In patients with acute myocardial infarction receiving potent antiplatelet therapy, the bleeding risk remains high during the maintenance phase. We sought data on a uniform unguided de-escalation ...strategy of dual antiplatelet therapy (DAPT) from ticagrelor to clopidogrel after acute myocardial infarction.
In this open-label, assessor-masked, multicentre, non-inferiority, randomised trial (TALOS-AMI), patients at 32 institutes in South Korea with acute myocardial infarction receiving aspirin and ticagrelor without major ischaemic or bleeding events during the first month after index percutaneous coronary intervention (PCI) were randomly assigned in a 1:1 ratio to a de-escalation (clopidogrel plus aspirin) or active control (ticagrelor plus aspirin) group. Unguided de-escalation without a loading dose of clopidogrel was adopted when switching from ticagrelor to clopidogrel. The primary endpoint was a composite of cardiovascular death, myocardial infarction, stroke, or bleeding type 2, 3, or 5 according to Bleeding Academic Research Consortium (BARC) criteria from 1 to 12 months. A non-inferiority test was done to assess the safety and efficacy of de-escalation DAPT compared with standard treatment. The hazard ratio (HR) for de-escalation versus active control group in a stratified Cox proportional hazards model was assessed for non-inferiority by means of an HR margin of 1·34, which equates to an absolute difference of 3·0% in the intention-to-treat population and, if significant, a superiority test was done subsequently. To ensure statistical robustness, additional analyses were also done in the per-protocol population. This trial is registered at ClinicalTrials.gov, NCT02018055.
From Feb 26, 2014, to Dec 31, 2018, from 2901 patients screened, 2697 patients were randomly assigned: 1349 patients to de-escalation and 1348 to active control groups. At 12 months, the primary endpoints occurred in 59 (4·6%) in the de-escalation group and 104 (8·2%) patients in the active control group (pnon-inferiority<0·001; HR 0·55 95% CI 0·40–0·76, psuperiority=0·0001). There was no significant difference in composite of cardiovascular death, myocardial infarction, or stroke between de-escalation (2·1%) and the active control group (3·1%; HR 0·69; 95% CI 0·42–1·14, p=0·15). Composite of BARC 2, 3, or 5 bleeding occurred less frequently in the de-escalation group (3·0% vs 5·6%, HR 0·52; 95% CI 0·35–0·77, p=0·0012).
In stabilised patients with acute myocardial infarction after index PCI, a uniform unguided de-escalation strategy significantly reduced the risk of net clinical events up to 12 months, mainly by reducing the bleeding events.
ChongKunDang Pharm, Medtronic, Abbott, and Boston Scientific.
Optogenetics is a powerful technique that allows target-specific spatiotemporal manipulation of neuronal activity for dissection of neural circuits and therapeutic interventions. Recent advances in ...wireless optogenetics technologies have enabled investigation of brain circuits in more natural conditions by releasing animals from tethered optical fibers. However, current wireless implants, which are largely based on battery-powered or battery-free designs, still limit the full potential of in vivo optogenetics in freely moving animals by requiring intermittent battery replacement or a special, bulky wireless power transfer system for continuous device operation, respectively. To address these limitations, here we present a wirelessly rechargeable, fully implantable, soft optoelectronic system that can be remotely and selectively controlled using a smartphone. Combining advantageous features of both battery-powered and battery-free designs, this device system enables seamless full implantation into animals, reliable ubiquitous operation, and intervention-free wireless charging, all of which are desired for chronic in vivo optogenetics. Successful demonstration of the unique capabilities of this device in freely behaving rats forecasts its broad and practical utilities in various neuroscience research and clinical applications.
The priority of synaptic device researches has been given to prove the device potential for the emulation of synaptic dynamics and not to functionalize further synaptic devices for more complex ...learning. Here, we demonstrate an optic-neural synaptic device by implementing synaptic and optical-sensing functions together on h-BN/WSe
heterostructure. This device mimics the colored and color-mixed pattern recognition capabilities of the human vision system when arranged in an optic-neural network. Our synaptic device demonstrates a close to linear weight update trajectory while providing a large number of stable conduction states with less than 1% variation per state. The device operates with low voltage spikes of 0.3 V and consumes only 66 fJ per spike. This consequently facilitates the demonstration of accurate and energy efficient colored and color-mixed pattern recognition. The work will be an important step toward neural networks that comprise neural sensing and training functions for more complex pattern recognition.
Four-dimensional (4D) printing can add active and responsive functions to three-dimensional (3D) printed objects in response to various external stimuli. Light, among others, has a unique advantage ...of remotely controlling structural changes to obtain predesigned shapes. In this study, we demonstrate multicolor 4D printing of shape-memory polymers (SMPs). Using color-dependent selective light absorption and heating in multicolor SMP composites, we realize remote actuation with light illumination. We experimentally investigate the temperature changes in colored SMPs and observe a clear difference between the different colors. We also present simulations and analytical calculations to theoretically model the structural variations in multicolor composites. Finally, we consider a multicolor hinged structure and demonstrate the multistep actuation by changing the color of light and duration of illumination. 4D printing can allow complex, multicolor geometries with predesigned responses. Moreover, SMPs can be reused multiple times for thermal actuation by simply conducting thermomechanical programming again. Therefore, 4D printing of multicolor SMP composites have unique merits for light-induced structural changes. Our study indicates that multicolor 4D printing of SMPs are promising for various structural changes and remote actuation.
Select persulfate activation processes were demonstrated to initiate oxidation not reliant on sulfate radicals, although the underlying mechanism has yet to be identified. This study explored singlet ...oxygenation and mediated electron transfer as plausible nonradical mechanisms for organic degradation by carbon nanotube (CNT)-activated peroxymonosulfate (PMS). The degradation of furfuryl alcohol (FFA) as a singlet oxygen (1O2) indicator and the kinetic retardation of FFA oxidation in the presence of l-histidine and azide as 1O2 quenchers apparently supported a role of 1O2 in the CNT/PMS system. However, the 1O2 scavenging effect was ascribed to a rapid PMS depletion by l-histidine and azide. A comparison of CNT/PMS and photoexcited Rose Bengal (RB) excluded the possibility of singlet oxygenation during heterogeneous persulfate activation. In contrast to the case of excited RB, solvent exchange (H2O to D2O) did not enhance FFA degradation by CNT/PMS and the pH- and substrate-dependent reactivity of CNT/PMS did not reflect the selective nature of 1O2. Alternatively, concomitant PMS reduction and trichlorophenol oxidation were achieved when PMS and trichlorophenol were physically separated in two chambers using a conductive vertically aligned CNT membrane. This result suggested that CNT-mediated electron transfer from organics to persulfate was primarily responsible for the nonradical degradative route.
Objectives
To evaluate radiomics studies according to radiomics quality score (RQS) and Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis (TRIPOD) to ...provide objective measurement of radiomics research.
Materials and methods
PubMed and Embase were searched for studies published in high clinical imaging journals until December 2018 using the terms “radiomics” and “radiogenomics.” Studies were scored against the items in the RQS and TRIPOD guidelines. Subgroup analyses were performed for journal type (clinical vs. imaging), intended use (diagnostic vs. prognostic), and imaging modality (CT vs. MRI), and articles were compared using Fisher’s exact test and Mann-Whitney analysis.
Results
Seventy-seven articles were included. The mean RQS score was 26.1% of the maximum (9.4 out of 36). The RQS was low in demonstration of clinical utility (19.5%), test-retest analysis (6.5%), prospective study (3.9%), and open science (3.9%). None of the studies conducted a phantom or cost-effectiveness analysis. The adherence rate for TRIPOD was 57.8% (mean) and was particularly low in reporting title (2.6%), stating study objective in abstract and introduction (7.8% and 16.9%), blind assessment of outcome (14.3%), sample size (6.5%), and missing data (11.7%) categories. Studies in clinical journals scored higher and more frequently adopted external validation than imaging journals.
Conclusions
The overall scientific quality and reporting of radiomics studies is insufficient. Scientific improvements need to be made to feature reproducibility, analysis of clinical utility, and open science categories. Reporting of study objectives, blind assessment, sample size, and missing data is deemed to be necessary.
Key Points
• The overall scientific quality and reporting of radiomics studies is insufficient.
• The RQS was low in demonstration of clinical utility, test-retest analysis, prospective study, and open science.
• Room for improvement was shown in TRIPOD in stating study objective in abstract and introduction, blind assessment of outcome, sample size, and missing data categories.
Antiplatelet therapy has shown protective effects against hepatocellular carcinoma (HCC) in preclinical studies. However, it is unclear whether antiplatelet therapy lowers the risk of HCC in patients ...with chronic hepatitis B. A retrospective analysis was conducted of data from 1,674 chronic hepatitis B patients, enrolled between January 2002 and May 2015, whose serum hepatitis B virus DNA levels were suppressed by antivirals to <2,000 IU/mL. The primary and secondary outcomes were development of HCC and bleeding events, respectively. Risk was compared between patients with antiplatelet treatment (aspirin, clopidogrel, or both; antiplatelet group) and patients who were not treated (non‐antiplatelet group) using a time‐varying Cox proportional hazards model for total population and propensity score–matching analysis. The antiplatelet group included 558 patients, and the non‐antiplatelet group had 1,116 patients. During the study period, 63 patients (3.8%) developed HCC. In time‐varying Cox proportional analyses, the antiplatelet group showed a significantly lower risk of HCC (hazard ratio HR, 0.44; 95% confidence interval CI, 0.23–0.85; P = 0.01), regardless of antiplatelet agent. In propensity score–matched pairs, antiplatelet therapy significantly reduced the risk of HCC (HR, 0.34; 95% CI, 0.15‐0.77; P = 0.01). However, the overall risk of bleeding was higher in the antiplatelet group (HR, 3.28; 95% CI, 1.98‐5.42; P < 0.001), particularly for clopidogrel with or without aspirin. Treatment with aspirin alone was not associated with a higher bleeding risk (HR, 1.11; 95% CI, 0.48‐2.54; P = 0.81). Conclusion: Antiplatelet therapy reduces the risk of HCC in chronic hepatitis B patients whose hepatitis B virus is effectively suppressed. However, antiplatelet therapy containing clopidogrel may increase the risk of bleeding. (Hepatology 2017;66:1556–1569)
Objectives
To evaluate the diagnostic performance of attenuation imaging (ATI) in the detection of hepatic steatosis compared with a histopathology gold standard.
Methods
We prospectively enrolled ...108 consecutive patients (35 males; median age, 54.0 years) who underwent percutaneous liver biopsy for evaluation of diffuse liver disease between January 2018 and November 2018 in a tertiary academic center. Grayscale ultrasound examination with ATI was performed just before biopsy, and an attenuation coefficient (AC) was obtained from each patient. The degree of hepatic steatosis, fibrosis stage, and necroinflammatory activity were assessed on histopathologic examination. The significant factor associated with the AC was found by a linear regression analysis, and the diagnostic performance of the AC for the classification into each hepatic steatosis stage was evaluated by receiver operating characteristic (ROC) analysis.
Results
The distribution of hepatic steatosis grade on histopathology was 53/11/22/16/6 for none/mild (< 10%)/mild (≥ 10%)/moderate/severe steatosis, respectively. The area under the ROC curve, sensitivity, specificity, and optimal cutoff AC value for detection of hepatic steatosis ranged from 0.843–0.926, 74.5–100.0%, 77.4–82.8%, and 0.635–0.745, respectively. Multivariate analysis revealed that the degree of steatosis was the only significant determinant factor for the AC.
Conclusions
The AC from ATI provided good diagnostic performance in detecting the varying degrees of hepatic steatosis. The degree of steatosis was the only significant factor affecting the AC, whereas fibrosis and inflammation were not.
Key Points
• Attenuation imaging (ATI) is based on two-dimensional grayscale ultrasound images that can incorporate into routine ultrasound examinations with less than 2 min of acquisition time.
• ATI provided good diagnostic performance in detecting the varying degrees of hepatic steatosis with an area under the ROC curves ranging from 0.843 to 0.926, and there was no technical failure in this study indicating high applicability of this technique.
• The degree of hepatic steatosis was the only significant factor affecting the result of ATI examination.
Despite the integral role of cephalometric analysis in orthodontics, there have been limitations regarding the reliability, accuracy, etc. of cephalometric landmarks tracing. Attempts on developing ...automatic plotting systems have continuously been made but they are insufficient for clinical applications due to low reliability of specific landmarks. In this study, we aimed to develop a novel framework for locating cephalometric landmarks with confidence regions using Bayesian Convolutional Neural Networks (BCNN).
We have trained our model with the dataset from the ISBI 2015 grand challenge in dental X-ray image analysis. The overall algorithm consisted of a region of interest (ROI) extraction of landmarks and landmarks estimation considering uncertainty. Prediction data produced from the Bayesian model has been dealt with post-processing methods with respect to pixel probabilities and uncertainties.
Our framework showed a mean landmark error (LE) of 1.53 ± 1.74 mm and achieved a successful detection rate (SDR) of 82.11, 92.28 and 95.95%, respectively, in the 2, 3, and 4 mm range. Especially, the most erroneous point in preceding studies, Gonion, reduced nearly halves of its error compared to the others. Additionally, our results demonstrated significantly higher performance in identifying anatomical abnormalities. By providing confidence regions (95%) that consider uncertainty, our framework can provide clinical convenience and contribute to making better decisions.
Our framework provides cephalometric landmarks and their confidence regions, which could be used as a computer-aided diagnosis tool and education.
Acute rejection is hazardous to graft survival in kidney transplant recipients (KTRs). We aimed to identify novel biomarkers for early diagnosis of acute T cell-mediated rejection (TCMR) in urinary ...exosomes of KTRs.
Among 458 graft biopsies enrolled in a cross-sectional multicenter study, 22 patients with stable graft function (STA) who had not shown pathologic abnormality and 25 patients who diagnosed biopsy-proven TCMR were analyzed. We performed proteomic analysis using nano-ultra performance liquid chromatography-tandem mass spectrometry (nano-UPLC-MS/MS) to identify candidate biomarkers for early TCMR diagnosis on urinary exosomes. We confirmed the protein levels of each candidate biomarker by western blot analysis.
A total of 169 urinary exosome proteins were identified by nano-UPLC-MS/MS. Forty-six proteins showed increased expression in STA patients, while 17 proteins were increased in TCMR patients. Among them, we selected five proteins as candidate biomarkers for early diagnosis of TCMR according to significance, degree of quantity variance, and information from the ExoCarta database. We confirmed the proteomic expression levels of five candidate biomarkers by western blot analysis in each patient. Of all candidate biomarkers, tetraspanin-1 and hemopexin were significantly higher in TCMR patients (STA:TCMR ratio = 1:1.8, P = 0.009, and 1:3.5, P = 0.046, respectively).
Tetraspanin-1 and hemopexin were detected in KTR urine and could act as potential diagnostic proteins for TCMR.
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