Stroke prevention is the cornerstone of management of atrial fibrillation (AF), and non-vitamin K antagonist oral anticoagulants (NOACs) are commonly prescribed. Because routine monitoring of ...anticoagulant effects of NOACs is not necessary, appropriate dosing following the criteria of each NOACs defined in pivotal randomized trials is important. Real-world data demonstrate that underdosing NOACs is associated with a higher risk of ischemic stroke without a lower risk of major bleeding. Furthermore, renal function of AF patients should be assessed using the Cockcroft-Gault formula to prevent overestimation that could result in overdosing of NOACs. The assessment of bleeding risk is important, and the HAS-BLED score should be used to help identify patients at high risk of bleeding (HAS-BLED score ≥3). Moreover, the HAS-BLED score should be reassessed at periodic intervals to address potentially modifiable bleeding risk factors because bleeding risks of AF patients are not static. When managing NOAC-related bleeding episodes, the possibility of occult malignancies (e.g., grastrointestinal GI tract cancers for patients experiencing GI bleeding and bladder cancer for patients with hematuria) should be kept in mind. Addressing all of these issues is crucial to achieving better clinical outcomes for anticoagulated AF patients. More efforts are necessary to incorporate clear and easy-to-follow recommendations about optimal management of anticoagulation into the guidelines to improve AF patient care.
Whether sodium glucose co-transporter 2 inhibitors (SGLT2i) are associated with a lower risk of cardiovascular as well as adverse lower limb events in patients with type-2 diabetes mellitus (T2DM) ...and concomitant peripheral artery disease (PAD) is unclear. We aimed to evaluate the risk of cardiovascular and limb events, and death associated with the use of SGLT2i compared with dipeptidyl peptidase-4 inhibitors (DPP4i) among a longitudinal and national cohort of patients with T2DM.
In this nationwide retrospective cohort study based on the Taiwan National Health Insurance Research Database, we identified a total of 11,431 and 93,972 consecutive T2DM patients with PAD taking SGLT2i and DPP4i, respectively, from May 1, 2016, to December 31, 2017. We used 1:1 propensity score matching (PSM) to balance covariates across study groups. Patients were followed from the drug index date until the occurrence of clinical outcomes, death, discontinuation of the index drug, or the end of the study period, whichever occurred first.
Overall, 56% and 44% of the patients were treated with dapagliflozin and empagliflozin, respectively. The use of SGLT2i had comparable risks of ischemic stroke and acute myocardial infarction, and was associated with lower risks of congestive heart failure (CHF) hazard ratio (HR): 0.66; 95% confidence interval (CI) 0.49-0.89; p = 0.0062, lower limb ischemia requiring revascularization (HR: 0.73; 95% CI 0.54-0.98; p = 0.0367) or amputation (HR: 0.43; 95% CI 0.30-0.62; p < 0.0001), and cardiovascular death (HR: 0.67; 95% CI 0.49-0.90; p = 0.0089) when compared with the DDP4i group after PSM. The subgroup analysis revealed consistent results for CHF and major adverse limb outcomes for SGLT2i versus DPP4i among patients aged ≥ 75 years, the presence of chronic kidney disease and established cardiovascular disease was consistent with the main analysis.
SGLT2i were associated with lower risks of CHF and adverse lower limb events compared with DPP4i among patients with T2DM and PAD in real-world practice.
Objective
To evaluate the accuracy of MeMoSA®, a mobile phone application to review images of oral lesions in identifying oral cancers and oral potentially malignant disorders requiring referral.
...Subjects and Methods
A prospective study of 355 participants, including 280 with oral lesions/variants was conducted. Adults aged ≥18 treated at tertiary referral centres were included. Images of the oral cavity were taken using MeMoSA®. The identification of the presence of lesion/variant and referral decision made using MeMoSA® were compared to clinical oral examination, using kappa statistics for intra‐rater agreement. Sensitivity, specificity, concordance and F1 score were computed. Images were reviewed by an off‐site specialist and inter‐rater agreement was evaluated. Images from sequential clinical visits were compared to evaluate observable changes in the lesions.
Results
Kappa values comparing MeMoSA® with clinical oral examination in detecting a lesion and referral decision was 0.604 and 0.892, respectively. Sensitivity and specificity for referral decision were 94.0% and 95.5%. Concordance and F1 score were 94.9% and 93.3%, respectively. Inter‐rater agreement for a referral decision was 0.825. Progression or regression of lesions were systematically documented using MeMoSA®.
Conclusion
Referral decisions made through MeMoSA® is highly comparable to clinical examination demonstrating it is a reliable telemedicine tool to facilitate the identification of high‐risk lesions for early management.
Hyperglycemia, which can lead to apoptosis, hypertrophy, fibrosis, and induces hyperinflammation in diabetic vascular complications due to oxidative stress. In order to elucidate the potential dual ...roles and regulatory signal transduction of TGF-β1 and TGF-β2 in human trabecular meshwork cells (HTMCs), we established an oxidative cell model in HTMCs using 5.5, 25, 50, and 100 mM d-glucose-supplemented media and characterized the TGF-β-related oxidative stress pathway.
Further analysis was conducted to investigate oxidative damage and protein alterations in the HTMC caused by the signal transduction. This was done through a series of qualitative cell function studies, such as cell viability/apoptosis analysis, intracellular reactive oxygen species (ROS) detection, analysis of calcium release concentration, immunoblot analysis to detect the related protein expression alteration, and analysis of cell fibrosis to study the effect of different severities of hyperglycemia. Also, we illustrated the role of TGF-β1/2 in oxidative stress-induced injury by shRNA-mediated knockdown or stimulation with recombinant human TGF-β1 protein (rhTGF-β1).
Results from the protein expression analysis showed that p-JNK, p-p38, p-AKT, and related SMAD family members were upregulated in HTMCs under hyperglycemia. In the cell functional assays, HTMCs treated with rhTGFβ-1 (1 ng/mL) under hyperglycemic conditions showed higher proliferation rates and lower ROS and calcium levels.
To summarize, mechanistic analyses in HTMCs showed that hyperglycemia-induced oxidative stress activated TGF-β1 along with its associated pathway.
While at low concentrations, TGF-β1 protects cells from antioxidation, whereas at high concentrations, it accumulates in the extracellular matrix, causing further HTMC dysfunction.
Objective
To describe the development of a platform for image collection and annotation that resulted in a multi‐sourced international image dataset of oral lesions to facilitate the development of ...automated lesion classification algorithms.
Materials and Methods
We developed a web‐interface, hosted on a web server to collect oral lesions images from international partners. Further, we developed a customised annotation tool, also a web‐interface for systematic annotation of images to build a rich clinically labelled dataset. We evaluated the sensitivities comparing referral decisions through the annotation process with the clinical diagnosis of the lesions.
Results
The image repository hosts 2474 images of oral lesions consisting of oral cancer, oral potentially malignant disorders and other oral lesions that were collected through MeMoSA® UPLOAD. Eight‐hundred images were annotated by seven oral medicine specialists on MeMoSA®ANNOTATE, to mark the lesion and to collect clinical labels. The sensitivity in referral decision for all lesions that required a referral for cancer management/surveillance was moderate to high depending on the type of lesion (64.3%–100%).
Conclusion
This is the first description of a database with clinically labelled oral lesions. This database could accelerate the improvement of AI algorithms that can promote the early detection of high‐risk oral lesions.
Abstract
Aims
Left ventricular (LV) ejection fraction (EF) and global longitudinal strain (GLS) help identify heart failure (HF) patients who are at risk for adverse outcomes. This study aimed to ...determine whether global myocardial work (GMW), derived from non-invasive LV pressure-strain loops, can provide incremental prognostic information over EF and GLS in patients with HF and reduced EF (HFrEF).
Methods and results
We retrospectively analysed 508 patients (age 62.9 ± 15.8 years, 29.1% female) with LVEF ≤40%. The study endpoint was a composite of all-cause death and HF hospitalization. The incremental value of GMW over clinical and echocardiographic variables including EF and GLS for the association with the composite endpoint was assessed using Cox regression analyses. Over a 1-year follow-up, 183 patients reached the endpoint. Baseline variables associated with the endpoint were age, haemoglobin, LV end-systolic volume, New York Heart Association Class III or IV, E/e′ ratio, pulmonary artery systolic pressure, EF, and GLS. Cox regression analysis revealed that GMW hazard ratio (HR) 1.15, 95% confidence interval (CI) 1.05–1.25, per 100-mmHg% decrease added incremental prognostic value over these variables. Both EF and GLS were not independent variables when GMW was included in the model. Patients with GMW <750 mmHg% were associated with a significantly higher risk of all-cause death and HF hospitalization (HR 3.33, 95% CI 2.31–4.80) than patients with GMW ≥750 mmHg%.
Conclusion
In patients with HFrEF, GMW provides incremental prognostic information over EF and GLS regarding risk of all-cause death and HF hospitalization.
ABSTRACT
Nonhealing wounds with various forms of complications have been a major challenge for patients with different diseases, and few data are available regarding the clinical significance of ...platelet‐derived growth factor‐AA (PDGF‐AA) in the enhanced wound healing with stem cells, and the precise molecular mechanism remains unclear. The study aims to investigate the role of PDGF‐AA in adipose‐derived stem cells (ASCs) and endothelial progenitor cells (EPCs) enhancing wound healing. In this study, ASCs and EPCs were applied to treat wounds in an animal wound model with a wound‐healing assay. We knocked down PDGF‐AA expression in ASCs using the PDGF‐AA short hairpin RNA technique and investigated the related molecular mechanism. The wound model and wound‐healing assay of the study showed that transplantation of ASCs could enhance wound healing. The results showed that the PDGF‐AA knockdown ASC group had much less improvement of wound healing than other groups treated with wild‐type ASCs in wound tissues. The regulation of PDGF‐AA in ASCs may contribute to improve wound healing through the PI3K7Akt/eNOS signaling pathway. The data indicated that PDGF‐AA might play a vital role in ASCs and EPCs enhancing wound healing, possibly by its effects on angiogenesis. It would be a potential approach using PDGF‐AA for clinical treatment of chronic wounds.—Wu, L.‐W., Chen, W.‐L., Huang, S.‐M., Chan, J. Y.‐H. Platelet‐derived growth factor AA is a substantial factor in the ability of adipose‐derived stem cells and endothelial progenitor cells to enhance wound healing. FASEB J. 33, 2388–2395 (2019). www.fasebj.org
Whether dabigatran is associated with different risks of cardiovascular, bleeding events, and mortality from warfarin in Asian patients with nonvalvular atrial fibrillation remains unclear.
We used ...the Taiwan National Health Insurance Research Database to obtain 9940 and 9913 nonvalvular atrial fibrillation patients taking dabigatran and warfarin, respectively, from June 1, 2012, to December 31, 2013, as the dynamic cohort. Inverse probability of treatment weighting using propensity scores was used to balance covariates across 2 study groups. Patients were followed up until the first occurrence of any study outcome or end date of study.
During a median follow-up period of 0.67 years, there were 526 outcomes for dabigatran group. The hazard ratios (95% confidence intervals) comparing dabigatran with warfarin (reference) were as follows: ischemic stroke, 0.62 (0.52-0.73; P<0.0001); myocardial infarction, 0.67 (0.43-1.05; P=0.0803); intracranial hemorrhage, 0.44 (0.32-0.60; P<0.0001); major gastrointestinal bleeding, 0.99 (0.66-1.49; P=0.9658); all hospitalized major bleeding, 0.58 (0.46-0.74; P<0.0001); and all-cause mortality, 0.45 (0.38-0.53; P<0.0001). Dabigatran did not increase the risk of myocardial infarction or major gastrointestinal bleeding in all age groups when compared with warfarin. Total 8772 patients (88%) took a 110-mg dose in dabigatran group. The magnitude of effect for each outcome of 110-mg was comparable with that of 150-mg dose in the subgroup analysis.
In real-world practice, dabigatran was associated with a reduced risk of ischemic stroke, intracranial hemorrhage, all hospitalized major bleeding, and all-cause mortality compared with warfarin in Asian patients with nonvalvular atrial fibrillation. Dabigatran did not increase the risk of major gastrointestinal bleeding or myocardial infarction compared with warfarin.
The present study examined the associations between cyberbullying involvement and sociodemographic characteristics, autistic social impairment and attention-deficit/hyperactivity disorder and ...oppositional defiant disorder (ODD) symptoms in 219 adolescents with high-functioning autism spectrum disorder (ASD). Moreover, the associations between cyberbullying involvement and depression, anxiety, and suicidality were also examined. Adolescents self-reported higher rates of being a victim or perpetrator of cyberbullying than were reported by their parents. Increased age and had more severe ODD symptoms were significantly associated with being victims or perpetrators of cyberbullying. Being a victim but not a perpetrator of cyberbullying was significantly associated with depression, anxiety, and suicidality. Cyberbullying victimization and perpetration should be routinely surveyed in adolescents with high-functioning ASD.
The introduction of non-vitamin K antagonist oral anticoagulants (NOACs), with a non-inferior or superior clinical efficacy profile compared to vitamin K antagonists (VKAs), has significantly ...improved the safety profile and treatment adherence of patients with non-valvular atrial fibrillation (AF). However, few studies have compared the effectiveness and safety of NOACs. Therefore, we conducted this systematic review and network meta-analysis to compare the safety and clinical effectiveness of NOACs and VKAs in patients with non-valvular AF.
An online bibliographic search was conducted to retrieve real-world evidence studies published between January 2019 and June 2022.
Dabigatran was associated with lower risks of major bleeding, ischemic stroke, and intracranial hemorrhage than warfarin. Among the NOACs, only dabigatran had a lower risk of all-cause mortality than warfarin. Dabigatran was also associated with lower risks of major bleeding and intracranial hemorrhage than rivaroxaban.
Our meta-analysis confirms that dabigatran's real-world safety and clinical effectiveness align with the results of pivotal clinical trials.
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