bluuebunny/crossref_metadata_2025_split huggingface dataset:
Long-term mayor adverse cardiovascular events after COVID-19 infection: a clinical score from a cohort of 2575 patients enrolled in the multicenter international HOPE 2 registry
Authors: Santoro F , Di Nunno N , Centola A , Cetera R , Le Rose V , Perez-Villacastin J , Fernandez-Ortiz A , Nunez Gil I , Brunetti N D 
Published: October 2022

Abstract

Background
Long-term consequences of COVID-19 infection are still partly known. According to some studies several patients may experience long term symptoms; however, predictors of long-term mayor adverse cardiovascular events among (MACE) patients with previous COVID-19 infection are .

Aim of the study
To derive a simple clinical score for risk prediction of long-term MACE among patients with previous covid-19 infection.

Methods
2575 consecutive patients were enrolled in a multicenter, international registry (HOPE-2) from February 2020 to April 2021, and followed-up at long-term. A risk score was developed using a stepwise multivariable regression analysis.

Results
Out of 2575 patients enrolled in the HOPE-2 registry, 1481 (58%) were male, with mean age of 60±16 years. At long-term follow-up overall rate of MACE was 7.9% (202 of 2545 pts, 3.3% death, 2.4% inflammatory myocardial disease, 1.3% arterial thrombosis, 0.7% venous thrombosis). After multivariable regression analysis, independent predictors of MACE were used to derive a simple prognostic score: The HOPE-2 prognostic score may be calculated by giving: ½ point for every 10 years of age, 2 points for previous cardiovascular disease, 1 point for increased troponin serum levels during hospitalization, 2.5 points for heart failure and 3 points for sepsis during hospitalization, −1.5 points for vaccination at follow-up. Score accuracy at receiver operating characteristic curve analysis was 0.81.
Stratification into 3 risk groups (0–2, 3–5, and &gt;5 points) classified into low, intermediate and high risk. The observed MACE rates were 0.5% for low-risk patients, 4% for intermediate-risk patients, and 19.5% for high-risk patients (log-Rank p&lt;0.001, Figure 1).

Conclusions
The HOPE-2 prognostic score may be useful for long-term risk stratification in patients with previous COVID-19 infection. High-risk patients may require a strict cardiological follow-up.

Funding Acknowledgement
Type of funding sources: None.
Performance of high-sensitivity cardiac troponin T versus I for the early diagnosis of myocardial infarction
Authors: Koechlin L , Boeddinghaus J , Lopez-Ayala P , Nestelberger T , Miro O , Wussler D , Zimmermann T , Strebel I , Christ M , Wildi K , Rubini Gimenez M , Martin-Sanchez J , Keller D , Twerenbold R , Mueller C 
Published: October 2022

Abstract

Background
Clinical practice guidelines assume that both cardiac troponin (cTn) T and cTnI concentrations reflect identical pathophysiological processes and are equally effective in the detection of myocardial injury. However, there are differences between cTnT and cTnI that have been reported.

Purpose
The aim of this study was to directly compare the diagnostic performance of high-sensitivity cardiac troponin (hs-cTn) T versus hs-cTnI for the early diagnosis of acute myocardial infarction (MI).

Methods
In a prospective multicentre study, diagnostic and prognostic accuracies of hs-cTnT and I were analyzed in consecutive patients presenting to the emergency department with acute chest pain. The final diagnosis was adjudicated by two independent cardiologists using all information pertaining to the individual patient according to the fourth universal definition of MI. Adjudication of the final diagnoses was performed twice: once using serial measurements of hs-cTnT and once using hs-cTnI. Furthermore, the clinical performance of hs-cTnT/I when embedded in the European Society of Cardiology (ESC) 0/1h-algorithm was assessed.

Results
Among 5087 consecutive patients (median [Interquartile range, IQR] age 61 [49.0, 74.0] years, 33.2% female), 951 (18.7%) and 901 patients (17.7%) had an adjudicated final diagnosis of non-ST-segment elevation myocardial infarction (NSTEMI) when using serial measurements of hs-cTnT and hs-cTnI for adjudication, respectively. Diagnostic accuracy was very high for both hs-cTnT and hs-cTnI and comparable when using hs-cTnT for adjudication (hs-cTnT: area under the curve [AUC] 0.93 [95% CI 0.92–0.94] versus hs-cTnI AUC 0.93 [95% CI 0.92–0.94]; p=0.891). However, when using serial measurements of hs-cTnI for adjudication, diagnostic accuracy was significantly higher for hs-cTnI (AUC 0.93 [95% CI 0.92–0.94] versus AUC 0.94 [95% CI 0.94–0.95], p&lt;0.001; Figure 1). This was confirmed in subgroup analyses including early presenter (≤3h), patients with renal failure, known coronary artery disease and elderly (≥70 years). However, both assays performed excellent with very high safety for rule-out and high accuracy for rule-in MI when embedded in the ESC 0/1h-algorithm. Prognostic accuracies for 730-day all-cause mortality and cardiovascular death were significantly higher for hs-cTnT compared to hs-cTnI (Figure 2).

Conclusions
While there seem to be differences between hs-cTnT and hs-cTnI in their diagnostic and prognostic performance, clinical relevance needs to be further evaluated since both assays performed excellent when embedded in their respective early triage algorithms.

Funding Acknowledgement
Type of funding sources: Foundation. Main funding source(s): Swiss National Foundation, Swiss Heart Foundation
Differences in circulating cardiac troponin I and T in acute and chronic cardiac disease
Authors: Zimmermann T , Koechlin L , Walter J , Kimenai D , Nestelberger T , Boeddinghaus J , Lopez-Ayala P , Puelacher C , Gualandro D , Strebel I , Diebold M , Twerenbold R , Hammarsten O , Meex S , Mueller C 
Published: October 2022

Abstract

Background
Clinical practice and guidelines assume that cardiac troponin I (cTnI) and cTnT are interchangeable, reflecting identical pathophysiological processes. However, it is unknown if cTnI and cTnT really are equivalent measures in different pathophysiological settings.

Purpose
To highlight potential differences in the release of cTnI and cTnT.

Methods
Large pooled cohort analysis including extensively characterized individuals, stratified into three groups: no cardiac disease (normal aging), chronic cardiac disease, and acute cardiac disease. Circulating cTnI and cTnT concentrations were measured blinded to clinical data using high-sensitivity assays (hs-cTnI-Architect, hs-cTnT-Elecsys) and their ratio calculated. Findings were validated using a second hs-cTnI assay (hs-cTnI-Clarity).

Results
Among 8719 individuals, 29% female, 10% had no known cardiac disease, 71% chronic cardiac disease, and 20% acute cardiac disease. Baseline characteristics including renal function were comparable between individuals with chronic and acute cardiac disease. Normal aging (without cardiac disease) was associated with a disproportional increase in cTnT versus cTnI (low cTnI/cTnT ratio, median 0.50, IQR 0.38–0.68). Although older, patients with chronic cardiac disease had a slightly higher cTnI/cTnT ratio (median 0.53, IQR 0.37–0.79, p&lt;0.05). In contrast, in patients with acute cardiac disease, cTnI concentrations were disproportionally elevated compared to cTnT concentrations, resulting in a cTnI/cTnT ratio of 1.96 (IQR 0.93–4.73, p&lt;0.001). Internal validation using a second hs-cTnI assay confirmed these findings.

Conclusion
These findings suggest relevant differences in the release of cTnI and cTnT with a greater release of cTnT versus cTnI in normal aging and a disproportional increase in cTnI versus cTnT in acute cardiac disease.

Funding Acknowledgement
Type of funding sources: Foundation. Main funding source(s): Swiss National Science Foundation
Agreement between four high-sensitivity cardiac troponin assays and non-invasive testing, clinical and quality of care outcomes based on the 2020 ESC guidelines: results from the ROMICAT II trial
Authors: Karady J , Mayrhofer T , Nagurney J T , Udelson J E , Fleg J L , Peacock W F , Januzzi J L , Koenig W , Ferencik M , Hoffmann U 
Published: October 2022

Abstract

Background
Quality of care and safety of patients with suspected acute coronary syndrome (ACS) would greatly benefit if management was independent of which high-sensitivity cardiac troponin (hs-cTn) assay was used for risk stratification.

Purpose
To assess the agreement of 4 hs-cTn assays to risk stratify patients with suspected ACS using the ESC2020 Guidelines 0/2-hour algorithm, and to assess their associations with non-invasive diagnostic testing, clinical- and quality of care outcomes.

Methods
We analyzed blood samples obtained at emergency department (ED) presentation and 2 hours later from patients with suspected ACS enrolled in the ROMICAT (Rule Out Myocardial Infarction/Ischemia Using Computer Assisted Tomography) II trial, using 4 hs-cTn assays (Roche Diagnostics, Elecsys 2010; Abbott Diagnostics, ARCHITECT i2000SR; Siemens Diagnostics, HsVista; Beckman Coulter, ACCESS). We determined the agreement between the assays to assign patients to rule-out, observe, and rule-in management pathways according to the ESC2020 Guidelines. Further, we assessed assay association with non-invasive diagnostic test findings and adjudicated clinical- and quality of care outcomes. Finally, we compared observed conventional troponin management with predicted management per ESC2020 guidelines using hs-cTn assays.

Results
Overall, assignment to ESC2020 Guideline management pathways among 238 patients with suspected ACS (age 52.7±8.0 years; 40.3% [96/238] female) was concordant across all hs-Tn assays in 74% of patients but differed for rule-out rates (89.9% vs 76.5% vs 78.6% vs 86.6%, p&lt;0.001) and observation rates (6.7% vs 20.6% vs 17.7% vs 9.2%, p&lt;0.001), but not for rule-in (3.4% vs 2.9% vs 3.8% vs 4.2%, p=0.623). Among those whose management recommendation was rule-out, 19.1–21.6% had obstructive CAD defined as coronary stenosis ≥50% on coronary CT angiography or inducible myocardial ischemia on perfusion imaging and 3.3–4.2% were diagnosed with ACS as adjudicated by independent panel. Predicted ED discharge rates based on hs-cTn assays were higher than those observed with conventional troponin (80.3% to 90.8% vs. 21.0%, respectively p&lt;0.001). As a result, predicted costs of care were significantly lower based on strategies utilizing hs-cTn assays than with conventional troponin ($2,578±2,896 to $2,894±4,371 vs $3,889±4,833, respectively, p&lt;0.001)

Conclusion
In a quarter of patients presenting to the ED with suspected ACS ESC2020 Guideline-based management may be different, depending on the hs-cTn assay. As compared to conventional troponin, hs-cTn is predicted to significantly increase direct ED discharges and lower costs of care.

Funding Acknowledgement
Type of funding sources: None.
An altered balance of plasma arginine metabolites is associated with increased thickness of the coronary intima-media complex in the adjacent to the culprit segment of an infarct-related artery
Authors: Molek P , Zmudzki P , Machnik A , Nowak G , Wnuk M , Wlodarczyk A , Nessler J , Zalewski J 
Published: October 2022

Abstract

Background
The biomarkers of atherosclerosis remain insufficiently understood.

Purpose
We sought to investigate whether an altered balance of arginine metabolites in patients following myocardial infarction (MI) is associated with remodeling of the adjacent to the culprit segments of an infarct-related artery (IRA) and with clinical outcomes.

Methods
Arginine and its metabolites including ornithine, citrulline, proline and asymmetric dimethylarginine were measured using liquid chromatography and tandem mass spectrometry in 85 consecutive ST-segment elevation MI patients upon admission and at 6-month follow-up and were compared with morphology of the adjacent to the culprit proximal and distal 10-mm segments of IRA assessed with optical coherence tomography. A composite ischemic event was defined as death, recurrent MI, stroke, or unplanned percutaneous coronary intervention.

Results
The ratios of citrulline/ornithine and citrulline/arginine decreased 5.22 and 2.20 times (both P&lt;0.001) respectively, while the ornithine/arginine index (I_O/A) increased 2.96 times (P&lt;0.001) following ischemia compared with stable follow-up, indicating the enhanced arginase activity over nitric oxide synthase (NOS) in acute phase of STEMI. Follow-up I_O/A correlated with the mean intima-media (R=0.34, P=0.003, Figure 1A) and intima (R=0.30, P=0.008) diameter of an adjacent to the culprit IRA segment. By multivariate analysis, apart from male gender (P&lt;0.001) and diabetes mellitus (P=0.02), a higher follow-up I_O/A was associated with the larger mean intima-media diameter of an adjacent to the culprit IRA segments (coefficient 0.218, 95% confidence interval 0.040–0.397, P=0.017, per 0.01). Within the median follow-up of 25 (19–35) months, ischemic composite endpoint was found in 13 (15.3%) patients. The follow-up I_O/A reached the area under the ROC curve of 0.78 (95% confidence interval 0.66–0.91, P=0.005) for prediction of composite ischemic endpoint with a cut-off value of ≥0.57, and a sensitivity of 72.3% and specificity of 80.0% (Figure !B).

Conclusions
Our findings provide arguments that during the acute phase of MI, arginine metabolism is shifted from NOS towards arginase, as compared to 6-month stable conditions. Simultaneously, the enhanced residual arginase activity over NOS in chronic phase was correlated with a higher thickness of intima or intima-media in the adjacent to the culprit segment within the IRA, and was also associated with unfavorable clinical outcomes.

Funding Acknowledgement
Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Grant of the National Science Center of Poland (Number 2016/21/B/NZ5/01378 to J.Z.)
Validation of a novel high-sensitivity cardiac troponin assay
Authors: Restan I , Steiro O T , Tjora H L , Langoergen J , Omland T , Collinson P , Bjoerneklett R , Vikenes K , Steinsvik T , Skadberg O , Mjelva O R , Larsen A I , Bonarjee V S , Aakre K M 
Published: October 2022

Abstract

Background
The accuracy for early identification of non-ST-elevation myocardial infarction (NSTEMI) in the emergency department must be determined for all novel high-sensitivity cardiac troponin assays (hs-cTn). In this prospective, multi-centre study we developed rule-out algorithms for a high-sensitivity cardiac troponin I (hs-cTnI) assay and compared it to established algorithms for hs-cTnT and hs-cTnI.

Methods
Two rule-out algorithms for NSTEMI were developed from a derivation cohort of 977 patients assessed by the Siemens Atellica IM hs-cTnI assay. Diagnostic performance was compared with hs-cTnT (Roche) and hs-cTnI (Abbott) algorithms. The derived algorithms were tested in two different validation cohorts (n=518 and n=405, respectively).

Results
An admission sample algorithm (hs-cTnI (Siemens)) for rule-out of NSTEMI with cutoff &lt;5 ng/L had negative predictive value (NPV) 99.4–100.0%, sensitivity 98.3–100% and specificity 46.7–56.5% in the two validation cohorts. Sensitivity and NPV was similar, specificity trended towards improvement over the comparator algorithms (Figure 1).
A 0–1 hour algorithm (hs-cTnI (Siemens)) with cutoff &lt;10 ng/L and Δ change &lt;3 ng/L achieved sensitivity and NPV 100% with specificity &gt;70% in both validation cohorts, similar to the comparator algorithms (Table 1).

Conclusions
Rule-out algorithms from the Siemens Atellica hs-cTnI assay has comparable diagnostic accuracy to established hs-cTn rule-out algorithms.

Funding Acknowledgement
Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Public grant: Western Norway Regional Health Authority.Private company funding: Siemens Healthineers AG
Effectiveness of antitussives, anticholinergics, and honey versus usual care in adults with uncomplicated acute bronchitis: a multiarm randomized clinical trial
Authors: Llor Carl , Moragas Ana , Ouchi Dan , Monfà Ramon , Garcia-Sangenís Ana , Gómez-Lumbreras Ainhoa , Pera Helena , Pujol Jesus , Morros Rosa 
Published: October 2022

AbstractBackgroundDespite the frequent use of symptomatic therapies in cough, evidence of their benefits is lacking.ObjectiveWe compared the effectiveness of 3 symptomatic therapies and usual care in acute bronchitis.MethodsMulticenter, pragmatic, multiarm parallel group, open randomized trial in primary care (ClinicalTrials.gov, Identifier: NCT03738917) was conducted in Catalonia. Patients ≥18 with uncomplicated acute bronchitis, with cough&lt;3 weeks as the main symptom, scoring ≥4 in either daytime or nocturnal cough (7-point Likert scale), were randomized to usual care, dextromethorphan 15 mg t.i.d., ipratropium bromide inhaler 20 µg 2 puffs t.i.d, or 30 mg of honey t.i.d., all taken for up to 14 days. The main outcome measure was the number of days with moderate-to-severe cough. A symptom diary was given. A second visit was scheduled at days 2–3 for assessing evolution, with 2 more visits at days 15 and 29 for clinical assessment, evaluation of adverse effects, re-attendance, and complications.ResultsWe failed to achieve the sample size scheduled due to the COVID-19 pandemic. We finally recruited 194 patients. The median number of days with moderate-to-severe cough (score ≥ 3) in the usual care arm was 5 (interquartile range [IQR], 4, 8.75), 5 in the ipratropium bromide arm (IQR, 3, 8), 5 in the dextromethorphan arm (IQR, 4, 9.75), and 6 in the honey arm (IQR, 3.5, 7). The same results were obtained in the Kaplan–Meier survival analysis for the median survival time of each arm with the usual care as the reference group.ConclusionThe symptomatic treatment evaluated has shown to be ineffective against cough.
Microseismic data denoising in the sychrosqueezed domain by integrating the wavelet coefficient thresholding and pixel connectivity
Authors: Zeng Zhiyi , Lu Tianxin , Han Peng , Zhang Da , Yang Xiao-Hui , Shi Yaqian , Chang Ying , Zhang Jianzhong , Dai Rui , Ji Hu 
Published: October 2022

SUMMARY
Microseismic monitoring is crucial for risk assessment in mining, fracturing and excavation. In practice, microseismic records are often contaminated by undesired noise, which is an obstacle to high-precision seismic locating and imaging. In this study, we develop a new denoising method to improve the signal-to-noise ratio (SNR) of seismic signals by combining wavelet coefficient thresholding and pixel connectivity thresholding. First, the pure background noise range in the seismic record is estimated using the ratio of variance (ROV) method. Then, the synchrosqueezed continuous wavelet transform (SS-CWT) is used to project the seismic records onto the time–frequency plane. After that, the wavelet coefficient threshold for each frequency is computed based on the empirical cumulative distribution function (ECDF) of the coefficients of the pure background noise. Next, hard thresholding is conducted to process the wavelet coefficients in the time–frequency domain. Finally, an image processing approach called pixel connectivity thresholding is introduced to further suppress isolated noise on the time–frequency plane. The wavelet coefficient threshold obtained by using pure background noise data is theoretically more accurate than that obtained by using the whole seismic record, because of the discrepancy in the power spectrum between seismic waves and background noise. After hard thresholding, the wavelet coefficients of residual noise exhibit isolated and lower pixel connectivity in the time–frequency plane, compared with those of seismic signals. Thus, pixel connectivity thresholding is utilized to deal with the residual noise and further improve the SNR of seismic records. The proposed new denoising method is tested by synthetic and real seismic data, and the results suggest its effectiveness and robustness when dealing with noisy data from different acquisition environments and sampling rates. The current study provides a useful tool for microseismic data processing.
NRSF regulates age-dependently cognitive ability and its conditional knockout in APP/PS1 mice moderately alters AD-like pathology
Authors: Yang Yufang , Zhang Xiaoshuang , Li Dongxue , Fang Rong , Wang Zishan , Yun Di , Wang Mo , Wang Jinghui , Dong Hongtian , Fei Zhaoliang , Li Qing , Liu Zhaolin , Shen Chenye , Fei Jian , Yu Mei , Behnisch Thomas , Huang Fang 
Published: October 2022

Abstract
NRSF/REST (neuron-restrictive silencer element, also known as repressor element 1-silencing transcription factor), plays a key role in neuronal homeostasis as a transcriptional repressor of neuronal genes. NRSF/REST relates to cognitive preservation and longevity of humans, but its specific functions in age-dependent and Alzheimer’s disease (AD)-related memory deficits remain unclear. Here, we show that conditional NRSF/REST knockout either in the dorsal telencephalon or specially in neurons induced an age-dependently diminished retrieval performance in spatial or fear conditioning memory tasks and altered hippocampal synaptic transmission and activity-dependent synaptic plasticity. The NRSF/REST deficient mice were also characterized by an increase of activated glial cells, complement C3 protein and the transcription factor C/EBPβ in the cortex and hippocampus. Reduction of NRSF/REST by conditional depletion upregulated the activation of astrocytes in APP/PS1 mice, and increased the C3-positive glial cells, but did not alter the Aβ loads and memory retrieval performances of 6- and 12-month-old APP/PS1 mice. Simultaneously, overexpression of NRSF/REST improved cognitive abilities of aged wild type, but not in AD mice. These findings demonstrated that NRSF/REST is essential for the preservation of memory performance and activity-dependent synaptic plasticity during aging and takes potential roles in the onset of age-related memory impairments. However, while altering the glial activation, NRSF/REST deficiency does not interfere with the Aβ deposits and the electrophysiological and cognitive AD-like pathologies.
The effect on women’s health of extending parental leave: a quasi-experimental registry-based cohort study
Authors: Courtin Emilie , Rieckmann Andreas , Bengtsson Jessica , Nafilyan Vahe , Melchior Maria , Berkman Lisa , Hulvej Rod Naja 
Published: October 2022

Abstract

Background
Parental leave policies have been hypothesized to benefit mothers’ mental health. We assessed the impact of a 6-week extension of parental leave in Denmark on maternal mental health.

Methods
We linked individual-level data from Danish national registries on maternal sociodemographic characteristics and psychiatric diagnoses. A regression discontinuity design was applied to study the increase in parental leave duration after 26 March 1984. We included women who had given birth between 1 January 1981 and 31 December 1987. Our outcome was a first psychiatric diagnosis following the child’s birth, ascertained as the first day of inpatient hospital admission for any psychiatric disorder. We presented cumulative incidences for the 30-year follow-up period and reported absolute risk differences between women eligible for the reform vs not, in 5-year intervals.

Results
In all, 291 152 women were followed up until 2017, death, emigration or date of first psychiatric diagnosis. The median follow-up time was 29.99 years, corresponding to 10 277 547 person-years at risk. The cumulative incidence of psychiatric diagnoses at 30 years of follow-up was 59.5 (95% CI: 57.4 to 61.6) per 1000 women in the ineligible group and 57.5 (95% CI: 55.6 to 59.4) in the eligible group. Eligible women took on average 32.85 additional days of parental leave (95% CI: 29.20 to 36.49) and had a lower probability of having a psychiatric diagnosis within 5 years [risk difference (RD): 2.4 fewer diagnoses per 1000 women, 95% CI: 1.5 to 3.2] and up to 20 years after the birth (RD: 2.3, 95% CI: 0.4 to 4.2). In subgroup analyses, the risk reduction was concentrated among low-educated, low-income and single women.

Conclusions
Longer parental leave may confer mental health benefits to women, in particular to those from disadvantaged backgrounds.