Background Liver cirrhotic patients with nonvalvular atrial fibrillation have been excluded from randomized clinical studies regarding oral anticoagulants for stroke prevention. Whether non-vitamin K ...antagonist oral anticoagulants ( NOAC s) are superior to warfarin for these patients remains unclear. Methods and Results This nationwide retrospective cohort study, with data collected from the Taiwan National Health Insurance Research Database, enrolled 2428 liver cirrhotic patients with nonvalvular atrial fibrillation taking apixaban (n=171), dabigatran (n=535), rivaroxaban (n=732), or warfarin (n=990) from June 1, 2012, to December 31, 2016. We used propensity score-based stabilized weights to balance covariates across study groups. Patients were followed until the occurrence of an event or the end date of study. The NOAC group (n=1438) showed risk of ischemic stroke/systemic embolism and intracranial hemorrhage comparable to that of the warfarin group (n=990) after adjustment. The NOAC group showed significantly lower risk of gastrointestinal bleeding (hazard ratio: 0.51 95% CI, 0.32-0.79; P=0.0030) and all major bleeding (hazard ratio: 0.51 95% CI, 0.32-0.74; P=0.0003) compared with warfarin group. Overall, 90% (n=1290) of patients were taking a low-dose NOAC (apixaban 2.5 mg twice daily, rivaroxaban 10-15 mg daily, or dabigatran 110 mg twice daily). The subgroup analysis indicated that both dabigatran and rivaroxaban showed lower risk of all major bleeding than warfarin. The advantage of lower gastrointestinal and all major bleeding with NOACs over warfarin is contributed by those subgroups with either nonalcoholic or nonadvanced liver cirrhosis. Conclusions NOACs have a risk of thromboembolism comparable to that of warfarin and a lower risk of major bleeding among liver cirrhotic Asian patients with nonvalvular atrial fibrillation. Consequently, thromboprophylaxis with low-dose NOAC s may be considered for such patients.
Abstract
Background
Although a few meta-analyses were conducted to compare the risk of incident atrial fibrillation (AF) between sodium-glucose cotransporter-2 inhibitor (SGLT2i), glucagon-like ...peptide-1 receptor agonists (GLP-1RA), and other anti-hyperglycemic agents using indirect or direct comparison, the above analyses showed conflicting results with each other. We aimed to evaluate the risk of new-onset AF associated with the use of SGLT2i, GLP-1RA, and dipeptidyl peptidase-4 inhibitor (DPP4i) among a large longitudinal cohort of diabetic patients.
Methods
In this nationwide retrospective cohort study based on the Taiwan National Health Insurance Research Database, a total of 344,893, 44,370, and 393,100 consecutive patients with type 2 diabetes without preexisting AF receiving GLP-1RA, SGLT2i, and DPP4i, respectively, were enrolled from May 1, 2016, to December 31, 2019. We used 1:1 propensity score matching (PSM) to balance covariates across paired study groups. Patients were followed from the drug index date until the occurrence of AF, death, discontinuation of the index drug, or the end of the study period (December 31, 2020), whichever occurred first.
Results
After PSM, there were 245,442, 43,682, and 39,190 paired cohorts of SGLT2i-DPP4i, SGLT2i-GLP-1RA, and GLP-1RA-DPP4i, respectively. SGLT2i treatment was associated with lower risk of new-onset AF in participants with type 2 diabetes compared with either DPP4i hazard ratio (HR):0.90; 95% confidential interval (CI) 0.84–0.96;
P
= 0.0028 or GLP-1RA HR 0.74; 95% CI 0.63–0.88;
P
= 0.0007 treatment after PSM. There was no difference in the risk of incident AF between GLP-1RA and DPP4i users HR 1.01; 95% CI 0.86–1.19;
P
= 0.8980. The above findings persisted among several important subgroups. Dapagliflozin was specifically associated with a lower risk of new-onset AF compared with DPP4i (
P
interaction = 0.02).
Conclusions
Compared with DPP4i, SGLT2i but not GLP-1RA was associated with a lower risk of incident AF in patients with type 2 diabetes.
The Hippo pathway is a conserved signaling pathway originally defined in
two decades ago. Deregulation of the Hippo pathway leads to significant overgrowth in phenotypes and ultimately initiation of ...tumorigenesis in various tissues. The major WW domain proteins in the Hippo pathway are YAP and TAZ, which regulate embryonic development, organ growth, tissue regeneration, stem cell pluripotency, and tumorigenesis. Recent reports reveal the novel roles of YAP/TAZ in establishing the precise balance of stem cell niches, promoting the production of induced pluripotent stem cells (iPSCs), and provoking signals for regeneration and cancer initiation. Activation of YAP/TAZ, for example, results in the expansion of progenitor cells, which promotes regeneration after tissue damage. YAP is highly expressed in self-renewing pluripotent stem cells. Overexpression of YAP halts stem cell differentiation and yet maintains the inherent stem cell properties. A success in reprograming iPSCs by the transfection of cells with Oct3/4, Sox2, and Yap expression constructs has recently been shown. In this review, we update the current knowledge and the latest progress in the WW domain proteins of the Hippo pathway in relevance to stem cell biology, and provide a thorough understanding in the tissue homeostasis and identification of potential targets to block tumor development. We also provide the regulatory role of tumor suppressor WWOX in the upstream of TGF-β, Hyal-2, and Wnt signaling that cross talks with the Hippo pathway.
Background The ROCKET AF (Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation) evaluated ...rivaroxaban (20/15 mg/d) versus warfarin in patients with atrial fibrillation. A separate trial, J-ROCKET AF (Japanese ROCKET AF), compared rivaroxaban (15/10 mg/d) and warfarin in Japanese patients with atrial fibrillation. Data about rivaroxaban following J-ROCKET AF criteria compared with warfarin and ROCKET AF dosage were limited. Methods and Results This retrospective study used medical data from a multicenter healthcare provider in Taiwan that included 3162 patients taking rivaroxaban. Among 2320 patients with an estimated glomerular filtration rate (eGFR) ≥50 mL/min per 1.73 m
, 384 and 1936 patients followed the ROCKET AF (20 mg/d) and J-ROCKET AF (15 mg/d) recommendation, respectively. Among 842 patients with an eGFR <50 mL/min per 1.73 m
, 422 and 420 patients followed the ROCKET AF (15 mg/d) and J-ROCKET AF (10 mg/d) recommendation, respectively. A total of 2053 patients with atrial fibrillation receiving warfarin were identified. Rivaroxaban following either ROCKET AF or J-ROCKET AF dosage criteria was associated with a comparable risk of thromboembolism but a lower risk of bleeding than warfarin. For patients with an eGFR ≥50 mL/min per 1.73 m
, risks of clinical events did not differ significantly between the 2 dosage criteria of rivaroxaban. For patients with an eGFR <50 mL/min per 1.73 m
, the ROCKET AF dosage was associated with a higher risk of major bleeding compared with the J-ROCKET AF dosage (hazard ratio, 2.70;
=0.0445) without significant differences regarding the risk of ischemic events. Conclusions In Asian patients with atrial fibrillation, the J-ROCKET AF dosage was as effective as the ROCKET AF dosage irrespective of renal function. The risk of major bleeding was lower with the J-ROCKET AF dosage in patients with an eGFR <50 mL/min per 1.73 m
. Compared with warfarin, rivaroxaban following either dosage criteria was effective and even safer.
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.
Background Transcatheter aortic valve-in-valve (VIV) procedure is a safe alternative to conventional reoperation for bioprosthetic dysfunction. Balloon-expandable valve (BEV) and self-expanding valve ...(SEV) are the 2 major types of devices used. Evidence regarding the comparison of the 2 valves remains scarce. Methods A systematic review and meta-analysis was conducted to compare the outcomes of BEV and SEV in transcatheter VIV for aortic bioprostheses dysfunction. A computerized search of Medline, PubMed, Embase, and Cochrane databases was performed. English-language journal articles reporting SEV or BEV outcomes of at least 10 patients were included. Results In total, 27 studies were included, with 2,269 and 1,671 patients in the BEV and SEV groups, respectively. Rates of 30-day mortality and stroke did not differ significantly between the 2 groups. However, BEV was associated with significantly lower rates of postprocedural permanent pacemaker implantation (3.8% vs. 12%; P 0.001). Regarding echocardiographic parameters, SEV was associated with larger postprocedural effective orifice area at 30 days (1.53 cm.sup.2 vs. 1.23 cm.sup.2 ; P 0.001) and 1 year (1.55 cm.sup.2 vs. 1.22 cm.sup.2 ; P 0.001). Conclusions For patients who underwent transcatheter aortic VIV, SEV was associated with larger postprocedural effective orifice area but higher rates of permanent pacemaker implantation. These findings provide valuable information for optimizing device selection for transcatheter aortic VIV.
Viologen (V) based molecules are classic and prestigious electrochromic (EC) materials which have dramatic optical contrast and tunable coloring states in solution-type electrochromic devices (ECDs). ...However, the stability of viologen based ECDs was significantly reduced by the dimer formation, and the resultant aggregation of viologens, which may occur once viologen dication (V2+) was reduced to viologen radical cation (V+•). To diminish this phenomenon, two novel symmetric benzyl-based viologens including 1,1′-bis(3,5-bis(trifluoromethyl)-benzyl)-4,4′-bipyridine-1,1′-diium (DTFMBzV) and 1,1′-bis(4-(trifluoromethyl)benzyl)-4,4′-bipyridine-1,1′-diium (TFMBzV) with various numbers of trifluoromethyl (CF3) substituents were synthesized and studied in this work. Substituent of CF3 in benzyl-based viologens not only enhance its optical property by increasing the π‒conjugation of bipyridine, but also avoid the aggregation by repulsing the viologen with fluorine atoms. The electrochromic performance of ECDs consisted of benzyl viologen (BzV/Fc ECD) and benzyl-based viologens with various numbers of CF3 substituents (DTFMBzV/Fc ECD and TFMBzV/Fc ECD) incorporated with ferrocene (Fc) were studied. According to the result of UV–vis absorbance spectra, the absorbances of benzyl viologen-based ECDs were strengthened at 399 and 605 nm by increasing the number of CF3 substituents. The DTFMBzV/Fc ECD gives a high transmittance change (ΔT) of 63.5% at 605 nm initially with a short response time (<3 s) by biasing the cell potential from 0 to 1.1 V. As for the stability, the DTFMBzV/Fc ECD exhibits an extremely high retention (97% of its initial ΔT) after switching for 10,000 cycles, which implied the dimerization of viologen was diminished by introducing the CF3 substituents with stronger electrostatic repulsion. As the result, DTFMBzV/Fc ECD exhibited the best electrochromic performance in terms of optical contrast and long-term stability. This study provides a simple yet effective strategy to tailing the electrochromic properties of viologen molecules for further application in electrochromism.
Display omitted
•Stable benzyl viologens were synthesized with trifluoromethyl (CF3) substituents.•The effect of CF3 groups enhances the optical property and improves the stability.•The TFMBzV/Fc ECD shows the initial transmittance change (ΔT) of 60.3% at 605 nm.•The DTFMBzV/Fc ECD reveals the initial ΔT of 63.5% at 605 nm.•The DTFMBzV/Fc ECD retains 97% of its initial ΔT up to 10,000 switching cycles.
Studies specifically examining the association between glycated hemoglobin A1c (HbA1c) levels and ischemic stroke/systemic thromboembolism (IS/SE) risk in atrial fibrillation (AF) patients are ...limited. Here, we investigated the association between HbA1c levels and the risk of IS/SE, as well as major bleeding, among AF patients with or without oral anticoagulants (OACs). We also compared the effectiveness and safety of warfarin and direct oral anticoagulants (DOACs) in different HbA1c categories.
We utilized medical data from a multi-center healthcare provider in Taiwan, which included 34,036 AF patients with serum HbA1c data available within 3 months after AF being diagnosed. Patients were divided into seven study groups according to their HbA1c levels: < 5.4%, 5.4%-5.6%, 5.7%-5.9%, 6.0%-6.4%, 6.5%-6.9%, 7.0%-7.9%, and ≥ 8.0%. The risks of IS/SE and major bleeding were compared among the groups after adjusting for baseline stroke and bleeding risk factors.
Compared with the patients with HbA1c level < 5.4%, IS/SE risk significantly increased at HbA1c levels higher than 6.5% adjusted hazard ratio (HR): 1.20, 95% confidence interval (CI): 1.00-1.43 for HbA1c level 6.5%-6.9%; 1.32, (95% CI 1.11-1.57) for HbA1c level 7.0%-7.9%; and 1.48 (95% CI 1.25-1.76) for HbA1c level ≥ 8.0%. These results were generally consistent in AF patients without OACs (n = 24,931). However, among 9105 patients receiving OACs, IS/SE risk was not higher for patients having higher HbA1c levels. The risk of major bleeding was comparable across all HbA1c categories. Compared with warfarin, DOACs were associated with lower risks of IS/SE (adjusted HR: 0.61, 95% CI 0.49-0.75) and major bleeding (adjusted HR: 0.30, 95% CI 0.21-0.42) without interactions across different HbA1c categories (all P interactions > 0.05).
For AF patients, IS/SE risk significantly increased once HbA1c levels exceeded 6.5%, and OACs may attenuate these associations. Compared with warfarin, DOACs were more effective and safer across broad HbA1c categories. Therefore, in addition to prescribing DOACs when indicated, more aggressive glycemic control to achieve an HbA1c level < 6.5% may be considered for eligible AF patients and should be tested in further prospective studies.
Aims
To compare the surgical outcomes of conventional surgeries with or without concomitant transobturator vaginal mesh (TVM) for ≥Stage 3 pelvic organ prolapse (POP).
Methods
We retrospectively ...investigated 166 women who received conventional surgery including vaginal total hysterectomy, modified McCall culdoplasty, and AP‐repair (conventional group) and 98 women with concomitant TVM (mesh group). Follow‐up at 3, 12, and 24 months comprised symptom interview, pelvic examination, and ultrasound assessments. The primary outcome was anatomical success defined as ≤Stage 1 POP. Secondary outcomes were subjective symptoms, ultrasound manifestations, and complications.
Results
Both groups showed improvements in functional and anatomical outcomes after operations. Compared with the conventional group, the mesh group had higher rates of de novo stress urinary incontinence (SUI) at 3‐month (3.6% vs 19.4%; P < .001), 12‐month (3.7% vs 26.4%; P < .001), and 24‐month (2.4% vs 21.4%; P = .001) follow‐up, a higher POP‐C point (−7.3 ± 0.7 cm vs −7.6 ± 0.6 cm; P < .001) at 3‐month follow‐up, a smaller straining bladder neck angle indicating a more cranioventral straining bladder neck position (117 ± 25° vs 102 ± 20°; P < .001) at 3‐month follow‐up, and a less bladder neck mobility at 3‐month (19 ± 24° vs 8 ± 14°; P = .002) and 12‐month (26 ± 18° vs 12 ± 15°; P = .003) follow‐up.
Conclusions
Concomitant TVM is associated with a higher rate of de novo SUI, more cranioventral straining bladder neck position, and less bladder neck mobility.
PDF
