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ObjectiveOpen microsurgery, often with bypass techniques, is indispensable for complex aneurysms. To date, it remains unknown whether arterial anatomy or quantitative blood flow measurements can predict insufficient flow-related stroke (IRS). The present study aimed to evaluate the risk factors for IRS in patients treated with open microsurgery with bypass procedures for complex internal carotid artery aneurysms.MethodsPatients with complex aneurysms undergoing bypass surgery were retrospectively reviewed. The recipient/donor flow index (RDFI) was preoperatively evaluated using colour-coding angiography. RDFI was defined as the ratio of the cerebral blood volume of the recipient and donor arteries. The sizes of the recipient and donor arteries were measured. The recipient/donor diameter index (RDDI) was then calculated. IRS was defined as the presence of new postoperative neurological deficits and infarction on postoperative CT scans. We assessed the association between RDFI and other variables and the IRS.ResultsTwenty patients (38±12 years) were analysed. IRS was observed in 12 patients (60%). Patients with postoperative IRS had a higher RDFI than those without postoperative IRS (p2.3 were more likely to develop IRS (pConclusionQuantitative digital subtraction angiography enables preoperative evaluation of cerebral blood volume. RDFI >2.3, rather than RDDI, was significantly associated with postoperative IRS. This preoperative evaluation allows appropriate decisions regarding the treatment strategy for preventing postoperative IRS.

Recently, great progress has been made in the field of Few-Shot Learning (FSL). While many different methods have been proposed, one of the key factors leading to higher FSL performance is surprisingly simple. It is the backbone network architecture used to embed the images of the few-shot tasks. While first works on FSL resorted to small architectures with just a few convolution layers, recent works show that large architectures pre-trained on the training portion of FSL datasets produce strong features that are more easily transferable to novel few-shot tasks, thus attaining significant gains to methods using them. Despite these observations, little to no work has been done towards finding the right backbone for FSL. In this paper we propose MetAdapt that not only meta-searches for an optimized architecture for FSL using Network Architecture Search (NAS), but also results in a model that can adaptively ‘re-wire’ itself predicting the better architecture for a given novel few-shot task. Using the proposed approach we observe strong results on two popular few-shot benchmarks: miniImageNet and FC100.

Synthesis of high-efficiency, cost-effective, and stable photocatalysts has long been a priority for sustainable photocatalytic CO

Background Sepsis is a life-threatening disease with a limited effectiveness and the potential mechanism remains unclear. LncRNA NEAT-2 plays an important role in tumor proliferation, invasion and metastasis, and also involved in the regulation of cardiovascular disease. This study aimed to investigate the function of NEAT-2 in sepsis. Methods We built sepsis animal model with Male Balb/C mice induced by cecal ligation and puncture (CLP). A total of 54 mice were randomly assigned into eight groups: sham operation group (n = 18), CLP group (n = 18), CLP plus si-control group (n = 3), CLP plus si-NEAT2 group (n = 3), CLP plus mimic control group (n = 3), CLP plus miR-320 group (n = 3), CLP plus normal saline group (n = 3), and normal control group (n = 3). The number of peripheral endothelial progenitor cells (EPCs), the expression level of NEAT-2 and miR-320 were detected during progression of sepsis, as well as the number of peripheral EPCs and level of TNF-α, IL-6, VEGF, ALT, AST and Cr. In addition, the function of EPCs was evaluated after NEAT-2 knockdown and miR-320 overexpression in vitro. Results The number of circulating EPCs increased significantly in sepsis. NEAT-2 expression was significantly increased in the progress of sepsis, accompanied with miR-320 downregulated. NEAT-2 knockdown and miR-320 overexpression attenuated hepatorenal function and increased cytokines in sepsis. Moreover, NEAT-2 knockdown and miR-320 overexpression decreased the proliferation, migration and angiogenesis of endothelial progenitor cells in vitro. Conclusions LncRNA-NEAT2 regulated the number and function of endothelial progenitor cells via miR-320 in sepsis.

Objectives Exposure to light at night (LAN) can disturb circadian endocrine and metabolic rhythms. Hyperuricemia (HUA) is an early-onset metabolic disorder. However, it is still not clear whether LAN exposure increases the prevalence of HUA. Material and Methods The authors used crosssectional data on the Beijing-Tianjin-Hebei occupational populations cohort from March–July 2017. A total of 7664 steel workers were finally selected to investigate the relationship between LAN exposure and the prevalence of HUA among steel workers. The authors collected demographic and socio-economic data, as well as information on lifestyle factors, anthropometric measures, and laboratory tests. The restricted cubic spline method was used to analyze the dose-response relationship between cumulative LAN exposure and the prevalence of HUA. Logistic regression analyses were used to fit the relationship between them. Results The average age of the participants was 43.5±8.6 years; 7051 (91.7%) of them were males, 2749 (35.9%) reported to suffer from HUA, and 1241 (16.2%) were not exposed to LAN. There was a significant non-linear dose-response relationship between them. After adjustment for the confounding factors, including demographic data, lifestyle factors, etc., the lower LAN exposure was significantly associated with HUA (0–1931.7 days, OR = 1.180, and the 95% CI: 1.000–1.394; 1931.7–4343 days, OR = 1.215, 95% CI: 1.035–1.426). Conclusions This study revealed that a certain amount of exposure to LAN is independently related to the prevalence of HUA in steel workers in China. Int J Occup Med Environ Health. 2021;34(3):385–401

Background Intralenticular foreign body is rarely encountered in ophthalmic practice. In most cases, subsequent traumatic cataract requires cataract surgery for visual rehabilitation. Case summary A 35-year-old man was injured by iron filings in his left eye. After the injury, the patient tried to draw the object out by himself using a magnet; however, the foreign body (FB) was pushed to the equator of the lens. The FB was removed by a magnet through the anterior chamber accessed through the original capsular wound. Since most of the lens was transparent and only partially opaque after the operation, the lens was kept under close observation. After the surgery, the patient's visual acuity reached 20/20 from 2/20, visual function recovered very well, and local opacity of the lens remained stable. Conclusion For intralenticular FB in the anterior cortex under the capsule, magnet may be a more advantageous way to remove the object.

AIMS The therapeutic effect of plasma exchange (PLEX) combined with conventional treatment in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) remains controversial. MATERIALS AND METHODS We searched PubMed, Embase, Cochrane Library, and China National Knowledge Infrastructure for randomized controlled trials (RCTs) and cohort studies that compared PLEX added to conventional therapy with conventional therapy only in active AAV. RESULTS 19 studies were included for the meta-analysis. Compared with the conventional therapy group, the PLEX group had a significantly reduced risk of end-stage renal disease (ESRD) at 3 months (odds ratio (OR) = 0.32, 95% confidence interval (CI) = 0.16 - 0.66, p = 0.002, I2 = 0%), and the ANCA titerwas also decreased (OR = 40.99, 95% Cl = 23.56 - 58.43, p

BACKGROUND: To investigate the performance of a radiomics model based on gray-scale ultrasonography (US) for the preoperative non-invasive prediction of ipsilateral axillary lymph node (ALN) metastasis in patients with breast cancer (BC). METHODS: A total of 192 pathologically confirmed BC patients were included in this study. The training set was comprised of 132 patients from hospital 1 and the test set was comprised of 60 patients from hospital 2. All patients underwent US before percutaneous core biopsy and the results of ALN status reported by a radiologist with 12 years of experience were recorded. Radiomic features were extracted from the gray-scale US images. Max-relevance and min-redundancy (MRMR) and least absolute shrinkage and selection operator (LASSO) were used for data dimension reduction and feature selection. A radiomics model was constructed using LASSO and was validated using the leave group out cross-validation (LGOCV) method. The performance of the model was validated with receiver operating characteristic (ROC), calibration curve, and decision curve analysis. RESULTS: A total of 860 features were extracted from the gray-scale US images of each breast lesion, and 9 radiomic features were selected for model construction. The area under the curve (AUC), sensitivity, and specificity of the model for predicting ALN metastasis were 0.85, 78.9%, and 77.3% in the training set and 0.65, 68.0%, and 79.4% in the test set, respectively. The prediction performance of the model was significantly higher than that of the radiologist (AUC: 0.85 vs. 0.59, P0.05) in the test set. CONCLUSIONS: The non-invasive radiomics model has the ability to predict ALN metastasis for patients with breast cancer and may outperform US-reported ALN status performed by the radiologist.

Fusarium wilt is a devastating disease which impacts watermelon production. Soil fumigation using dazomet followed by biological organic fertilizer was applied to suppress the Fusarium wilt disease. We propose that fumigation suppresses the soil indigenous community, especially the soil-borne pathogens, while the utilization of bio-organic fertilizer facilitates the recovery of the soil microbiome to a beneficial, suppressive state through the introduction of plant growth-promoting microorganisms. Greenhouse experiment showed that applied biological organic fertilizer after dazomet fumigation effective restrain the disease incidence with a 93.6% disease control. Fumigation strongly decreased soil microbial diversity and altered relative taxa abundances, suggesting the possibility of niche release by the resident soil microbial community. Fumigation followed by bio-fertilizer transformed the soil microbial community composition and resulted in higher relative abundances of beneficial microbial groups such as Bacillus (8.5%) and Trichoderma (13.5%), coupled with lower Fusarium abundance compared to other treatments. Network analysis illustrated that soil fumigation decreased interactions within the soil microbial community with less nodes and links while bio-fertilizer addition promoted node interactions. In addition, bio-fertilizer addition after fumigation resulted in the beneficial species becoming the key network connectors. Collectively, fumigation appears to release the resident soil niche resulting in lower diversity while the beneficial microbes introduced by bio-fertilizer addition colonize these niches, leading to a more complex community with fewer pathogens that suppresses Fusarium wilt disease incidence.

Frequent use of insecticide causes an environmental hazard, and also leads pest to develop insecticide resistance. Enhancement of metabolic detoxification and reduction of target sensitivity are the primary mechanism of insecticide resistance. Clarifying the regulatory pathway of resistance mechanism states a pivotal theoretical foundation of delaying insecticide resistance development. Here, we show that three endogenous microRNAs, PC-3p-2522_840, PC-3p-446_6601 and PC-5p-3096_674, are required for the small brown planthopper (SBPH) to modulate triflumezopyrim tolerance via activating pathways of three metabolic detoxification phases. Twenty-one down-regulated miRNAs were acquired, and PC-5p-3096_674, PC-3p-446_6601 and PC-3p-2522_840 were the three most significantly down-regulated miRNAs during triflumezopyrim exposure. The mortality of SBPH was significantly increased after over-supplementation of PC-5p-3096_674, PC-3p-446_6601 and PC-3p-2522_840, with triflumezopyrim exposure. Moreover, the interactions between PC-3p-2522_840 and cytochrome P450 CYP6FL1, PC-3p-446_6601 and glutathione S-transferase GSTD2, UDP-Glycosyltransferase UGT386F1, PC-5p-3096_674 and ATP-binding cassette transporters ABCA3 were systematically demonstrated through the dual luciferase reporter assay. Besides, the mortality of SBPH was significantly increased after knockdown of CYP6FL1, GSTD2, UGT386F1 and ABCA3 with triflumezopyrim exposure. These findings uncover a strategy whereby the SBPH weakens three endogenous microRNAs to activate pathways of three metabolic detoxification phases via targeting CYP6FL1, GSTD2, UGT386F1 and ABCA3 and promotes its tolerance to triflumezopyrim.

To investigate the effect of acute graft-versus-host disease (aGVHD) mouse models established respectively by total body irradiation (TBI) and busulfan combined with cyclophosphamide (BU/CY) conditioning regimens after allogeneic hematopoietic stem cell transplantation (allo-HSCT).Bone marrow cells and splenic mononuclear cells were isolated respectively from femur, tibia, and spleen of C57BL/6 male mice (H-2Kb) which were selected as donors. After TBI pretreatment, BALB/c female mice (H-2Kd) were injected with donor bone marrow cells 1×10Both TBI and BU/CY as conditioning regimens can successfully establish stable mouse models of aGVHD after fully allo-HSCT and haploidentical HSCT for further research about mechanism of aGVHD. BU/CY conditioning regimen can more truly simulate physiological status in vivo of patients with chemotherapy based conditioning regimen, while TBI conditioning regimen shows significantly more typical aGVHD symptoms and easier to operate.TBI与BU/CY两种预处理方案建立急性移植物抗宿主病小鼠模型的比较.分别使用全身照射（TBI）与白消安联合环磷酰胺（BU/CY）两种预处理方案建立异基因造血干细胞移植后的急性移植物抗宿主病（aGVHD）小鼠模型，并探讨两种预处理方案建立aGVHD小鼠模型的效果.以C57BL/6雄性小鼠（H-2Kb）为供鼠，分离股骨、胫骨骨髓细胞及脾单个核细胞，使用TBI预处理BALB/c雌性小鼠（H-2Kd），同时使用BU/CY方案预处理CB6F1雌性小鼠（H-2Kd/b）后，两组小鼠经尾静脉分别注射供鼠骨髓细胞1×10两组小鼠移植后均出现精神萎靡、活动度下降、体重连续下降，以及不同程度的脱 毛、弓背体位、腹泻及肛门肿胀等aGVHD表现，所有小鼠在4周内全部死亡；流式细胞术检测结果显示，两组小鼠移植后均完全嵌合；病理检查显示，小鼠皮肤、肠道、肝脏、肺和脾等靶器官组织可见明显的aGVHD病理学改变。TBI组小鼠较BU/CY组小鼠表现出更为明显的体重下降、大面积脱毛及皮肤皱褶等典型体征，aGVHD评分显著高，两组比较差异有统计学意义（P0.05）.TBI与BU/CY两种预处理方案可成功构建稳定的完全异基因造血干细胞移植与半相合骨髓移植后aGVHD模型，采用BU/CY预处理方案可更真实地模拟目前临床上更为常用的化疗为主的预处理方案的患者体内的生理状态，而TBI预处理方案的小鼠具有更为典型的aGVHD表现，操作更为简便，两种方案均可为后续研究aGVHD发生相关机制提供可靠的临床前模型.

Introduction: Foreign bodies (FBs) in the external auditory canal (EAC) are common in pediatric otorhinolaryngology. Although clinicians have tried many methods and tools to treat these patients, removing the spherical FBs embedded deep in EAC is still a challenge. Occasionally successful removal of such FBs requires local or general anesthesia. Case Presentation: Here, we developed a simple and novel 3-dimensional (3D) printing tool to successfully treat a child suffering from a spherical FB in EAC. The child received no further treatment, and no complications developed afterward. Conclusions: It is challenging to remove spherical FBs in EAC. We developed a tiny, safe, and cheap tool to treat a child with such a FB in EAC. The clinical outcome was satisfactory.

The formation and metabolic balance of bone tissue is a controllable process of biomineralization, which is regulated by various cells, biomolecules, and ions. Enzyme molecules play an important role in this process, and alkaline phosphatase (ALP) is one of the most critical factors. In this study, inspired by the process of bone biomineralization, a biomimetic strategy is achieved for the preparation of mineralized ALP nanoparticles (MALPNs), by taking advantages of the unique reaction between ALP and calcium ions in Dulbecco's modified Eagle's medium. Benefiting from the mild biomineralization reaction, the MALPN system highly maintains the activity of ALP. Furthermore, the in vitro studies show that the MALPN system significantly enhances the proliferation of bone marrow mesenchymal stem cells and upregulates their osteogenic differentiation. When evaluated as synthetic graft materials for bone regeneration, the MALPN-incorporated gelatin methacryloyl graft shows excellent mechanical properties, a sustained release profile of ALP, and high biocompatibility and efficacy in guiding bone regeneration and vascularization for critical-sized rat calvarial defect. Moreover, we also demonstrate that the biomimetic mineralization strategy can be adopted for other proteins such as acid phosphatase, bovine serum albumin, fibrinogen, and gelatin, suggesting its universality for constructing mineralized protein-/enzyme-based bioactive materials for the application of tissue regeneration.

This study aimed to investigate the diagnostic value of corneal anterior, posterior, and total higher-order aberrations in keratoconic eyes.We enrolled 94 patients (152 eyes) with mild keratoconus (Group 1), 64 patients (101 eyes) with moderate keratoconus (Group 2), and 32 patients (52 eyes) with advanced keratoconus (Group 3) according to the Amsler-Krumeich classification system; 99 healthy controls (197 normal eyes) were likewise enrolled. Anterior, posterior, and total corneal higher-order aberrations were assessed using a rotating Scheimpflug camera. The 3rd-order and 4th-order root-mean-square values were calculated for higher-order aberrations, including coma, spherical, and trefoil aberrations. Differences between keratoconic and normal eyes were analyzed using Kruskal-Wallis tests. Receiver operating characteristic curves were evaluated for the keratoconus and control groups.The differences in coma 90, coma, trefoil, and spherical aberrations, as well as 3rd-order and 4th-order root-mean-square values, were statistically significant between the keratoconus and control groups for all anterior, posterior, and corneal aberrations. The absolute values of these higher-order aberrations were higher in the keratoconus groups than in the control group and increased with keratoconus severity in Groups 1-3. Coma and 3rd-order RMS values showed excellent sensitivity and specificity for discriminating between normal and keratoconus eyes for all anterior, posterior, and corneal aberrations.Coma aberrations and 3rd-order root-mean-square values may be valuable for diagnosing keratoconus. Combining these data with topography information may enable the effective and efficient detection of keratoconus in the future.

The heavy-metal adsorbent ε-MnO

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is an autoimmune disease often accompanied by rapidly progressive renal failure, and the genetic background is still unknown. Our study was performed to test whether autophagy-related 16 like 1 (ATG16L1) rs4663402 and rs4663396 single nucleotide polymorphisms (SNPs) were associated with AAV in the Chinese Guangxi population.One hundred seventy seven unrelated AAV patients and 216 healthy controls were included in this case-control study. Multiplex polymerase chain reaction combined with high-throughput sequencing was used for typing, and SNPStats and SHEsis were used for association analysis, pairwise linkage disequilibrium, and haplotype analysis.rs4663402 and rs4663396 were in Hardy-Weinberg equilibrium in AAV and control groups. The frequencies of rs4663402 AA, AT, and TT genotypes were 82.5%, 16.9%, and 0.6%, respectively, in patients with AAV, and 83.5%, 16.2%, and 0.5%, respectively, in controls. The frequencies of rs4663396 CC, CT, and TT genotypes were 63.8%, 33.9%, and 2.3%, respectively, in patients with AAV, and 69.2%, 26.6%, and 4.2%, respectively, in controls. Haplotype analysis revealed two SNPs in a single haplotype block (D' = 1.0). Our logistic regression adjusted for sex and age showed no association between rs4663402 and rs4663396 and the risk for AAV in genetic models (p 0.05). However, ATG16L1 rs4663396 CC and CT + TT genotypes exhibited statistically significant differences in the incidence of arthralgia (p = 0.03).Our results indicated that ATG16L1 rs4663402 and rs4663396 polymorphisms were not associated with AAV in the Chinese Guangxi population. ATG16L1 rs4663396 CT + TT genotype may be associated with arthralgia.

To explore whether the post-left atrium space (PLAS) ratio would be useful for prenatal diagnosis of total anomalous pulmonary venous connection (TAPVC) using echocardiography and artificial intelligence.We retrospectively included 642 frames of four-chamber views from 319 fetuses (32 with TAPVC and 287 without TAPVC) in end-systolic and end-diastolic periods with multiple apex directions. The average gestational age was 25.6 ± 2.7 weeks. No other cardiac or extracardiac malformations were observed. The dataset was divided into a training set (n = 540; 48 with TAPVC and 492 without TAPVC) and test set (n = 102; 20 with TAPVC and 82 without TAPVC). The PLAS ratio was defined as the ratio of the epicardium-descending aortic distance to the center of the heart-descending aortic distance. Supervised learning was used in DeepLabv3+, FastFCN, PSPNet, and DenseASPP segmentation models. The area under the curve (AUC) was used on the test set.Expert annotations showed that this ratio was not related to the period or apex direction. It was higher in the TAPVC group than in the control group detected by the expert and the four models. The AUC of expert annotations, DeepLabv3+, FastFCN, PSPNet, and DenseASPP were 0.977, 0.941, 0.925, 0.856, and 0.887, respectively.Segmentation models achieve good diagnostic accuracy for TAPVC based on the PLAS ratio.

Quantitative protein mapping on whole-tissue levels provides important insights into the spatially-organized regulatory processes/networks related to diseases and therapy, but remains a tremendous challenge. We describe a micro-scaffold assisted spatial proteomics(MASP) method, based on precise tissue spatial-compartmentalization using a 3D-printed micro-scaffold, capable of mapping thousands of proteins across a whole-tissue slice with excellent quantitative quality. The mapping accuracy was validated and applied in mapping > 5,000 cerebral proteins in mouse brain.

In this paper, a mathematical model for simulating the grain evolution process of ceramic materials was constructed to investigate the effects of the sintering parameters on the microstructure in the spark plasma sintering process. Firstly, a new algorithm of removing the right angle of grain was improved and an improved cell state assignment method was proposed based on the cellular automata model. Then the sintering parameters were coupled into the model, and the simulation method of grain growth and pore evolution were proposed. Finally, a ceramic material grain evolution model with stomata structure for spark plasma sintering was constructed. The simulation results showed that the grain size increased exponentially with the increases of holding time and sintering temperature, while the pores gradually decreased with the increase of the two parameters and the density of the material. Besides, the uniformity of grain growth also decreased with the increase of holding time. These results conformed to the topological characteristics of grain growth and the law of grain boundary migration, and can provide support for the sintering parameters optimization of ceramic tool materials.

In this work, a hierarchical porous SnS2/rGO/TiO2 hollow sphere heterojunction that allows highly-efficient light utilization and shortening distance of charge transformation is rationally designed and synthesized. More importantly, an rGO interlayer is successfully embedded between the TiO2 hollow sphere shells and outermost SnS2 nanosheets. This interlayer functions as a bridge to connect the two light-harvesting semiconductors and acts as a hole injection layer in the tandem heterojunction. The induced built-in electric fields on both sides of the interface precisely regulate the spatial separation and directional migration of the photo-generated holes from the light-harvesting semiconductor to the rGO hole injection interlayer. These synergistic effects greatly prolong the lifetime of the photo-induced charge carriers. The optimized tandem heterojunction with a 2 wt% rGO loading demonstrate enhanced visible-light-driven photocatalytic activity for Rhodamine B (RhB) dye degradation (removal rate: 97.3%) and Cr(VI) reduction (removal rate: 97.09%). This work reveals a new strategy for the rational design and assembly of hollow-structured photocatalytic materials with spatially separated reduction and oxidation surfaces to achieve excellent photocatalytic performance.

l-carnitine is an amino acid derivative that is thought to be helpful for treating renal anemia in hemodialysis patients. However, the mechanism remains to be fully elucidated. A literature search was performed on PubMed, Embase, and Cochrane Central Register of Controlled Trials to identify randomized controlled trials (RCTs) and conduct a meta-analysis for investigating the effect of l-carnitine in the treatment of renal anemia in participants receiving hemodialysis. A total of 18 eligible trials with 1090 participants were included in this study. l-carnitine can significantly increase plasma free l-carnitine levels (mean difference [MD]: 140.53, 95% confidence interval [CI] 102.22–178.85; P

A study was conducted to determine whether iron-based phosphate binders (IBPBs) need to be preferred for hyperphosphatemia and anemia management in patients on dialysis. For this meta-analysis, we searched PubMed, Embase, and Cochrane Central Register of Controlled Trials for randomized controlled trials that evaluated the efficacy and safety of IBPBs in decreasing phosphate and correcting anemia in dialysis patients. Nineteen trials comprising 4719 participants were included. Compared with placebo, serum phosphate decreased significantly after treatment with ferric citrate (FC), fermagate (one study), and SBR759 (one study). Hemoglobin increased significantly after treatment with FC and sucroferric oxyhydroxide (PA21). In addition, FC and PA21 reduced serum intact parathyroid hormone (iPTH) and increased ferritin and transferrin saturation, but SBR759 did not. Compared with active treatment, the non-inferiority of IBPBs in reducing serum phosphate and iPTH was demonstrated. FC significantly improved serum hemoglobin and iron-related parameters and decreased the use of intravenous iron and erythropoiesis-stimulating agent, whereas PA21 did not increase serum hemoglobin level. The incidences of infection and hospitalization were similar between the two groups, with FC having a higher risk of diarrhea than the placebo and active treatments. FC was associated with the control of hyperphosphatemia and the improvement of anemia. However, PA21 did not show superiority for alleviating anemia compared with the active treatment. Other IBPBs, such as fermagate and SBR759, remained poorly understood due to the limited number of studies. Further trials are required to assess the effect of IBPBs on the risk of cardiovascular events and all-cause mortality.