Arabidopsis WRKY55 Transcription Factor Enhances Soft Rot Disease Resistance with ORA59.

Pectobacterium is a major bacterial causal agent leading to soft rot disease in host plants. With the Arabidopsis-Pectobacterium pathosystem, we investigated the function of an Arabidopsis thaliana WRKY55 during defense responses to Pectobacterium carotovorum ssp. carotovorum (Pcc). Pcc-infection specifically induced WRKY55 gene expression. The overexpression of WRKY55 was resistant to the Pcc infection, while wrky55 knockout plants compromised the defense responses against Pcc. WRKY55 expression was mediated via Arabidopsis COI1-dependent signaling pathway showing that WRKY55 can contribute to the gene expression of jasmonic acid-mediated defense marker genes such as PDF1.2 and LOX2. WRKY55 physically interacts with Arabidopsis ORA59 facilitating the expression of PDF1.2</i. Our results suggest that WRKY55 can function as a positive regulator for resistance against Pcc in Arabidopsis.

Effect of Cl2 Radical on Dry Development of Spin-Coated Metal Oxide Resist.

In this study, the effects of Cl2 radicals on dry development of spin-coated metal oxide resist (MOR) and changes in its surface binding states were investigated to verify the mechanism of dry development. Dry development characteristics of tin hydroxide (Tin OH), which is one of the MOR candidates for next generation lithography, were investigated as functions of process time and temperature using a Cl2 radicals source. Non-UV-exposed Tin OH film showed a linear etch rate (1.77 nm/min) from the initial thickness of ∼50 nm, while the UV-exposed film showed slower etch behavior (1.46 nm/min) in addition to the increase of film thickness for up to 3 min during the Cl2 radical dry development. UV-exposed photoresist (PR) contained more oxygen (Sn-O bonding) in the film due to the removal of butyl compounds from the clusters during the UV exposure process. Therefore, due to the lower reaction of chlorine radicals with Sn-O in the UV-exposed Tin OH than the other bindings, the non-UV-exposed PR was preferentially removed compared to the UV-exposed PR. As the temperature decreases, the overall etch rate decreases, but the difference in etch rate between exposed and unexposed Tin OH becomes larger. Finally, at a substrate temperature of -20 °C, the non-UV-exposed Tin OH with a thickness of 50 nm was completely removed, while ∼30 nm thick PR remained for UV-exposed Tin OH. Eventually, a negative tone development was possible with Cl2 radical plasma due to the difference in activation energy between the UV-exposed and non-UV-exposed films. It is believed that dry development using Cl2 radicals will be one of the most important process techniques for next-generation patterning to remove problems such as pattern leaning, line edge roughness, residue, etc., caused by wet development.

Effect of Bias Frequency on Bottom-Up SiO2 Gap-Filling Using Plasma-Enhanced Atomic Layer Deposition.

High-aspect-ratio patterns are required for next-generation three-dimensional (3D) semiconductor devices. However, it is challenging to eliminate voids and seams during gap-filling of these high-aspect-ratio patterns, such as deep trenches, especially for nanoscale high-aspect-ratio patterns. In this study, a SiO2 plasma-enhanced atomic layer deposition process incorporated with ion collision using bias power to the substrate was used for bottom-up trench gap-filling. The effect of bias power frequency on SiO2 trench gap-filling was then investigated. Results showed that changes in bias power frequency did not significantly change the process rate, such as SiO2 growth per cycle. At relatively low bias power frequencies, high-energy ions formed an overhang at the entrance of the high-aspect-ratio trench pattern through sputter etching and redeposition, blocking the pattern entrance. However, at relatively high-frequency bias power, overhang formation due to sputtering did not occur. In the trench interior, due to a scattering effect of ions, deposition was thicker at the bottom of the trench than that at the top, achieving bottom-up gap-filling and void-free gap-filling.

Plasma enhanced atomic layer deposition of silicon nitride using magnetized very high frequency plasma.

To obtain high-quality SiNxfilms applicable to an extensive range of processes, such as gate spacers in fin field-effect transistors (FinFETs), the self-aligned quadruple patterning process, etc, a study of plasma with higher plasma density and lower plasma damage is crucial in addition to study on novel precursors for SiNxplasma-enhanced atomic layer deposition (PEALD) processes. In this study, a novel magnetized PEALD process was developed for depositing high-quality SiNxfilms using di(isopropylamino)silane (DIPAS) and magnetized N2plasma at a low substrate temperature of 200 °C. The properties of the deposited SiNxfilms were analyzed and compared with those obtained by the PEALD process using a non-magnetized N2plasma source under the same conditions. The PEALD SiNxfilm, produced using an external magnetic field (ranging from 0 to 100 G) during the plasma exposure step, exhibited a higher growth rate (∼1 Å/cycle) due to the increased plasma density. Additionally, it showed lower surface roughness, higher film density, and enhanced wet etch resistance compared to films deposited using the PEALD process with non-magnetized plasmas. This improvement can be attributed to the higher ion flux and lower ion energy of the magnetized plasma. The electrical characteristics, such as interface trap density and breakdown voltage, were also enhanced when the magnetized plasma was used for the PEALD process. Furthermore, when SiNxfilms were deposited on high-aspect-ratio (30:1) trench patterns using the magnetized PEALD process, an improved step coverage of over 98% was achieved, in contrast to the conformality of SiNxdeposited using non-magnetized plasma. This enhancement is possibly a result of deeper radical penetration enabled by the magnetized plasma.

Application of entire dental panorama image data in artificial intelligence model for age estimation.

BACKGROUND: Accurate age estimation is vital for clinical and forensic purposes. With the rapid advancement of artificial intelligence(AI) technologies, traditional methods relying on tooth development, while reliable, can be enhanced by leveraging deep learning, particularly neural networks. This study evaluated the efficiency of an AI model by applying the entire panoramic image for age estimation. The outcome performances were analyzed through supervised learning (SL) models. METHODS: Total of 27,877 dental panorama images from 5 to 90 years of age were classified by 2 types of grouping. In type 1 they were classified by each age and in type 2, applying heuristic grouping, the age over 20 years were classified by every 5 years. Wide ResNet (WRN) and DenseNet (DN) were used for supervised learning. In addition, the analysis with ± 3 years of deviation in both types were performed. RESULTS: For the DN model, while the type 1 grouping achieved an accuracy of 0.1016 and F1 score of 0.058, the type 2 achieved an accuracy of 0.3146 and F1 score of 0.2027. Incorporating ± 3years of deviation, the accuracy of type 1 and 2 were 0.281, 0.7323 respectively; and the F1 score were 0.1768, 0.6583 respectively. For the WRN model, while the type 1 grouping achieved an accuracy of 0.1041 and F1 score of 0.0599, the type 2 achieved an accuracy of 0.3182 and F1 score of 0.2071. Incorporating ± 3years of deviation, the accuracy of type 1 and 2 were 0.2716, 0.7323 respectively; and the F1 score were 0.1709, 0.6437 respectively. CONCLUSIONS: The application of entire panorama image data for supervised with classification by heuristics grouping with ± 3years of deviation for supervised learning models and demonstrated satisfactory outcome for the age estimation.

Highly selective etching of SiNxover SiO2using ClF3/Cl2remote plasma.

Highly selective etching of silicon nitride over silicon oxide is one of the most important processes especially for the fabrication of vertical semiconductor devices including 3D NAND (Not And) devices. In this study, isotropic dry etching characteristics of SiNxand SiO2using ClF3/Cl2remote plasmas have been investigated. The increase of Cl2percent in ClF3/Cl2gas mixture increased etch selectivity of SiNxover SiO2while decreasing SiNxetch rate. By addition of 15% Cl to ClF3/Cl2, the etch selectivity higher than 500 could be obtained with the SiNxetch rate of ∼8 nm min-1, and the increase of Cl percent to 20% further increased the etch selectivity to higher than 1000. It was found that SiNxcan be etched through the reaction from Si-N to Si-F and Si-Cl (also from Si-Cl to Si-F) while SiO2can be etched only through the reaction from Si-O to Si-F, and which is also in extremely low reaction at room temperature. When SiNx/SiO2layer stack was etched using ClF3/Cl2(15%), extremely selective removal of SiNxlayer in the SiNx/SiO2layer stack could be obtained without noticeable etching of SiO2layer in the stack and without etch loading effect.

Plasma Enhanced Atomic Layer Deposition of Silicon Nitride for Two Different Aminosilane Precursors Using Very High Frequency (162 MHz) Plasma Source.

Plasma enhanced atomic layer deposition (PEALD) of silicon nitride (SiNx) using very high frequency (VHF, 162 MHz) plasma source was investigated at the process temperatures of 100, 200, and 300 °C. Two aminosilane precursors having different numbers of amino ligands, bis(tert-butylamino)silane (BTBAS) and di(sec-butylamino)silane (DSBAS), were used as Si precursors. A comparative study was also conducted to verify the effect of the number of amino ligands on the properties of SiNx film. At all process temperatures, DSBAS, having one amino ligand, performed better than BTBAS in various aspects. SiNx films deposited using DSBAS had lower surface roughness, higher film density, lower wet etch rate, improved electrical characteristics, and higher growth rate than those deposited using BTBAS. With the combination of a VHF plasma source and DSBAS with one amino ligand, the SiNx films grown at 300 °C exhibited low wet etch rates (≤2 nm/min) in a dilute HF solution (100:1 of deionized water:HF) as well as low C content below the XPS detection limit. Also, excellent step coverage close to 100% on high aspect ratio (30:1) trench structures was obtained by using VHF plasma, which could provide sufficient flux of plasma species inside the trenches in conjunction with DSBAS having fewer amino ligands than BTBAS.

The efficacy of supervised learning and semi-supervised learning in diagnosis of impacted third molar on panoramic radiographs through artificial intelligence model.

OBJECTIVES: The aim of the study was to evaluate the efficacy of traditional supervised learning (SL) and semi-supervised learning (SSL) in the classification of mandibular third molars (Mn3s) on panoramic images. The simplicity of preprocessing step and the outcome of the performance of SL and SSL were analyzed. METHODS: Total 1625 Mn3s cropped images from 1000 panoramic images were labeled for classifications of the depth of impaction (D class), spatial relation with adjacent second molar (S class), and relationship with inferior alveolar nerve canal (N class). For the SL model, WideResNet (WRN) was applicated and for the SSL model, LaplaceNet (LN) was utilized. RESULTS: In the WRN model, 300 labeled images for D and S classes, and 360 labeled images for N class were used for training and validation. In the LN model, only 40 labeled images for D, S, and N classes were used for learning. The F1 score were 0.87, 0.87, and 0.83 in WRN model, 0.84, 0.94, and 0.80 for D class, S class, and N class in the LN model, respectively. CONCLUSIONS: These results confirmed that the LN model applied as SSL, even utilizing a small number of labeled images, demonstrated the satisfactory of the prediction accuracy similar to that of the WRN model as SL.

Ameliorative Effects of Flavonoids from Platycodon grandiflorus Aerial Parts on Alloxan-Induced Pancreatic Islet Damage in Zebrafish.

Platycodon grandiflorus (balloon flower), used as a food reserve as well as in traditional herbal medicine, is known for its multiple beneficial effects. In particular, this plant is widely used as a vegetable in Republic of Korea. We examined the ameliorative effects of P. grandiflorus on alloxan-induced pancreatic islet damage in zebrafish. The aerial part treatment led to a significant recovery in pancreatic islet size and glucose uptake. The efficacy of the aerial part was more potent than that of the root. Eight flavonoids (1-8) were isolated from the aerial part. Structures of two new flavone glycosides, designated dorajiside I (1) and II (2), were elucidated to be luteolin 7-O-α-L-rhamno-pyranosyl (1 → 2)-(6-O-acetyl)-ß-D-glucopyranoside and apigenin 7-O-α-L-rhamnopyranosyl (1 → 2)-(6-O-acetyl)-ß-D-glucopyranoside, respectively, by spectroscopic analysis. Compounds 1, 3, 4 and 6-8 yielded the recovery of injured pancreatic islets in zebrafish. Among them, compound 7 blocked KATP channels in pancreatic ß-cells. Furthermore, compounds 3, 4, 6 and 7 showed significant changes with respect to the mRNA expression of GCK, GCKR, GLIS3 and CDKN2B compared to alloxan-induced zebrafish. In conclusion, the aerial part of P. grandiflorus and its constituents conferred a regenerative effect on injured pancreatic islets.

Synthesis and evaluation of ent-Conduramine C-1 derivatives as α-glucosidase inhibitors via CSI-mediated amination reaction.

Concise synthesis of ent-conduramine C-1 and its derivatives has been achieved by using commercially available d-ribose. The key steps in the synthesis are regioselective and diastereoselective amination of polybenzyl ethers by chlorosulfonyl isocyanate (CSI), chelation-controlled carbonyl addition, and intramolecular olefin metathesis. All of the synthesized compounds were evaluated for inhibitory activity against α-glucosidase. The derivatives 18 (IC50 = 0.65 ± 0.03 mM) and 19 (IC50 = 0.26 ± 0.01 mM) were identified to be more potent than well-known α-glucosidase inhibitor acarbose (IC50 = 1.05 ± 0.17 mM) as a positive control.

Synthesis and biological evaluation of novel N-benzyltriazolyl-hydroxamate derivatives as selective histone deacetylase 6 inhibitors.

Histone deacetylases (HDAC) regulate post-translational acetylation and the inhibition of these enzymes has emerged as an intriguing disease therapeutic. Among them, class IIb HDAC6 has the unique characteristic of mainly deacetylating cytoplasmic proteins, suggesting clinical applications for neurodegenerative diseases, inflammation, and cancer. In this study, we designed a novel N-benzyltriazolyl-hydroxamate scaffold based on the known HDAC6 inhibitors nexturastat A and tubastatin A. Among the 27 derivatives, 3-fluoro-4-((3-(2-fluorophenyl)-1H-1,2,4-triazol-1-yl)methyl)-N-hydroxybenzamide 4u (HDAC6 IC50 = 7.08 nM) showed nanomolar HDAC6 inhibitory activity with 42-fold selectivity over HDAC1. Structure-activity relationship (SAR) and computational docking studies were conducted to optimize the triazole capping group. Docking analysis revealed that the capping group aligned with the conserved L1 pocket of HDAC6 and was associated with subtype selectivity. Overall, our study explored the triazole-based biaryl capping group and its substitution and orientation, suggesting a rationale for the design of HDAC6-selective inhibitors.

A resveratrol oligomer, hopeaphenol suppresses virulence activity of Pectobacterium atrosepticum via the modulation of the master regulator, FlhDC.

Pectobacterium atrosepticum (P. atrosepticum: Pba) which causes potato soft rot and blackleg is a notorious plant pathogen worldwide. Discovery of new types of antimicrobial chemicals that target specifically to virulence factors such as bacterial motility and extracellular enzymes is required for protecting crops from pathogenic infection. A transcriptomic analysis of Pba upon hopeaphenol treatment revealed that bacterial motility-related gene expression, including a master regulator flhDC genes, was significantly influenced by hopeaphenol. We further generated a double knock-out mutant of flhDC genes by CRISPR/Cas9 system and confirmed phenotypic changes in bacterial motility, transcription of extracellular enzymes, and disease development consistent with the result of wild-type treated with hopeaphenol. The hopeaphenol-treated Pba strains, wild-type, double mutant, and complemented strain were unable to secrete the enzymes in vitro, while ΔflhDC double mutant strain reduced the secretion. Thus, our study supports that FlhDC is essential for the virulence of Pba, and proposes that hopeaphenol modulates FlhDC-dependent virulence pathways, suggesting a potential of hopeaphenol as an anti-virulence agent to manage potato soft rot and blackleg diseases.

Resveratrol Oligomers, Plant-Produced Natural Products With Anti-virulence and Plant Immune-Priming Roles.

Antibiotic resistance has become increasingly prevalent in the environment. Many alternative strategies have been proposed for the treatment and prevention of diverse diseases in agriculture. Among them, the modulation of bacterial virulence to bypass antibiotic resistance or boost plant innate immunity can be considered a promising drug target. Plant-produced natural products offer a broad spectrum of stereochemistry and a wide range of pharmacophores, providing a great diversity of biological activities. Here, we present a perspective on the putative role of plant-produced resveratrol oligomers as anti-virulence and plant-immune priming agents for efficient disease management. Resveratrol oligomers can decrease (1) bacterial motility directly and (2) indirectly by attenuating the bacterial type III secretion system (TT3S). They induce enhanced local immune responses mediated by two-layered plant innate immunity, demonstrating (3) a putative plant immune priming role.

Selective etching of silicon nitride over silicon oxide using ClF3/H2 remote plasma.

Precise and selective removal of silicon nitride (SiNx) over silicon oxide (SiOy) in a oxide/nitride stack is crucial for a current three dimensional NOT-AND type flash memory fabrication process. In this study, fast and selective isotropic etching of SiNx over SiOy has been investigated using a ClF3/H2 remote plasma in an inductively coupled plasma system. The SiNx etch rate over 80 nm/min with the etch selectivity (SiNx over SiOy) of ~ 130 was observed under a ClF3 remote plasma at a room temperature. Furthermore, the addition of H2 to the ClF3 resulted in an increase of etching selectivity over 200 while lowering the etch rate of both oxide and nitride due to the reduction of F radicals in the plasma. The time dependent-etch characteristics of ClF3, ClF3 & H2 remote plasma showed little loading effect during the etching of silicon nitride on oxide/nitride stack wafer with similar etch rate with that of blank nitride wafer.

Deposition of Very-Low-Hydrogen-Containing Silicon at a Low Temperature Using Very-High-Frequency (162 MHz) SiH4 Plasma.

Low-hydrogen-containing amorphous silicon (a-Si) was deposited at a low temperature of 80 °C using a very high frequency (VHF at 162 MHz) plasma system with multi-split electrodes. Using the 162 MHz VHF plasma system, a high deposition rate of a-Si with a relatively high deposition uniformity of 6.7% could be obtained due to the formation of high-ion-density (>1011 cm-3) plasma with SiH4 and a lack of standing waves by using small multi-split electrodes. The increase in the radio frequency (RF) power decreased the hydrogen content in the deposited silicon film and, at a high RF power of 2000 W, a-Si with a low hydrogen content of 3.78% could be deposited without the need for a dehydrogenation process. The crystallization of the a-Si by ultraviolet (UV) irradiation showed that the a-Si can be crystallized with a crystallinity of 0.8 and a UV energy of 80 J without dehydrogenation. High-resolution transmission electron microscopy showed that the a-Si deposited by the VHF plasma was a very small nanocrystalline-like a-Si and the crystalline size significantly grew with the UV irradiation. We believe that the VHF (162 MHz) multi-split plasma system can be used for a low-cost low-temperature polysilicon (LTPS) process.

Clinical Outcomes of Secondary Prophylactic Granulocyte Colony-Stimulating Factors in Breast Cancer Patients at a Risk of Neutropenia with Doxorubicin and Cyclophosphamide-Based Chemotherapy.

Doxorubicin and cyclophosphamide (AC)-based chemotherapy has been a standard regimen for early-stage breast cancer (ESBC) with an intermediate risk (10-20%) of febrile neutropenia (FN). Secondary prophylaxis of granulocyte colony-stimulating factor (G-CSF) is considered in patients receiving AC-based chemotherapy; however, relevant studies are limited. Here, we retrospectively reviewed the electronic medical records of 320 patients who completed adjuvant AC-based chemotherapy from September 2016 to September 2020. Approximately 46.6% of the patients developed severe neutropenic events (SNE) during AC-based chemotherapy. Secondary prophylaxis of G-CSF reduced the risk of recurrent SNE (p < 0.01) and the relative dose intensity (RDI) < 85% (p = 0.03) in patients who had experienced SNE during AC-based chemotherapy. Age ≥ 65 years (p = 0.02) and alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 60 IU/L (p = 0.04) were significant risk factors for RDI < 85%. The incidences of FN, grade 4 neutropenia, unscheduled hospitalization, and interruption to the dosing regimen were reduced in patients administered secondary prophylaxis with G-CSF (before vs. after administration: FN, 19.4% vs. 4.6%; grade 4 neutropenia, 86.1% vs. 14.8%; unscheduled hospitalization, 75.9% vs. 11.1%; interruption to the dosing regimen, 18.5% vs. 8.3%). This study indicated the importance of active intervention of G-CSF use to prevent recurrent SNE and improve clinical outcomes in patients with breast cancer who receive AC-based chemotherapy.

Reduction of EUV resist damage by neutral beam etching.

Even though EUV lithography has the advantage of implenting a finer pattern compared to ArF immersion lithography due to the use of 13.5 nm instead of 193 nm as the wavelength of the light source, due to the low energy of EUV light source, EUV resist has a thinner thickness than conventional ArF resist. EUV resist having such a thin thickness is more vulnerable to radiation damage received during the etching because of its low etch resistance and also tends to have a problem of low etch selectivity. In this study, the radiation damage to EUV resist during etching of hardmask materials such as Si3N4, SiO2, etc using CF4gas was compared between neutral beam etching (NBE) and ion beam etching (IBE). When NBE was used, after the etching of 20 nm thick EUV resist, the line edge roughness increase and the critical dimension change of EUV resist were reduced by ∼1/3 and ∼1/2, respectively, compared to those by IBE. Also, at that EUV etch depth, the root mean square surface roughness value of EUV resist etched by NBE was ∼2/3 compared to that by IBE on the average. It was also confirmed that the etching selectivity between SiO2, Si3N4, etc and EUV resist was higher for NBE compared to IBE. The less damage to the EUV resist and the higher etch selectivity of materials such as Si3N4and SiO2over EUV resist for NBE compared to IBE are believed to be related to the no potential energy released by the neutralization of the ions during the etching by NBE.

Role of Recent Therapeutic Applications and the Infection Strategies of Shiga Toxin-Producing Escherichia coli.

Shiga toxin-producing Escherichia coli (STEC) is a global foodborne bacterial pathogen that is often accountable for colon disorder or distress. STEC commonly induces severe diarrhea in hosts but can cause critical illnesses due to the Shiga toxin virulence factors. To date, there have been a significant number of STEC serotypes have been evolved. STECs vary from nausea and hemorrhoid (HC) to possible lethal hemolytic-based uremic syndrome (HUS), thrombotic thrombocytopenic purpura (TTP). Inflammation-based STEC is usually a foodborne illness with Shiga toxins (Stx 1 and 2) thought to be pathogenesis. The STEC's pathogenicity depends significantly on developing one or more Shiga toxins, which can constrain host cell protein synthesis leading to cytotoxicity. In managing STEC infections, antimicrobial agents are generally avoided, as bacterial damage and discharge of accumulated toxins are thought the body. It has also been documented that certain antibiotics improve toxin production and the development of these species. Many different groups have attempted various therapies, including toxin-focused antibodies, toxin-based polymers, synbiotic agents, and secondary metabolites remedies. Besides, in recent years, antibiotics' efficacy in treating STEC infections has been reassessed with some encouraging methods. Nevertheless, the primary role of synbiotic effectiveness (probiotic and prebiotic) against pathogenic STEC and other enteropathogens is less recognized. Additional studies are required to understand the mechanisms of action of probiotic bacteria and yeast against STEC infection. Because of the consensus contraindication of antimicrobials for these bacterial pathogens, the examination was focused on alternative remedy strategies for STEC infections. The rise of novel STEC serotypes and approaches employed in its treatment are highlighted.

Broad-Spectrum Antibiotic Regimen Affects Survival in Patients Receiving Nivolumab for Non-Small Cell Lung Cancer.

Antibiotic-induced dysbiosis may affect the efficacy of immune checkpoint inhibitors. We investigated the impact of antibiotics on the clinical outcomes of nivolumab in patients with non-small cell lung cancer (NSCLC). Patients who received nivolumab for NSCLC between July 2015 and June 2018 and who were followed up until June 2020 were included in a retrospective cohort analysis. Of 140 eligible patients, 70 were on antibiotics. Overall survival (OS) was shorter in patients on antibiotics (ABX) compared to those not on antibiotics (NoABX) (p = 0.014). OS was negatively associated with piperacillin/tazobactam (PTZ) (HR = 3.31, 95% CI: 1.77-6.18), days of therapy (DOT) ≥ 2 weeks (HR = 2.56, 95% CI: 1.30-5.22) and DOT of PTZ. The defined daily dose (DDD) in PTZ (r = 0.27) and glycopeptides (r = 0.21) showed weak correlations with mortality. There was no difference in progression-free survival (PFS) between ABX and NoABX; however, PFS was negatively associated with the antibiotic class PTZ and DOT of PTZ. Therefore, the use of a broad-spectrum antibiotic, such as PTZ, the long-term use of antibiotics more than 2 weeks in total and the large amount of defined daily dose of specific antibiotics were associated with decreased survival in patients receiving nivolumab for NSCLC.

P2Y12 Antiplatelet Choice for Patients with Chronic Kidney Disease and Acute Coronary Syndrome: A Systematic Review and Meta-Analysis.

This study aims to evaluate potentially appropriate antiplatelet therapy in patients with chronic kidney disease. A systematic analysis was conducted to identify the clinical outcomes of available antiplatelet therapy regimens with enhanced platelet inhibition activity (intervention of 5 regimens) over the standard dose of clopidogrel-based dual antiplatelet therapy in patients with renal insufficiency. An electronic keyword search was performed on Pubmed, Embase, and Cochrane Library per PRISMA guidelines. We performed a prespecified net clinical benefit analysis (a composite of the rates of all-cause or cardiac-related death, myocardial infarction, major adverse cardiac outcomes, and minor and major bleeding), and included 12 studies. The intervention substantially lowered the incidence of all-cause mortality (RR 0.67; p = 0.003), major adverse cardiac outcomes (RR 0.79; p < 0.00001), and myocardial infarction (RR 0.28; p = 0.00007) without major bleeding (RR 1.14; p = 0.33) in patients with renal insufficiency, but no significant differences were noticed with cardiac-related mortality and stent thrombosis. The subgroup analysis revealed substantially elevated bleeding risk in patients with severe renal insufficiency or on hemodialysis (RR 1.68; p = 0.002). Our study confirmed that the intervention considerably enhances clinical outcomes in patients with renal insufficiency, however, a standard dose of clopidogrel-based antiplatelet therapy is favorable in patients with severe renal insufficiency.