152 research outputs found
The antimicrobial activity of magnetron sputtered Ag doped aluminum oxide coatings in vitro
The effect of Ag-doped aluminium oxide coatings deposited by magnetron sputtering method on the antibacterial efficiency against Gram-positive, Gram-negative bacteria and fungi has been investigated. The structure and composition of coatings were analysed by means of scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDS), photoelectron spectroscopy (XPS) methods. The results of the study suggest that Ag-doped aluminium oxide coatings demonstrate improved bactericidal effect and have great potential in various medical applications.ΠΠΎΡΠ»ΡΠ΄ΠΆΠ΅Π½ΠΎ Π²ΠΏΠ»ΠΈΠ² ΠΏΠΎΠΊΡΠΈΡΡΡΠ² ΠΎΠΊΡΠΈΠ΄Ρ Π°Π»ΡΠΌΡΠ½ΡΡ Π·Ρ ΡΡΡΠ±Π»ΠΎΠΌ, Π½Π°Π½Π΅ΡΠ΅Π½ΠΈΡ
ΠΌΠ΅ΡΠΎΠ΄ΠΎΠΌ ΠΌΠ°Π³Π½Π΅ΡΡΠΎΠ½Π½ΠΎΠ³ΠΎ Π½Π°ΠΏΠΈΠ»Π΅Π½Π½Ρ Π½Π° Π°Π½ΡΠΈΠ±Π°ΠΊΡΠ΅ΡΡΠ°Π»ΡΠ½Ρ Π΅ΡΠ΅ΠΊΡΠΈΠ²Π½ΡΡΡΡ ΠΏΡΠΎΡΠΈ Π³ΡΠ°ΠΌΠΏΠΎΠ·ΠΈΡΠΈΠ²Π½ΠΈΡ
, Π³ΡΠ°ΠΌΠ½Π΅Π³Π°ΡΠΈΠ²Π½ΠΈΡ
Π±Π°ΠΊΡΠ΅ΡΡΠΉ ΡΠ° Π³ΡΠΈΠ±ΠΊΡΠ². Π‘ΡΡΡΠΊΡΡΡΠ° ΡΠ° ΡΠΊΠ»Π°Π΄ ΠΏΠΎΠΊΡΠΈΡΡΡΠ² Π±ΡΠ»ΠΈ ΠΏΡΠΎΠ°Π½Π°Π»ΡΠ·ΠΎΠ²Π°Π½Ρ Π·Π° Π΄ΠΎΠΏΠΎΠΌΠΎΠ³ΠΎΡ ΡΠΊΠ°Π½ΡΡΡΠΎΡ Π΅Π»Π΅ΠΊΡΡΠΎΠ½Π½ΠΎΡ ΠΌΡΠΊΡΠΎΡΠΊΠΎΠΏΡΡ (SEM), Π΅Π½Π΅ΡΠ³ΠΎΠ΄ΠΈΡΠΏΠ΅ΡΡΡΠΉΠ½ΠΎΡ ΡΠ΅Π½ΡΠ³Π΅Π½ΡΠ²ΡΡΠΊΠΎΡ ΡΠΏΠ΅ΠΊΡΡΠΎΡΠΊΠΎΠΏΡΡ (EDS), ΠΌΠ΅ΡΠΎΠ΄ΡΠ² ΡΠΎΡΠΎΠ΅Π»Π΅ΠΊΡΡΠΎΠ½Π½ΠΎΡ ΡΠΏΠ΅ΠΊΡΡΠΎΡΠΊΠΎΠΏΡΡ (XPS). Π Π΅Π·ΡΠ»ΡΡΠ°ΡΠΈ Π΄ΠΎΡΠ»ΡΠ΄ΠΆΠ΅Π½Π½Ρ Π΄ΠΎΠ·Π²ΠΎΠ»ΡΡΡΡ ΡΡΠ²Π΅ΡΠ΄ΠΆΡΠ²Π°ΡΠΈ, ΡΠΎ ΠΏΠΎΠΊΡΠΈΡΡΡ ΠΎΠΊΡΠΈΠ΄Ρ Π°Π»ΡΠΌΡΠ½ΡΡ Π·Ρ ΡΡΡΠ±Π»ΠΎΠΌ Π΄Π΅ΠΌΠΎΠ½ΡΡΡΡΡΡΡ ΠΏΠΎΠ»ΡΠΏΡΠ΅Π½ΠΈΠΉ Π±Π°ΠΊΡΠ΅ΡΠΈΡΠΈΠ΄Π½ΠΈΠΉ Π΅ΡΠ΅ΠΊΡ Ρ ΠΌΠ°ΡΡΡ Π²Π΅Π»ΠΈΠΊΠΈΠΉ ΠΏΠΎΡΠ΅Π½ΡΡΠ°Π» Π²ΠΈΠΊΠΎΡΠΈΡΡΠ°Π½Π½Ρ Π² ΡΡΠ·Π½ΠΈΡ
Π³Π°Π»ΡΠ·ΡΡ
ΠΌΠ΅Π΄ΠΈΡΠΈΠ½ΠΈ.ΠΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΎ Π²Π»ΠΈΡΠ½ΠΈΠ΅ ΠΏΠΎΠΊΡΡΡΠΈΠΉ ΠΎΠΊΡΠΈΠ΄Π° Π°Π»ΡΠΌΠΈΠ½ΠΈΡ Ρ ΡΠ΅ΡΠ΅Π±ΡΠΎΠΌ, Π½Π°Π½Π΅ΡΠ΅Π½Π½ΡΡ
ΠΌΠ΅ΡΠΎΠ΄ΠΎΠΌ ΠΌΠ°Π³Π½Π΅ΡΡΠΎΠ½Π½ΠΎΠ³ΠΎ Π½Π°ΠΏΡΠ»Π΅Π½ΠΈΡ Π½Π° Π°Π½ΡΠΈΠ±Π°ΠΊΡΠ΅ΡΠΈΠ°Π»ΡΠ½ΡΡ ΡΡΡΠ΅ΠΊΡΠΈΠ²Π½ΠΎΡΡΡ ΠΏΡΠΎΡΠΈΠ² Π³ΡΠ°ΠΌΠΏΠΎΠ»ΠΎΠΆΠΈΡΠ΅Π»ΡΠ½ΡΡ
, Π³ΡΠ°ΠΌΠΎΡΡΠΈΡΠ°ΡΠ΅Π»ΡΠ½ΡΡ
Π±Π°ΠΊΡΠ΅ΡΠΈΠΉ ΠΈ Π³ΡΠΈΠ±ΠΊΠΎΠ². Π‘ΡΡΡΠΊΡΡΡΠ° ΠΈ ΡΠΎΡΡΠ°Π² ΠΏΠΎΠΊΡΡΡΠΈΠΉ Π±ΡΠ»ΠΈ ΠΏΡΠΎΠ°Π½Π°Π»ΠΈΠ·ΠΈΡΠΎΠ²Π°Π½Ρ Ρ ΠΏΠΎΠΌΠΎΡΡΡ ΡΠΊΠ°Π½ΠΈΡΡΡΡΠ΅ΠΉ ΡΠ»Π΅ΠΊΡΡΠΎΠ½Π½ΠΎΠΉ ΠΌΠΈΠΊΡΠΎΡΠΊΠΎΠΏΠΈΠΈ (SEM), ΡΠ½Π΅ΡΠ³ΠΎΠ΄ΠΈΡΠΏΠ΅ΡΡΠΈΠΎΠ½Π½ΠΎΠΉ ΡΠ΅Π½ΡΠ³Π΅Π½ΠΎΠ²ΡΠΊΠΎΠΉ ΡΠΏΠ΅ΠΊΡΡΠΎΡΠΊΠΎΠΏΠΈΠΈ (EDS), ΠΌΠ΅ΡΠΎΠ΄ΠΎΠ² ΡΠΎΡΠΎΡΠ»Π΅ΠΊΡΡΠΎΠ½Π½ΠΎΠΉ ΡΠΏΠ΅ΠΊΡΡΠΎΡΠΊΠΎΠΏΠΈΠΈ (XPS). Π Π΅Π·ΡΠ»ΡΡΠ°ΡΡ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΡ ΠΏΠΎΠ·Π²ΠΎΠ»ΡΡΡ ΡΡΠ²Π΅ΡΠΆΠ΄Π°ΡΡ, ΡΡΠΎ ΠΏΠΎΠΊΡΡΡΠΈΡ ΠΎΠΊΡΠΈΠ΄Π° Π°Π»ΡΠΌΠΈΠ½ΠΈΡ Ρ ΡΠ΅ΡΠ΅Π±ΡΠΎΠΌ Π΄Π΅ΠΌΠΎΠ½ΡΡΡΠΈΡΡΡΡ ΡΠ»ΡΡΡΠ΅Π½Π½ΡΠΉ Π±Π°ΠΊΡΠ΅ΡΠΈΡΠΈΠ΄Π½ΡΠΉ ΡΡΡΠ΅ΠΊΡ ΠΈ ΠΈΠΌΠ΅ΡΡ Π±ΠΎΠ»ΡΡΠΎΠΉ ΠΏΠΎΡΠ΅Π½ΡΠΈΠ°Π» ΠΏΡΠΈΠΌΠ΅Π½Π΅Π½ΠΈΡ Π² ΡΠ°Π·Π»ΠΈΡΠ½ΡΡ
ΠΎΠ±Π»Π°ΡΡΡΡ
ΠΌΠ΅Π΄ΠΈΡΠΈΠ½Ρ
Improvement of microstructure and mechanical properties of high dense SiC ceramics manufactured by high-speed hot pressing
Non-oxide ceramics possess high physical-mechanical properties, corrosion and radiation resistance, which can be used as a protective materials for radioactive wastes disposal. The aim of the present study was the manufacturing of high density SiC ceramics with advanced physical and mechanical parameters. The high performance on the properties of produced ceramics was determined by the dense and monolithic structure. The densified silicon carbide samples possessed good mechanical strength, with a high Vickers micro hardness up to 28.5 GPa.ΠΠ΅Π·ΠΊΠΈΡΠ½Π΅Π²Ρ ΠΊΠ΅ΡΠ°ΠΌΡΡΠ½Ρ ΠΌΠ°ΡΠ΅ΡΡΠ°Π»ΠΈ Π΄Π΅ΠΌΠΎΠ½ΡΡΡΡΡΡΡ Π²ΠΈΡΠΎΠΊΡ ΡΡΠ·ΠΈΠΊΠΎ-ΠΌΠ΅Ρ
Π°Π½ΡΡΠ½Ρ Π²Π»Π°ΡΡΠΈΠ²ΠΎΡΡΡ, ΠΊΠΎΡΠΎΠ·ΡΠΉΠ½Ρ ΡΠ° ΡΠ°Π΄ΡΠ°ΡΡΠΉΠ½Ρ ΡΡΡΠΉΠΊΡΡΡΡ, ΡΠΎ ΡΠΎΠ±Π»ΡΡΡ ΡΡ
ΠΏΠ΅ΡΡΠΏΠ΅ΠΊΡΠΈΠ²Π½ΠΈΠΌΠΈ ΠΊΠ°Π½Π΄ΠΈΠ΄Π°ΡΠ°ΠΌΠΈ Π΄Π»Ρ Π²ΠΈΠΊΠΎΡΠΈΡΡΠ°Π½Π½Ρ Π² ΡΠΊΠΎΡΡΡ Π±Π°Ρ'ΡΡΠ½ΠΈΡ
ΠΌΠ°ΡΠ΅ΡΡΠ°Π»ΡΠ² Π΄Π»Ρ Π·Π°Ρ
ΠΎΡΠΎΠ½Π΅Π½Π½Ρ ΡΠ°Π΄ΡΠΎΠ°ΠΊΡΠΈΠ²Π½ΠΈΡ
Π²ΡΠ΄Ρ
ΠΎΠ΄ΡΠ². ΠΠ΅ΡΠΎΡ ΡΡΡΡ ΡΠΎΠ±ΠΎΡΠΈ Π±ΡΠ»ΠΎ ΠΎΡΡΠΈΠΌΠ°Π½Π½Ρ Π²ΠΈΡΠΎΠΊΠΎΡΡΠ»ΡΠ½ΠΎΡ SiC-ΠΊΠ΅ΡΠ°ΠΌΡΠΊΠΈ Π· Π²Π΄ΠΎΡΠΊΠΎΠ½Π°Π»Π΅Π½ΠΈΠΌΠΈ ΡΡΠ·ΠΈΡΠ½ΠΈΠΌΠΈ Ρ ΠΌΠ΅Ρ
Π°Π½ΡΡΠ½ΠΈΠΌΠΈ Π²Π»Π°ΡΡΠΈΠ²ΠΎΡΡΡΠΌΠΈ. ΠΠΈΡΠΎΠΊΡ ΠΏΠ°ΡΠ°ΠΌΠ΅ΡΡΠΈ ΠΎΡΡΠΈΠΌΠ°Π½ΠΎΡ ΠΊΠ΅ΡΠ°ΠΌΡΠΊΠΈ Π²ΠΈΠ·Π½Π°ΡΠ°ΡΡΡΡΡ ΡΠΎΡΠΌΡΠ²Π°Π½Π½ΡΠΌ Π²ΠΈΡΠΎΠΊΠΎΡΡΠ»ΡΠ½ΠΎΡ Ρ ΠΌΠΎΠ½ΠΎΠ»ΡΡΠ½ΠΎΡ ΡΡΡΡΠΊΡΡΡΠΈ. ΠΠ΅ΡΠ°ΠΌΡΠΊΠ° ΠΊΠ°ΡΠ±ΡΠ΄Ρ ΠΊΡΠ΅ΠΌΠ½ΡΡ ΠΌΠ°Ρ ΠΏΠΎΠ»ΡΠΏΡΠ΅Π½Ρ ΠΌΠ΅Ρ
Π°Π½ΡΡΠ½Ρ ΠΌΡΡΠ½ΡΡΡΡ Ρ Π²ΠΈΡΠΎΠΊΡ ΡΠ²Π΅ΡΠ΄ΡΡΡΡ ΠΏΠΎ ΠΡΠΊΠΊΠ΅ΡΡΡ ΠΏΠΎΡΡΠ΄ΠΊΠ° 28,5 ΠΠa.ΠΠ΅ΡΠΊΠΈΡΠ»ΠΎΡΠΎΠ΄Π½ΡΠ΅ ΠΊΠ΅ΡΠ°ΠΌΠΈΡΠ΅ΡΠΊΠΈΠ΅ ΠΌΠ°ΡΠ΅ΡΠΈΠ°Π»Ρ Π΄Π΅ΠΌΠΎΠ½ΡΡΡΠΈΡΡΡΡ Π²ΡΡΠΎΠΊΠΈΠ΅ ΡΠΈΠ·ΠΈΠΊΠΎ-ΠΌΠ΅Ρ
Π°Π½ΠΈΡΠ΅ΡΠΊΠΈΠ΅ ΡΠ²ΠΎΠΉΡΡΠ²Π°, ΠΊΠΎΡΡΠΎΠ·ΠΈΠΎΠ½Π½ΡΡ ΠΈ ΡΠ°Π΄ΠΈΠ°ΡΠΈΠΎΠ½Π½ΡΡ ΡΡΠΎΠΉΠΊΠΎΡΡΡ, Π΄Π΅Π»Π°ΡΡΠΈΠ΅ ΠΈΡ
ΠΏΠ΅ΡΡΠΏΠ΅ΠΊΡΠΈΠ²Π½ΡΠΌΠΈ ΠΊΠ°Π½Π΄ΠΈΠ΄Π°ΡΠ°ΠΌΠΈ Π΄Π»Ρ ΠΈΡΠΏΠΎΠ»ΡΠ·ΠΎΠ²Π°Π½ΠΈΡ Π² ΠΊΠ°ΡΠ΅ΡΡΠ²Π΅ Π±Π°ΡΡΠ΅ΡΠ½ΡΡ
ΠΌΠ°ΡΠ΅ΡΠΈΠ°Π»ΠΎΠ² Π΄Π»Ρ Π·Π°Ρ
ΠΎΡΠΎΠ½Π΅Π½ΠΈΡ ΡΠ°Π΄ΠΈΠΎΠ°ΠΊΡΠΈΠ²Π½ΡΡ
ΠΎΡΡ
ΠΎΠ΄ΠΎΠ². Π¦Π΅Π»ΡΡ Π½Π°ΡΡΠΎΡΡΠ΅ΠΉ ΡΠ°Π±ΠΎΡΡ Π±ΡΠ»ΠΎ ΠΏΠΎΠ»ΡΡΠ΅Π½ΠΈΠ΅ Π²ΡΡΠΎΠΊΠΎΠΏΠ»ΠΎΡΠ½ΠΎΠΉ SiC-ΠΊΠ΅ΡΠ°ΠΌΠΈΠΊΠΈ Ρ ΡΡΠΎΠ²Π΅ΡΡΠ΅Π½ΡΡΠ²ΠΎΠ²Π°Π½Π½ΡΠΌΠΈ ΡΠΈΠ·ΠΈΡΠ΅ΡΠΊΠΈΠΌΠΈ ΠΈ ΠΌΠ΅Ρ
Π°Π½ΠΈΡΠ΅ΡΠΊΠΈΠΌΠΈ ΡΠ²ΠΎΠΉΡΡΠ²Π°ΠΌΠΈ. ΠΡΡΠΎΠΊΠΈΠ΅ ΠΏΠ°ΡΠ°ΠΌΠ΅ΡΡΡ ΠΏΠΎΠ»ΡΡΠ΅Π½Π½ΠΎΠΉ ΠΊΠ΅ΡΠ°ΠΌΠΈΠΊΠΈ ΠΎΠΏΡΠ΅Π΄Π΅Π»ΡΡΡΡΡ ΡΠΎΡΠΌΠΈΡΠΎΠ²Π°Π½ΠΈΠ΅ΠΌ Π²ΡΡΠΎΠΊΠΎΠΏΠ»ΠΎΡΠ½ΠΎΠΉ ΠΈ ΠΌΠΎΠ½ΠΎΠ»ΠΈΡΠ½ΠΎΠΉ ΡΡΡΡΠΊΡΡΡΡ. ΠΠ΅ΡΠ°ΠΌΠΈΠΊΠ° ΠΊΠ°ΡΠ±ΠΈΠ΄Π° ΠΊΡΠ΅ΠΌΠ½ΠΈΡ ΠΎΠ±Π»Π°Π΄Π°Π΅Ρ ΡΠ»ΡΡΡΠ΅Π½Π½ΠΎΠΉ ΠΌΠ΅Ρ
Π°Π½ΠΈΡΠ΅ΡΠΊΠΎΠΉ ΠΏΡΠΎΡΠ½ΠΎΡΡΡΡ ΠΈ Π²ΡΡΠΎΠΊΠΎΠΉ ΡΠ²Π΅ΡΠ΄ΠΎΡΡΡΡ ΠΏΠΎ ΠΠΈΠΊΠΊΠ΅ΡΡΡ ΠΏΠΎΡΡΠ΄ΠΊΠ° 28,5 ΠΠa
Monte Carlo Methods for Estimating Interfacial Free Energies and Line Tensions
Excess contributions to the free energy due to interfaces occur for many
problems encountered in the statistical physics of condensed matter when
coexistence between different phases is possible (e.g. wetting phenomena,
nucleation, crystal growth, etc.). This article reviews two methods to estimate
both interfacial free energies and line tensions by Monte Carlo simulations of
simple models, (e.g. the Ising model, a symmetrical binary Lennard-Jones fluid
exhibiting a miscibility gap, and a simple Lennard-Jones fluid). One method is
based on thermodynamic integration. This method is useful to study flat and
inclined interfaces for Ising lattices, allowing also the estimation of line
tensions of three-phase contact lines, when the interfaces meet walls (where
"surface fields" may act). A generalization to off-lattice systems is described
as well.
The second method is based on the sampling of the order parameter
distribution of the system throughout the two-phase coexistence region of the
model. Both the interface free energies of flat interfaces and of (spherical or
cylindrical) droplets (or bubbles) can be estimated, including also systems
with walls, where sphere-cap shaped wall-attached droplets occur. The
curvature-dependence of the interfacial free energy is discussed, and estimates
for the line tensions are compared to results from the thermodynamic
integration method. Basic limitations of all these methods are critically
discussed, and an outlook on other approaches is given
Stable interference of EWSβFLI1 in an Ewing sarcoma cell line impairs IGF-1/IGF-1R signalling and reveals TOPK as a new target
BACKGROUND: Ewing sarcoma is a paradigm of solid tumour -bearing chromosomal translocations resulting in fusion proteins that act as deregulated transcription factors. Ewing sarcoma translocations fuse the EWS gene with an ETS transcription factor, mainly FLI1. Most of the EWSβFLI1 target genes still remain unknown and many have been identified in heterologous model systems
Prognostic and predictive value of TOPK stratified by KRAS and BRAF gene alterations in sporadic, hereditary and metastatic colorectal cancer patients
BACKGROUND: Our aim was to investigate the prognostic and predictive value of the oncogenic MAPKK-like protein T-cell-originated protein kinase (TOPK) stratified by KRAS and BRAF mutations in patients with sporadic, hereditary and metastatic colorectal cancer (CRC) treated with anti-EGFR therapy. METHODS: Immunohistochemistry (IHC) for TOPK was performed on four study groups. Group 1 included two subgroups of 543 and 501 sporadic CRC patients used to test the reliability of TOPK expression by IHC. In Group 2, representing an additional 222 sporadic CRCs, the prognostic effect of TOPK stratified by KRAS and BRAF was assessed. The prognostic effect of TOPK was further analysed in Group 3, representing 71 hereditary Lynch syndrome-associated CRC patients. In Group 4, the predictive and prognostic value of TOPK was analysed on 45 metastatic patients treated with cetuximab or panitumumab stratified by KRAS and BRAF gene status. RESULTS: In both sporadic CRC subgroups (Group 1), associations of diffuse TOPK expression with clinicopathological features were reproducible. Molecular analysis of sporadic CRCs in Group 2 showed that diffuse TOPK expression was associated with KRAS and BRAF mutations (p<0.001) and with poor outcome in patients with either mutation in univariate and multivariate analysis (P=0.017). In hereditary patients (Group 3), diffuse TOPK was linked to advanced pT stage. In metastatic patients treated with anti-EGFR therapy (Group 4), diffuse TOPK expression was linked to dismal outcome despite objective response to treatment (P=0.01). CONCLUSIONS: TOPK expression is an unfavourable prognostic indicator in sporadic patients with KRAS or BRAF mutations and also in patients with metastatic disease experiencing a response to anti-EGFR therapies. The inhibition of TOPK, which could benefit 30-40% of CRC patients, may represent a new avenue of investigation for targeted therapy
Outcome in patients perceived as receiving excessive care across different ethical climates: a prospective study in 68 intensive care units in Europe and the USA
Purpose: Whether the quality of the ethical climate in the intensive care unit (ICU) improves the identification of patients receiving excessive care and affects patient outcomes is unknown. Methods: In this prospective observational study, perceptions of excessive care (PECs) by clinicians working in 68 ICUs in Europe and the USA were collected daily during a 28-day period. The quality of the ethical climate in the ICUs was assessed via a validated questionnaire. We compared the combined endpoint (death, not at home or poor quality of life at 1 year) of patients with PECs and the time from PECs until written treatment-limitation decisions (TLDs) and death across the four climates defined via cluster analysis. Results: Of the 4747 eligible clinicians, 2992 (63%) evaluated the ethical climate in their ICU. Of the 321 and 623 patients not admitted for monitoring only in ICUs with a good (n = 12, 18%) and poor (n = 24, 35%) climate, 36 (11%) and 74 (12%), respectively were identified with PECs by at least two clinicians. Of the 35 and 71 identified patients with an available combined endpoint, 100% (95% CI 90.0β1.00) and 85.9% (75.4β92.0) (P = 0.02) attained that endpoint. The risk of death (HR 1.88, 95% CI 1.20β2.92) or receiving a written TLD (HR 2.32, CI 1.11β4.85) in patients with PECs by at least two clinicians was higher in ICUs with a good climate than in those with a poor one. The differences between ICUs with an average climate, with (n = 12, 18%) or without (n = 20, 29%) nursing involvement at the end of life, and ICUs with a poor climate were less obvious but still in favour of the former. Conclusion: Enhancing the quality of the ethical climate in the ICU may improve both the identification of patients receiving excessive care and the decision-making process at the end of life
Effect of SGLT2 inhibitors on stroke and atrial fibrillation in diabetic kidney disease: Results from the CREDENCE trial and meta-analysis
BACKGROUND AND PURPOSE: Chronic kidney disease with reduced estimated glomerular filtration rate or elevated albuminuria increases risk for ischemic and hemorrhagic stroke. This study assessed the effects of sodium glucose cotransporter 2 inhibitors (SGLT2i) on stroke and atrial fibrillation/flutter (AF/AFL) from CREDENCE (Canagliflozin and Renal Events in Diabetes With Established Nephropathy Clinical Evaluation) and a meta-Analysis of large cardiovascular outcome trials (CVOTs) of SGLT2i in type 2 diabetes mellitus. METHODS: CREDENCE randomized 4401 participants with type 2 diabetes mellitus and chronic kidney disease to canagliflozin or placebo. Post hoc, we estimated effects on fatal or nonfatal stroke, stroke subtypes, and intermediate markers of stroke risk including AF/AFL. Stroke and AF/AFL data from 3 other completed large CVOTs and CREDENCE were pooled using random-effects meta-Analysis. RESULTS: In CREDENCE, 142 participants experienced a stroke during follow-up (10.9/1000 patient-years with canagliflozin, 14.2/1000 patient-years with placebo; hazard ratio [HR], 0.77 [95% CI, 0.55-1.08]). Effects by stroke subtypes were: ischemic (HR, 0.88 [95% CI, 0.61-1.28]; n=111), hemorrhagic (HR, 0.50 [95% CI, 0.19-1.32]; n=18), and undetermined (HR, 0.54 [95% CI, 0.20-1.46]; n=17). There was no clear effect on AF/AFL (HR, 0.76 [95% CI, 0.53-1.10]; n=115). The overall effects in the 4 CVOTs combined were: Total stroke (HRpooled, 0.96 [95% CI, 0.82-1.12]), ischemic stroke (HRpooled, 1.01 [95% CI, 0.89-1.14]), hemorrhagic stroke (HRpooled, 0.50 [95% CI, 0.30-0.83]), undetermined stroke (HRpooled, 0.86 [95% CI, 0.49-1.51]), and AF/AFL (HRpooled, 0.81 [95% CI, 0.71-0.93]). There was evidence that SGLT2i effects on total stroke varied by baseline estimated glomerular filtration rate (P=0.01), with protection in the lowest estimated glomerular filtration rate (45 mL/min/1.73 m2]) subgroup (HRpooled, 0.50 [95% CI, 0.31-0.79]). CONCLUSIONS: Although we found no clear effect of SGLT2i on total stroke in CREDENCE or across trials combined, there was some evidence of benefit in preventing hemorrhagic stroke and AF/AFL, as well as total stroke for those with lowest estimated glomerular filtration rate. Future research should focus on confirming these data and exploring potential mechanisms
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