−18 eV. However, if the new interactions are subdominant, then both DUNE and T2HK, together, will be needed to discover them, since their combination lifts parameter degeneracies that weaken their individual sensitivity. DUNE and T2HK, especially when combined, provide a valuable opportunity to explore physics beyond the Standard Model.

'Spikeopathy': COVID-19 Spike Protein Is Pathogenic, from Both Virus and Vaccine mRNA.

The COVID-19 pandemic caused much illness, many deaths, and profound disruption to society. The production of 'safe and effective' vaccines was a key public health target. Sadly, unprecedented high rates of adverse events have overshadowed the benefits. This two-part narrative review presents evidence for the widespread harms of novel product COVID-19 mRNA and adenovectorDNA vaccines and is novel in attempting to provide a thorough overview of harms arising from the new technology in vaccines that relied on human cells producing a foreign antigen that has evidence of pathogenicity. This first paper explores peer-reviewed data counter to the 'safe and effective' narrative attached to these new technologies. Spike protein pathogenicity, termed 'spikeopathy', whether from the SARS-CoV-2 virus or produced by vaccine gene codes, akin to a 'synthetic virus', is increasingly understood in terms of molecular biology and pathophysiology. Pharmacokinetic transfection through body tissues distant from the injection site by lipid-nanoparticles or viral-vector carriers means that 'spikeopathy' can affect many organs. The inflammatory properties of the nanoparticles used to ferry mRNA; N1-methylpseudouridine employed to prolong synthetic mRNA function; the widespread biodistribution of the mRNA and DNA codes and translated spike proteins, and autoimmunity via human production of foreign proteins, contribute to harmful effects. This paper reviews autoimmune, cardiovascular, neurological, potential oncological effects, and autopsy evidence for spikeopathy. With many gene-based therapeutic technologies planned, a re-evaluation is necessary and timely.

Admission LDL-cholesterol, statin pretreatment and early outcomes in acute ischemic stroke

Lipid paradox of low LDL-C may cause physicians to be reluctant to use statins in acute ischemic stroke (AIS) patients with low LDL-C levels at admission. This study investigated the association between LDL-C levels and early vascular outcomes and assessed the potential interaction effect between LDL-C and statin pretreatment on early outcomes. This was a study of a prospective, multicenter, registry of AIS patients with admission LDL-C. The subjects were divided into 3 groups according to LDL-C levels: low LDL-C (≤100mg/dL); intermediate LDL-C (>100, <130 mg/dL); and high LDL-C (≥130mg/dL). The primary early vascular outcome was a composite of stroke (ischemic or hemorrhagic), myocardial infarction and all-cause mortality within 3 months. The associations of LDL-C levels as a continuous variable and the risks of primary outcome using Cox proportional hazards models with restricted cubic splines were explored. A total of 32,505 patients (age, 69±12; male, 58.6%) were analyzed. The 3 groups showed significant differences in the 3-month primary outcome, with highest events in the low LDL-C group; after adjustment, no significant associations with the 3-month primary outcome remained. U-shaped nonlinear relationships of LDL-C levels with the 3-month primary outcome were observed (Pnon-linearity<0.001), with substantial relationships in the no pretreatment subgroup. The relationships between admission LDL-C levels and early outcomes are complex but appear to be paradoxical in patients with low LDL-C and no statin pretreatment. The results suggest that statin pretreatment might offset the paradoxical response of low LDL-C on early vascular outcomes. Further study would be warranted.

Clinical outcomes after successful revascularization of long chronic total occlusions using amphilimus-eluting polymer-free stent: a single center experience.

Chronic total occlusions (CTOs) are complex lesions that usually require stenting of long segments, and, therefore more prone to restenosis and/or thrombosis. Polymer-free stents to avoid chronic inflammatory response in the vessel wall are a potential solution to reduce target lesion revascularization. We, therefore, investigated the clinical outcomes following successful amphilimus-eluting polymer-free stent implantation in long CTOs. A total of 77 consecutive patients who underwent successful revascularization for long CTOs (lesion length ≥30 mm) using Cre8 stents were included. Baseline demographics, periprocedural characteristics, in-hospital events, and post-discharge long-term cardiovascular events were retrospectively screened for all patients. The Japanese CTO score was 1.58 ± 0.96, and the lesion length was 54.0 ± 9.89 mm. All cases were technically successful (n = 77, 100%), while procedural success was obtained in 74 patients (96.1%). Periprocedural complications were contrast-induced nephropathy (n = 4, 5.2%), coronary perforation (n = 3, 3.8%), residual dissection (n = 1, 1.3%), and femoral artery pseudoaneurysm (n = 1, 1.3%). Three patients (3.9%) presented periprocedural myocardial infarction requiring repeat percutaneous coronary intervention. At 25.0 ± 15.8 months follow-up, major adverse cardiac and cerebrovascular events were observed in 14 patients (18.1%). The Cre8 polymer-free drug- eluting stents seems safe and effective for percutaneous revascularization of long CTO lesions with a high success and low adverse event rate.

Racial differences in longitudinal toxicities of anticancer agents in early phase cancer clinical trials.

Racial differences have been reported in toxicity outcomes for anticancer drug treatments. However, these observations were often from studies with small sample sizes, and many only reported the maximum grade of toxicity and no longitudinal information. This current analysis aims to investigate racial differences in longitudinal toxicities using a large-scale clinical trials database. Early-phase clinical trials sponsored by the Cancer Therapy Evaluation Program at the National Cancer Institute, USA, that evaluated cytotoxic drugs and molecularly targeted agents between March 2000 and December 2012 were studied. Race was categorized as White, Black or African-American, and Asian. Each toxicity's grade prevalence, mean grade at each cycle, and time to develop grade 2 or higher toxicity was evaluated. In total, 25,442 patients from 697 trials were included in this study. The number of patients categorized as White, Black, and Asian designations was 22,756 (89%), 1874 (7%), and 812 (3%), respectively. Notable findings include the rate of any grade of diarrhea in Black people was 26% and 21% lower than that of White and Asian people. The median time to the first grade 2 or higher event was 6 cycles in White people, 8 in Black people, and 6 in Asian people. The rate of any grade hyperglycemia was significantly higher in Asian people. Although we identified several racial differences in longitudinal toxicities, most were of generally lower grade. Further study is needed to clarify the cause of racial differences in treatment-associated toxicities.

Subjective and Objective Measurements of the Facial Effects of Microdoses of Botulinum Toxin.

Studies have suggested that botulinum toxin A may improve skin quality, and application protocols using hyper-diluted doses of botulinum toxin (microdosing) have been studied as a way to achieve therapeutic goals without fully paralyzing the targeted muscles. To evaluate the effects of a combined protocol utilizing both the standard dosing and the microdosing of AbobotulinumtoxinA for the improvement of skin quality, measured by objective and subjective measurements. Thirty patients were treated with botulinum toxin using both the standard technique and the microdosing technique. Objective (Sebumeter®, Mexameter® and digital dermoscopy pictures) and subjective (Global Aesthetic Improvement Scale and a clinical scale for evaluating the quality of facial skin) measurements of the effects in the treated areas were taken to assess the efficacy of the treatment. Digital dermoscopy showed a marked reduction of erythema and telangiectasias. Erythema and telangiectasias improved both on objective and subjective measurements. Skin oleosity, static rhytids, papules and pustules and enlarged pores improved on subjective measurements. Patient satisfaction was high (93%) despite the high rate of adverse events (56%). The combined application of standard doses and microdoses of AbobotulinumtoxinA is effective in improving the overall quality of facial skin. The effects on erythema and telangiectasias suggest that it is an effective treatment option for patients with erythematotelangiectatic rosacea. When applying microdoses of botulinum toxin in the lower and mid-face, the doses and pattern of injection should be customized for each patient to reduce the occurrence of adverse events.

Aggregate Clinical and Biomarker-Based Model Predicts Adverse Outcomes in Patients With Coronary Artery Disease

Despite guideline-based therapy, patients with coronary artery disease (CAD) are at widely variable risk for cardiovascular events. This variability demands a more individualized risk assessment. Herein, we evaluate the prognostic value of 6 biomarkers: high-sensitivity C-reactive protein, heat shock protein-70, fibrin degradation products, soluble urokinase plasminogen activator receptor, high-sensitivity troponin I, and B-type natriuretic peptide. We then develop a multi-biomarker-based cardiovascular event prediction model for patients with stable CAD. In total, 3,115 subjects with stable CAD who underwent cardiac catheterization at Emory (mean age 62.8years, 17% Black, 35% female, 57% obstructive CAD, 31% diabetes mellitus) were randomized into a training cohort to identify biomarker cutoff values and a validation cohort for prediction assessment. Main outcomes included (1) all-cause death and (2) a composite of cardiovascular death and nonfatal myocardial infarction (MI) within 5years. Elevation of each biomarker level was associated with higher event rates in the training cohort. A biomarker risk score was created using optimal cutoffs, ranging from 0 to 6 for each biomarker exceeding its cutoff. In the validation cohort, each unit increase in the biomarker risk score was independently associated with all-cause death (hazard ratio 1.62, 95% confidence interval [CI] 1.45 to 1.80) and cardiovascular death/MI (hazard ratio 1.52, 95% CI 1.35 to 1.71). A biomarker risk prediction model for cardiovascular death/MI improved the c-statistic (∆ 6.4%, 95% CI 3.9 to 8.8) and net reclassification index by 31.1% (95% CI 24 to 37), compared with clinical risk factors alone. Integrating multiple biomarkers with clinical variables refines cardiovascular risk assessment in patients with CAD.

Development of simultaneous multi-channel data acquisition system for large-area Compton camera (LACC)

The large-area Compton camera (LACC), featuring significantly high detection sensitivity, was developed for high-speed localization of gamma-ray sources. Due to the high gamma-ray interaction event rate induced by the high sensitivity, however, the multiplexer-based data acquisition system (DAQ) rapidly saturated, leading to deteriorated energy and imaging resolution at event rates higher than 4.7 × 103 s−1. In the present study, a new simultaneous multi-channel DAQ was developed to improve the energy and imaging resolution of the LACC even under high event rate conditions (104–106 s−1). The performance of the DAQ was evaluated with several point sources under different event rate conditions. The results indicated that the new DAQ offers significantly better performance than the existing DAQ over the entire energy and event rate ranges. Especially, the new DAQ showed high energy resolution under very high event rate conditions, i.e., 6.9% and 8.6% (for 662 keV) at 1.3 × 105 and 1.2 × 106 s−1, respectively. Furthermore, the new DAQ successfully acquired Compton images under those event rates, i.e., imaging resolutions of 13.8° and 19.3° at 8.7 × 104 and 106 s−1, which correspond to 1.8 and 73 μSv/hr or about 18 and 730 times the background level, respectively.

CL-Impute: A contrastive learning-based imputation for dropout single-cell RNA-seq data

Background:Single-cell RNA-sequencing (scRNA-seq) technology has revolutionized the study of cell heterogeneity and biological interpretation at the single-cell level. However, the dropout events commonly present in scRNA-seq data can markedly reduce the reliability of downstream analysis. Existing imputation methods often overlook the discrepancy between the established cell relationship from dropout noisy data and reality, which limits their performances due to the learned untrustworthy cell representations. Method:Here, we propose a novel approach called the CL-Impute (Contrastive Learning-based Impute) model for estimating missing genes without relying on preconstructed cell relationships. CL-Impute utilizes contrastive learning and a self-attention network to address this challenge. Specifically, the proposed CL-Impute model leverages contrastive learning to learn cell representations from the self-perspective of dropout events, whereas the self-attention network captures cell relationships from the global-perspective. Results:Experimental results on four benchmark datasets, including quantitative assessment, cell clustering, gene identification, and trajectory inference, demonstrate the superior performance of CL-Impute compared with that of existing state-of-the-art imputation methods. Furthermore, our experiment reveals that combining contrastive learning and masking cell augmentation enables the model to learn actual latent features from noisy data with a high rate of dropout events, enhancing the reliability of imputed values. Conclusions:CL-Impute is a novel contrastive learning-based method to impute scRNA-seq data in the context of high dropout rate. The source code of CL-Impute is available at https://github.com/yuchen21-web/Imputation-for-scRNA-seq.

What are the Best Drugs and Combinations in Afro-Descendant Hypertensive Patients?

Hypertension in African descendants occurs early, with high rates of cardiovascular events compared to Caucasians. In addition, genetic influence, low levels of plasma renin activity, greater sensitivity to salt, low sodium secretion, and other mechanisms are involved and discussed in this article. For pharmacological treatment, several studies were evaluated, such as CREOLE, ALLHAT, CARDIA, JHS, REGARDS, AASK, ACCOMPLISH, review articles and meta-analyzes and some guidelines, such as European, American, Brazilian to compare treatment indication. Several pharmacological classes, such as calcium channel blockers, Β-blockers, renin angiotensin system inhibitors, aldosterone and diuretics were included in present review in order to compare utilization and indication for Afro-descendant hypertensive patients. We concluded that several relevant points should be considered in the pharmacological treatment of African descendants that include pathophysiological characteristics, early development of lesions in target organs, in addition to higher rates of cardiovascular and renal events. In addition to lifestyle changes, improved nutrition, combined treatment, probably as a first-line treatment, should be considered as an approach, and the drugs used should aim at blood pressure control and inhibition of the inflammatory process, which results in worse outcomes. It is important to highlight that the representativeness of the Afro-descendant population was unsatisfactory for a robust conclusion. in this population, we can infer from the initial pharmacological treatment the use of thiazide-like diuretics, or dihydropyridine calcium channel blocker should be considered, although the institution of fixed combinations with angiotensin enzyme conversion inhibitors or angiotensin receptor blockers are important in the protection of target organs that occurs earlier and more seriously.

Outcomes of symptomatic penetrating aortic ulcer and intramural hematoma in the endovascular era

BackgroundAlthough endovascular technology has resulted in a paradigm shift in treatment, medical management remains the standard of care for penetrating aortic ulcer (PAU) and intramural hematoma (IMH). This study aimed to detail the short- and long-term outcomes of symptomatic PAU/IMH. MethodsInstitutional data on symptomatic PAU/IMH were gathered (2005-2020). The primary outcome was the composite of recurrent symptoms, radiographic progression, intervention, rupture, and death from related or unknown cause. Factors associated with the primary outcome were determined using a Fine-Gray model with death from an unrelated cause as a competing risk. ResultsA total of 83 symptomatic patients treated with medical management aside from ruptures and type A dissections: 21 isolated PAU, 30 isolated IMH, and 32 IMH and PAU. Adverse outcomes included symptom recurrence in 14 (16.9%), radiographic progression to dissection or saccular aneurysm in 17 (20.5%), surgery in 20 (24.1%) (17 thoracic endovascular aortic repair, 1 endovascular aortic repair, 1 frozen elephant trunk, and 1 open repair), and rupture in 4 (4.8%). Twenty-seven patients (32.5%) died during follow-up: 6 from IMH treatment complications, 8 from an unknown cause, and 13 from other causes. The 30-day, 1-year, and 5-year cumulative incidences of the primary outcome was 26.5% (95% confidence interval [CI], 16.9%-37.0%), 44.9% (95% CI, 32.8%-56.2%), and 57.5% (95% CI, 42.4%-69.9%), respectively. IMH with PAU was associated with a significantly higher risk of the primary outcome compared with isolated IMH (subdistribution hazard ratio, 2.21; 95% CI, 1.09-4.50; P = .027) and isolated PAU (subdistribution hazard ratio, 3.58; 95% CI, 1.44-8.88; P = .006). ConclusionsComplications from symptomatic PAU and IMH are frequent, with intervention, recurrent symptoms, radiographic progression, rupture, or death affecting 25% of patients at 30 days after diagnosis and almost one-half of patients 1 year after diagnosis. Given the high rate of adverse events in this population, investigation into a more aggressive interventional strategy may warranted, especially in patients with a combined IMH and PAU.

The Role of Neutrophil to Lymphocyte Ratio and its Common Clinical Outcomes Among Patients with Non-ST Elevation Acute Coronary Syndrome.

To evaluate the admission neutrophil-to-lymphocyte ratio (NLR) for risk stratification for in-hospital outcomes and complications in non-ST-elevation acute coronary syndrome (non-ST-ACS) patients. We recruited consecutive patients with non-ST-ACS. The NLR was obtained and stratified as low, intermediate, and high-risk based on <3.0, 3.0-6.0, and >6.0, respectively. The new ST-T changes, arrhythmias, contrast-induced nephropathy (CIN), and mortality were recorded. Median NLR was 3 [2.1-5.3] for 346 patients with 19.9% and 30.6% in high- and intermediate-risk group. New ST-T changes were observed in 3.5% (12) out of which 8, 3, and 1 patient in low, intermediate, and high-risk group (p = 0.424), respectively. Arrhythmias were observed in 5.8% (20) with 7, 5, and 8 patients in low, intermediate, and high-risk group (p = 0.067), respectively. CIN was observed in 4.9% (17) with 5, 5, and 7 in low, intermediate, and high-risk group (p = 0.064), respectively. In-hospital mortality was recorded in 1.4% (5) with 2 and 3 patients in high and low-risk group (p = 0.260), respectively. A significant number of non-ST-ACS patients fall in the high-risk category of NLR. Although, the association between NLR and in-hospital mortality and adverse events was not statistically significant but relatively higher rates of events were observed in high risk group.

Eye Movement Desensitization and Reprocessing Therapy for Individuals With Neurodevelopmental Disorders: A Systematic Review

Children, young people, and adults with neurodevelopmental disorders (NDDs), including autism and attention-deficit hyperactivity disorder (ADHD), are known to be at risk of experiencing high rates of traumatic events. EMDR is an evidence-based psychological therapy for trauma and mental health conditions in the general population. A systematic search was conducted to find research studies using EMDR with individuals with certain NDDs across the lifespan. A total of 15 studies were included in this review, 13 of which were case studies/series. Although findings are inconclusive as to whether EMDR can be effective for individuals with NDDs, it is encouraging that all the studies included in the review reported a reduction in posttraumatic stress disorder symptoms. However, more robust research examining the effectiveness of EMDR for people with NDDs is needed.