bluuebunny/crossref_metadata_2025_split huggingface dataset:
Collaterals and extent of myocardial injury in patients with acute coronary syndromes – an analysis of the prospective SPUM-ACS cohort
Authors: Obeid S , Adjibodou B , Denegri A , Kraler S , Katsarov K , Roffi M , Raeber L , Muller O , Staehli B , Luescher T F 
Published: October 2022

Abstract

Introduction
The impact of collateral circulation in the presence of severe coronary artery disease such as chronic total occlusion (CTO) has been extensively studied, with results despite few discrepancies, supporting an overall benefit on preservation of myocardial tissue and left ventricular ejection fraction (LVEF). However, less is known about the protective effects of collaterals in the context of acute coronary syndromes (ACS). In the current study we sought to analyze the incidence, grade and impact of collateral circulation in a large prospectively recruited cohort of patients presenting with ACS with independent events adjudication.

Methods and results
4'546 ACS patients presenting with ACS, enrolled in the prospective Special Program University Medicine ACS (SPUM-ACS) cohort were included. The current analysis showed the presence of a collateralized culprit lesion in 12.9% (n=586) of patients, 84% (n=492) originating from the contralateral side and 16% (n=94) from the ipsilateral side. Of those 64.6% (n=378) were being graded as Rentrop 2 or more. There were no differences in baseline characteristics between the two groups including incidence of diabetes, coronary artery disease, age and gender. However, despite the presence of collaterals graded Rentrop 2 or more, those patients had a significantly lower LVEF mean 48,44% vs 51.6%, p=0.025 and higher creatinine Kinase levels, mean (CK) 981 U/I vs 957 UI, p&lt;0.001 as compared to patients with absent collateral-circulation on admission. Interestingly a sub analysis of the STEMI population showed no significant differences in both LVEF and CK at presentation, while troponin (TNT) plasma levels were significantly lower in patients with collaterals (mean TNT 0.0031 ug/l vs 0.035 ug/l p=0.001). Additionally no differences in cardiovascular mortality, stent thrombosis or MI was seen at one year follow-up.

Conclusion
The current analysis highlights a possible protective impact of a pre-existing collateral circulation against myocardial injury in the setting of ACS and ST elevation myocardial infarction. However this was not translated into improvement in hard outcomes acutely and up to one year of follow up, but may be important in the long run.

Funding Acknowledgement
Type of funding sources: Public Institution(s). Main funding source(s): Swiss National Research Foundation - ZurichHeart House
Age as a prognostic modifier in anemic patients discharged after acute coronary syndrome
Authors: Cazorla-Morallon D , Cordero A , Tomas-Simon F J , Sanchez-Munuera S , Alvarez-Alvarez B , Cid-Alvarez B , Garcia-Acuna J M , Rodriguez-Manero M , Escribano D , Bertomeu-Gonzalez V , Zuazola P , Gonzalez-Juanatey J R 
Published: October 2022

Abstract

Introduction
The presence of anemia on admission is a poor long-term prognostic factor in patients diagnosed with acute coronary syndrome (ACS). However, it is unknown whether age is a factor modifying the effect of anemia on mortality.

Objective
To determine the effect of age on anemia in terms of long-term mortality in patients admitted for ACS.

Methods
This is an observational study in which we included all patients discharged from cardiology for ACS in two centers from 2003 to 2020. Patients with anemia were classified by hemoglobin values &lt;13 g/dL in men and &lt;12 g/dL in women in the first blood count performed during hospitalization. The interaction between age and anemia was analyzed using the Cox regression model and the chunk test. We analyzed the effect of anemia on mortality using the Cox regression model adjusted for several confounding variables and the interaction with age.

Results
We included 8872 patients diagnosed with ACS, with a mean age of 66.38 (SD ±12.76) years, 27.1% female and 34.3% diagnosed with ST-segment elevation ACS. The mean hemoglobin value was 13.88 (SD ±1.85) g/dL and 20.5% of patients were anemic on admission.
During follow-up (median 1764 days, IQR 694–2439 days) there was an increased risk of all-cause mortality in patients with anemia adjusted for age and other risk factors (sex, renal function, GRACE score, atrial fibrillation, LVEF and previous revascularization), HR 15.5 (CI 5.77–41.75; p&gt;0.005). We found a significant interaction between age and anemia (p&lt;0.01). As represented in the figure, the adjusted risk of mortality decreased at older ages; in patients whose age was &gt;80 anemia was not associated to higher mortality risk. Similar results were observed for cardiovascular mortality, HR 21.36 (CI 6.13–74.43, p&gt;0.005).

Conclusion
Age modifies the risk of mortality in patients discharged after an ACS being the risk of mortality higher in youngest ages and disappearing in octogenearians. There results should be taken under consideration for the treatment and management of ACS patients.

Funding Acknowledgement
Type of funding sources: None.
Trends in mortality and ischemic outcomes in patients with ST-segment elevation myocardial infarction following implementation of a primary percutaneous coronary intervention strategy, 2003–2017
Authors: Thrane P , Olesen K K W , Thim T , Gyldenkerne C , Kristensen S D , Maeng M 
Published: October 2022

Abstract

Introduction
In Denmark, primary percutaneous coronary intervention (pPCI) has served as the national reperfusion strategy in ST-segment elevation myocardial infarction (STEMI) since 2003. Since then, extensive changes in management and treatment of patients with STEMI have been introduced. We investigated the temporal trends in one-year mortality and ischemic outcomes after STEMI.

Methods
We included all first-time STEMI patients treated with pPCI in Western Denmark from 2003 to 2017. Patients were categorized into four time periods based on year of pPCI treatment (2003–2006, 2007–2010, 2011–2014, 2015–2017) and followed for one year. Outcomes included all-cause death, recurrent myocardial infarction (MI: follow-up started after 30 days post-pPCI since the validity of recurrent MI is low in the first 30 days), and ischemic stroke. We also identified a sex and age matched comparison cohort without prior cardiovascular disease from the Western Denmark general population. Groups were compared using sex- and age-adjusted hazard ratios (aHRs) by Cox regression with the first period as reference.

Results
A total of 18,538 STEMI patients and 92,690 individuals from the general population were included. One-year mortality in STEMI patients decreased from 10.8% in 2003–2006 to 7.8% in 2015–2017 (aHR 0.70, 95% CI 0.60–0.80), while it was steady in the general population cohort (figure). The one-year risk of recurrent MI and ischemic stroke also decreased from 2003–2006 to 2015–2017 (MI: 3.5% vs. 2.4%, aHR: 0.66, 95% CI 0.51–0.86; ischemic stroke: 2.5% vs. 1.9%, aHR 0.58, 95% CI 0.42–0.80). These improvements coincided with increased up-take of evidence-based treatments, especially drug-eluting stents (39% vs. 90%), high-intensity statins (3% vs. 87%), and newer antiplatelet agents.

Conclusions
From 2003 to 2017, the one-year risk of death, recurrent MI, and ischemic stroke decreased substantially among patients with STEMI. These improvements occurred simultaneously with the gradual implementation of evidence-based guideline-directed treatments.

Funding Acknowledgement
Type of funding sources: Foundation. Main funding source(s): Aase and Ejnar Danielsen foundation
Right ventricular versus left ventricular global longitudinal strain for association with all-cause mortality after transcatheter aortic valve implantation
Authors: Winkler N , Anwer S , Tanner F C 
Published: October 2022

Abstract

Introduction
Speckle-tracking echocardiography plays an increasingly important role in the assessment of aortic stenosis (AS), the most common valvular heart disease in the Western population. Right ventricular (RV) and left ventricular (LV) global longitudinal strain (GLS) were studied for their association with all-cause mortality in AS patients undergoing transcatheter aortic valve implantation (TAVI).

Purpose
To investigate whether simultaneous assessment of RV and LV GLS provides a better association with all-cause mortality during long-term follow-up after TAVI.

Methods
In our prospective registry we identified 109 patients with severe AS who underwent TAVI and had a pre-procedural echocardiography within three months of the procedure allowing complete assessment of RV and LV GLS using TomTec Image Arena. All-cause mortality was defined as endpoint.

Results
RV GLS was lower among non-survivors (N=36; median [IQR]: −13.94 [−16.31 to −12.62]; p&lt;0.001) than survivors (N=73; −17.04 [−20.16 to −15.22]; p&lt;0.001), while LV GLS did not differ (p=0.249). RV GLS &gt;−16.6% differentiated survivors from non-survivors (sensitivity 78%; specificity 63%; ROC AUC 71%; p&lt;0.001), while LV GLS did not (p=0.243). Kaplan Meier curves showed good differentiation of survivors and non-survivors with the RV GLS (p&lt;0.001; Figure 1), but not the LV GLS cut-off (p=0.058). In univariable Cox regression models, RV GLS was associated with all-cause mortality (HR 1.10 [95% CI 1.02 to 1.18]; χ2=6.64; p=0.01), while LV GLS was not (HR 1.05 [0.96 to 1.16]; χ2=1.08; p=0.299). In bivariable models, association of RV GLS with all-cause mortality was independent of LV GLS or LV ejection fraction (LVEF; Table 1). ANOVA likelihood ratios revealed that inclusion of RV GLS to LV GLS or LVEF improved their model fitness, while that of LV GLS did not (Table).

Conclusion
RV GLS was associated with all-cause mortality after TAVI, while LV GLS and LVEF were not. The association of RV GLS was independent of LV GLS and LVEF and showed potential incremental value for assessment of outcome association, while LV GLS did not.

Funding Acknowledgement
Type of funding sources: None.
Peak atrial longitudinal strain as an independent predictor of composite endpoint in patients received aortic valve replacement for severe aortic stenosis: a prospective cohort study
Authors: Tsui L , Tse Y K , Yu S Y , Li H L , Ren Q W , Wu M Z , Yu S Y , Tse H F , Yiu K H 
Published: October 2022

Abstract

Objective
Severe aortic stenosis (AS) is the primary valvular heart disease, treatable only by aortic valve replacement (AVR). The prognostic value of pre-operative left atrial (LA) function on post-AVR clinical outcomes is uncertain. The study aims to evaluate the prognostic value of pre-operative peak atrial longitudinal strain (PALS) as a surrogate of LA function on post AVR all-cause mortality and heart failure hospitalisation.

Methods
Patients aged 18 years old or above with severe AS were recruited and assessed using speckle-tracking echocardiography pre-operatively. Severe AS was defined according to 2014 AHA/ACC Guideline for the Management of Patients with Valvular Heart Disease. PALS was measured. Based on the median value of PALS, patients were stratified into PALS &lt;15.94% and PALS &gt;15.94%. Patients with underlying pre-operative atrial fibrillation, other moderate to severe valvular heart diseases and cancers were excluded. Patients were followed up until death, heart failure hospitalisation or end of the study. The primary outcome is a composite endpoint of all-cause mortality and heart failure hospitalisation. The association of PALS with the composite endpoint was evaluated by Cox Proportional Hazards analysis.

Results
A total of 128 patients (mean age 65.32±9.42 years, 56.3% male) were prospectively analyzed. Patients were followed up for a mean period of 3.9±2.4 years. A total of 65 of 128 patients (50.8%) belonged to PALS&lt;15.94%. During the study period, 23 patients developed the adverse events. A lower pre-operative PALS, both as a continuous or a categorical variable, were associated with a higher unadjusted risk of adverse events (Continuous; HR, 0.93; 95% CI 0.88–0.98; p=0.011; PALS &lt;15.94%; HR, 4.94; 95% CI, 1.67–14.58; p=0.004).

Conclusion
The study demonstrated a lower pre-operative PALS is associated with all-cause mortality and heart failure admission in patients with severe AS undergoing AVR. Evaluation of LA function by assessing speckle tracking derived PALS may aid in prognostication for patients undergoing AVR.

Funding Acknowledgement
Type of funding sources: None.
Top and bottom longevity of nations: a retrospective analysis of the age-at-death distribution across 18 OECD countries
Authors: Verguet Stéphane , Niwa Miyu , Bolongaita Sarah 
Published: October 2022

Abstract

Background
Similar to the study of the distribution of income within countries, population-level health disparities can be examined by analyzing the distribution of age at death.

Methods
We sourced period-specific death counts for 18 OECD countries over 1900–2020 from the Human Mortality Database. We studied the evolution of country-year-specific distributions of age at death, with an examination of the lower and upper tails of these distributions. For each country-year, we extracted the 1st, 5th, 10th, 90th, 95th and 99th percentiles of the age-at-death distribution. We then computed the corresponding shares of longevity—the sum of the ages weighted by the age-at-death distribution as a fraction of the sum of the ages weighted by the distribution—for each percentile. For example, for the 10th percentile, this would correspond to how much longevity accrues to the bottom 10% of the age-at-death distribution in a given country-year.

Results
We expose a characterization of the age-at-death distribution across populations with a focus on the lower and upper tails of the distribution. Our metrics, specifically the gap measures in age and share across the 10th and 90th percentiles of the distribution, enable a systematic comparison of national performances, which yields information supplementary to the cross-country differences commonly pointed by traditional indicators of life expectancy and coefficient of variation.

Conclusions
Examining the tails of age-at-death distributions can help characterize the comparative situations of the better- and worse-off individuals across nations, similarly to depictions of income distributions in economics.
Investigation of the pharmacokinetic properties of synthetic heparan sulfate oligosaccharides
Authors: Arnold Katelyn , Wang Zhangjie , Lucas Andrew , Zamboni William , Xu Yongmei , Liu Jian 
Published: October 2022

AbstractHeparan sulfate (HS) is a sulfated polysaccharide with a wide range of biological activities. There is an increasing interest in the development of structurally homogeneous HS oligosaccharides as therapeutics. However, the factors influencing the pharmacokinetic properties of HS-based therapeutics remain unknown. Here, we report the pharmacokinetic properties of a panel of dodecasaccharides (12-mers) with varying sulfation patterns in healthy mice and uncover the pharmacokinetic properties of an octadecasaccharide (18-mer) in acutely injured mice. In the 12-mer panel, 1 12-mer, known as dekaparin, is anticoagulant, and 3 12-mers are nonanticoagulant. The concentrations of 12-mers in plasma and urine were determined by the disaccharide analysis using liquid chromatography coupled with tandem mass spectrometry. We observed a striking difference between anticoagulant and nonanticoagulant oligosaccharides in the 12-mer panel, showing that anticoagulant dekaparin had a 4.6-fold to 8.6-fold slower clearance and 4.4-fold to 8-fold higher plasma exposure compared to nonanticoagulant 12-mers. We also observed that the clearance of HS oligosaccharides is impacted by disease. Using an antiinflammatory 18-mer, we discovered that the clearance of 18-mer is reduced 2.8-fold in a liver failure mouse model compared to healthy mice. Our results suggest that oligosaccharides are rapidly cleared renally if they have low interaction with circulating proteins. We observed that the clearance rate of oligosaccharides is inversely associated with the degree of binding to target proteins, which can vary in response to pathophysiological conditions. Our findings uncover a contributing factor for the plasma and renal clearance of oligosaccharides which will aid the development of HS-based therapeutics.
Elucidation of the O-antigen structure of Escherichia coli O93 and characterization of its biosynthetic genes
Authors: Furevi Axel , Ståhle Jonas , Muheim Claudio , Gkotzis Spyridon , Daley Daniel O , Udekwu Klas I , Widmalm Göran 
Published: October 2022

Abstract
The structure of the O-antigen from the international reference strain Escherichia coli O93:−:H16 has been determined. A nonrandom modal chain-length distribution was observed for the lipopolysaccharide, a pattern which is typical when long O-specific polysaccharides are expressed. By a combination of (i) bioinformatics information on the gene cluster related to O-antigen synthesis including putative function on glycosyl transferases, (ii) the magnitude of NMR coupling constants of anomeric protons, and (iii) unassigned 2D 1H, 13C-HSQC, and 1H,1H-TOCSY NMR spectra it was possible to efficiently elucidate the structure of the carbohydrate polymer in an automated fashion using the computer program CASPER. The polysaccharide also carries O-acetyl groups and their locations were determined by 2D NMR experiments showing that ~½ of the population was 2,6-di-O-acetylated, ~¼ was 2-O-acetylated, whereas ~¼ did not carry O-acetyl group(s) in the 3-O-substituted mannosyl residue of the repeating unit. The structure of the tetrasaccharide repeating unit of the O-antigen is given by: →2)-β-d-Manp-(1→3)-β-d-Manp2Ac6Ac-(1→4)-β-d-GlcpA-(1→3)-α-d-GlcpNAc-(1→, which should also be the biological repeating unit and it shares structural elements with capsular polysaccharides from E. coli K84 and K50. The structure of the acidic O-specific polysaccharide from Cellulophaga baltica strain NN015840T differs to that of the O-antigen from E. coli O93 by lacking the O-acetyl group at O6 of the O-acetylated mannosyl residue.
Effects of Taurine in Mice and Zebrafish Behavioral Assays With Translational Relevance to Schizophrenia
Authors: Giongo Franciele Kich , Gallas-Lopes Matheus , Benvenutti Radharani , Sachett Adrieli , Bastos Leonardo Marensi , Rosa Adriane Ribeiro , Herrmann Ana Paula 
Published: October 2022

Abstract

Background
Altered redox state and developmental abnormalities in glutamatergic and GABAergic transmission during development are linked to the behavioral changes associated with schizophrenia. As an amino acid that exerts antioxidant and inhibitory actions in the brain, taurine is a potential candidate to modulate biological targets relevant to this disorder. Here, we investigated in mice and zebrafish assays whether taurine prevents the behavioral changes induced by acute administration of MK-801 (dizocilpine), a glutamate N-methyl-D-aspartate (NMDA) receptor antagonist.

Methods
C57BL/6 mice were i.p. administered with saline or taurine (50, 100, and 200 mg/kg) followed by MK-801 (0.15 mg/kg). Locomotor activity, social interaction, and prepulse inhibition of the acoustic startle reflex were then assessed in different sets of animals. Zebrafish were exposed to tank water or taurine (42, 150, and 400 mg/L) followed by MK-801 (5 µM); social preference and locomotor activity were evaluated in the same test.

Results
MK-801 induced hyperlocomotion and disrupted sensorimotor gating in mice; in zebrafish, it reduced sociability and increased locomotion. Taurine was mostly devoid of effects and did not counteract NMDA antagonism in mice or zebrafish.

Discussion
Contradicting previous clinical and preclinical data, taurine did not show antipsychotic-like effects in the present study. However, it still warrants consideration as a preventive intervention in animal models relevant to the prodromal phase of schizophrenia; further studies are thus necessary to evaluate whether and how taurine might benefit patients.
HIV RNA Screening Reduces Integrase Strand Transfer Inhibitor Resistance Risk in Persons Receiving Long-Acting Cabotegravir for HIV Prevention
Authors: Eshleman Susan H , Fogel Jessica M , Halvas Elias K , Piwowar-Manning Estelle , Marzinke Mark A , Kofron Ryan , Wang Zhe , Mellors John , McCauley Marybeth , Rinehart Alex R , St Clair Marty , Adeyeye Adeola , Hinojosa Juan C , Cabello Robinson , Middelkoop Keren , Hanscom Brett , Cohen Myron S , Grinsztejn Beatriz , Landovitz Raphael J ,   HPTN 083 Study Team, Seisa Michael , Lie Yolanda , Meyer William , Marrazzo Jeanne , Peel Sheila , Wallis Carole , Asmelash Aida , Daar Eric , Rooney James , Clark Richard 
Published: October 2022

Abstract

Background
The HPTN 083 trial demonstrated that long-acting cabotegravir (CAB-LA) was superior to tenofovir-disoproxil fumarate/emtricitabine for human immunodeficiency virus (HIV) preexposure prophylaxis (PrEP). Integrase strand transfer inhibitor (INSTI) resistance-associated mutations (RAMs) were detected in some participants with HIV infection. We used a low viral load INSTI genotyping assay to evaluate the timing of emergence of INSTI RAMs and assessed whether HIV screening with a sensitive RNA assay would have detected HIV infection before INSTI resistance emerged.

Methods
Single-genome sequencing to detect INSTI RAMs was performed for samples with viral loads &lt;500 copies/mL from 5 participants with previously identified INSTI RAMs and 2 with no prior genotyping results.

Results
Major INSTI RAMs were detected in all 7 cases. HIV RNA testing identified infection before major INSTI RAMs emerged in 4 cases and before additional major INSTI RAMs accumulated in 1 case. Most INSTI RAMs were detected early when the viral load was low and CAB concentration was high.

Conclusions
When using CAB-LA PrEP, earlier detection of HIV infection with a sensitive RNA assay may allow for earlier treatment initiation with the potential to reduce INSTI resistance risk. Further studies are needed to evaluate the value and feasibility of HIV RNA testing with CAB-LA PrEP.