Abstract
Dual antiplatelet therapy has long been the standard of care in preventing coronary and cerebrovascular thrombotic events in patients with chronic coronary syndrome and acute coronary ...syndrome undergoing percutaneous coronary intervention, but choosing the optimal treatment duration and composition has become a major challenge. Numerous studies have shown that certain patients benefit from either shortened or extended treatment duration. Furthermore, trials evaluating novel antithrombotic strategies, such as P2Y12 inhibitor monotherapy, low-dose factor Xa inhibitors on top of antiplatelet therapy, and platelet function- or genotype-guided (de-)escalation of treatment, have shown promising results. Current guidelines recommend risk stratification for tailoring treatment duration and composition. Although several risk stratification methods evaluating ischaemic and bleeding risk are available to clinicians, such as the use of risk scores, platelet function testing , and genotyping, risk stratification has not been broadly adopted in clinical practice. Multiple risk scores have been developed to determine the optimal treatment duration, but external validation studies have yielded conflicting results in terms of calibration and discrimination and there is limited evidence that their adoption improves clinical outcomes. Likewise, platelet function testing and genotyping can provide useful prognostic insights, but trials evaluating treatment strategies guided by these stratification methods have produced mixed results. This review critically appraises the currently available antithrombotic strategies and provides a viewpoint on the use of different risk stratification methods alongside clinical judgement in current clinical practice.
Graphical Abstract
To determine the clinical efficacy, adverse events and side-effect dyspnea of
and CYP3A5 expressor status in ticagrelor treated patients.
Ticagrelor treated patients from the POPular Genetics ...randomized controlled trial were genotyped for
and
alleles. Patients were divided based on their genotype. In total 1,281 patients with ST-segment elevation myocardial infarction (STEMI) were included.
carriers (
= 152)
non-carrier status (
= 1,129) were not found to have a significant correlation with the primary thrombotic endpoint: cardiovascular death, myocardial infarction, definite stent thrombosis and stroke 1.3% vs. 2.5%, adjusted hazard ratio 1.81 (0.43-7.62)
, or the primary bleeding endpoint: PLATO major and minor bleeding 13.2% vs. 11.3%, adjusted hazard ratio 0.93 (0.58-1.50)
. Among the
patients, CYP3A5 expressors (
= 196)
non-expressors (
= 926) did not show a significant difference for the primary thrombotic 2.6% vs. 2.5%, adjusted hazard ratio 1.03 (0.39-2.71)
, or the primary bleeding endpoint 12.8% vs. 10.9%, adjusted hazard ratio 1.13 (0.73-1.76)
. With respect to dyspnea, no significant difference was observed between
carriers
non-carriers 44.0% vs. 45.0%, odds ratio 1.04 (0.45-2.42)
, or in the
group, CYP3A5 expressors
CYP3A5 non-expressors 35.3% vs. 47.8%, odds ratio 0.60 (0.27-1.30)
.
In STEMI patients treated with ticagrelor, neither the
carriers, nor the CYP3A5 expressor status had a statistical significant effect on thrombotic and bleeding event rates nor on dyspnea.
ClinicalTrials.gov, identifier NCT01761786.
Summary
Background
Port‐wine stain (PWS) is a vascular malformation characterized by progressive dilatation of postcapillary venules, but the molecular pathogenesis remains obscure.
Objectives
To ...illustrate that PWS endothelial cells (ECs) present a unique molecular phenotype that leads to pathoanatomical PWS vasculatures.
Methods
Immunohistochemistry and transmission electron microscopy were used to characterize the ultrastructure and molecular phenotypes of PWS blood vessels. Primary culture of human dermal microvascular endothelial cells and in vitro tube formation assay were used for confirmative functional studies.
Results
Multiple clinicopathological features of PWS blood vessels during the development and progression of the disease were shown. There were no normal arterioles and venules observed phenotypically and morphologically in PWS skin; arterioles and venules both showed differentiation impairments, resulting in a reduction of arteriole‐like vasculatures and defects in capillary loop formation in PWS lesions. PWS ECs showed stemness properties with expression of endothelial progenitor cell markers CD133 and CD166 in non‐nodular lesions. They also expressed dual venous/arterial identities, Eph receptor B1 (EphB1) and ephrin B2 (EfnB2). Co‐expression of EphB1 and EfnB2 in normal human dermal microvascular ECs led to the formation of PWS‐like vasculatures in vitro, for example larger‐diameter and thick‐walled capillaries.
Conclusions
PWS ECs are differentiation‐impaired, late‐stage endothelial progenitor cells with a specific phenotype of CD133+/CD166+/EphB1+/EfnB2+, which form immature venule‐like pathoanatomical vasculatures. The disruption of normal EC–EC interactions by coexistence of EphB1 and EfnB2 contributes to progressive dilatation of PWS vasculatures.
What's already known about this topic?
Port‐wine stain (PWS) is a congenital progressive vascular malformation of human skin.
Vascular lesions are considered as dilation of postcapillary venules in PWS.
Pathological alterations involving the entire physiological milieu of skin are present in the early stage of PWS.
What does this study add?
PWS endothelial cells (ECs) are differentiation‐impaired, late‐stage endothelial progenitor cells (EPCs) with a phenotype of CD133+/CD166+/Eph receptor B1 (EphB1)+/ephrin B2 (EfnB2)+.
PWS blood vessels are immature venule‐like pathoanatomical vasculatures.
Coexistence of EphB1 and EfnB2 in PWS ECs contributes to the progressive dilatation of PWS vasculatures.
What is the translational message?
PWS EPCs are the major contributor to the angiogenesis of PWS blood vessels after pulsed‐dye laser therapy.
The surface markers EphB1, EfnB2, CD133 and CD166 provide a molecular basis for specific targeting of PWS EPCs.
Blockage of EphB1/EfnB2 signalling may promote PWS EPC differentiation and inhibit progressive dilatation of PWS vasculatures.
Linked Comment: Fear. Br J Dermatol 2017; 177:1478–1479.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Advanced atrial fibrillation (AF) patients have persistent AF, failed previous catheter ablation and/or an enlarged left atrium (LA), which is associated with a reduced success of AF ablation. ...Transthoracic echocardiography (TTE) and contrast enhanced magnetic resonance angiography (CE-MRA) are available to assess LA volume. However, it is unknown how these modalities relate in patients with advanced AF. We therefore compared the reproducibility of TTE and non-triggered CE-MRA in advanced AF patients and their ability to select patients with successful thoracoscopic AF ablation.
Two independent observers measured LA volumes on 65 TTE and CE-MRA exams of advanced AF patients prior to AF ablation. Patients were followed after AF ablation with rhythm monitoring every 3 months for 1 year to determine AF recurrence. Inter-modality, inter- and intra-observer variability were determined using intraclass correlation coefficients (ICC). Receiver-operating characteristic (ROC) analysis was performed to determine sensitivity and specificity of TTE and CE-MRA volume and CE-MRA dimensions to identify patients with AF recurrence during follow-up.
LA enlargement ≥ 34 ml/m
was present in 60% of the patients. CE-MRA and TTE demonstrated a good correlation for LA volume assessment (intraclass correlation, ICC = 0.86; p < 0.001) with larger volumes consistently measured by CE-MRA. Major discrepancies were mostly attributed to TTE acquisition. Craniocaudal enlargement discriminated patients with AF recurrence (AUC 0.67 95% CI 0.55-0.85, p = 0.01).
Non-triggered CE-MRA is a viable and reproducible 3D alternative for 2D TTE to assess LA volume in advanced AF patients. Craniocaudal enlargement was the only discriminator of AF recurrence after AF ablation.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The aim of this meta‐analysis was to evaluate the effect of telephone‐based interventions on prognostic outcomes and health‐related quality of life (HRQoL) in breast cancer patients and survivors. A ...systematic search of the Cochrane Library, Web of science, Medline, EMBASE, CNKI and CBM database was carried out. Randomised, controlled trials (RCTs) examining the effects of telephone‐based intervention versus a control group receiving no telephone intervention, on prognostic outcomes and HRQoL with breast cancer were included. A meta‐analysis was conducted to quantify the effects of telephone‐based interventions on anxiety, depression, fatigue, self‐efficiency, physiological function, social‐domestic function and quality of life. In total, 14 studies involving 2002 participants were included. Due to the effect of telephone‐based interventions, statistically significant results were found on anxiety (standard mean difference SMD = −0.16, 95% confidence intervals CI 0.01, 0.30, p = .04), self‐efficiency (SMD = 0.22, 95% CI −0.34, −0.10, p = .0004), social‐domestic function (SMD = 0.19, 95% CI −0.35, −0.03, p = .02) and quality of life (SMD = 0.54, 95% CI −1.00, −0.08, p = .02). Although the effects on depression, fatigue and physiological function were in the expected direction, these effects were not statistically significant (p > .05) based on the insufficient evidence.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Background
Guidelines recommend prasugrel or ticagrelor for acute coronary syndrome (ACS) patients. However, these P2Y12 inhibitors increase bleeding risk compared to clopidogrel. Although ...genotype-guided P2Y12-inhibitor selection has been shown to reduce bleeding risk, data on its clinical implementation is lacking.
Methods
The study included ACS patients receiving genotype-guided antiplatelet therapy, utilising either a point-of-care (POC) device or laboratory-based testing. We aimed to collect qualitative and quantitative data on genotyping, eligibility for de-escalation, physician adherence to genotype results, time to de-escalation and cost reduction.
Results
Of the 1,530 patients included in the ACS registry from 2021 to 2023, 738 ACS patients treated with ticagrelor received a CYP2C19 genotype test. The median turnover time of genotyping was 6.3 hours (interquartile range IQR, 3.2-16.7), with 82.3% of the genotyping results known within 24 hours after admission. POC genotyping exhibited significantly shorter turnaround times compared to laboratory-based testing (with respective medians of 5.7 vs 47.8 hours; P < .001). Of the genotyped patients, 81.7% were eligible for de-escalation which was carried out within 24 hours in 70.9% and within 48 h in 93.0%. The time to de-escalation was significantly shorter using POC (25.4 hours) compared to laboratory-based testing (58.9 hours; P < .001). Implementing this strategy led to a reduction of €211,150.50 in medication costs.
Conclusions
CYP2C19 genotype-guided-de-escalation in an all-comers ACS population is feasible. POC genotyping leads to shorter turnaround times and quicker de-escalation. Time to de-escalation from ticagrelor to clopidogrel in noncarriers was short, with high physician adherence to genotype results.
Introduction
Red blood cell distribution width (RDW) and bilirubin have been proved to be prognostic factors for various types of cancer. However, their prognostic value in patients with gastric ...cancer (GC) remains largely unknown.
Methods
To verify whether RDW and bilirubin are prognostic factors for patients with GC, we performed a cross‐sectional study to analyze the relationship between RDW, bilirubin, and the clinical characteristics of patients with GC. Medical records of all newly diagnosed and pathologically proved patients with GC admitted to Changzheng Hospital between January 2016 and July 2016 were retrospectively reviewed. The relationship between RDW, bilirubin, and the clinical characteristics of patients with GC was analyzed.
Results
A total of 144 patients with GC were enrolled. Patients with GC had significantly higher RDW than healthy controls, even after adjusting for hemoglobin, while total bilirubin (TBIL), direct bilirubin (DBIL) and indirect bilirubin (IBIL) were significantly decreased. Furthermore, RDW and bilirubin were significantly correlated with tumor stage, as well as carcinoembryonic antigen (CEA) and carbohydrate antigen 19‐9 (CA19‐9).
Conclusion
Our study indicated that RDW and bilirubin could be potential prognostic factors for patients of GC.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract The Nupix-R1 is a prototype Monolithic Active Pixel Sensor designed for the Electron-ion collider in China. It consists of 128 rows × 128 columns of square pixels with a pitch of 26.3 µm. ...Since it is implemented in a 130 nm commercial triple-well process, the in-pixel circuit contains only NMOS transistors. The Nupix-R1 can simultaneously measure the energy, arrival time and position of particle hits. In addition, it can also record only the hit positions with a novel zero-compression scheme to increase the readout speed and reduce the data volume. This paper will discuss the design of the Nupix-R1 sensor.
Abstract
The Monolithic Active Pixel Sensor (MAPS) is a good candidate for the inner
tracking system of the Electron–Ion Collider in China (EicC). Hence, a
MAPS with a pixel pitch of ∼30 µm is being ...designed. Two
130 nm CMOS processes have been proposed as candidates for this MAPS
design. The first one is a commercial standard twin-well low-resistivity
(<50 Ω cm
−3
) process, and the other
one is a quadruple-well high-resistivity (>1 kΩ cm
−3
)
process. A 3-dimensional TCAD model of the pixels has been established to
evaluate the Minimum Ionizing Particles (MIPs) induced charge collection in
these two processes. This paper will discuss the study of charge collection
efficiency, charge collection time, and charge sharing among pixels.
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