Ocular toxicity associated with anti-HER2 agents in breast cancer: A pharmacovigilance analysis using the FAERS database.

Anti-human epidermal growth factor receptor 2 (HER2) agents have exhibited pronounced tumor-inhibitory activity, yet the accompanying ocular toxicity has frequently been underestimated. We aim to conduct a comprehensive comparative analysis of ocular toxicity risk related to various anti-HER2 agents. We executed a retrospective pharmacovigilance investigation based on the FDA Adverse Event Reporting System (FAERS) database, covering the period from Q2 2018 to Q1 2023. The disproportionality analysis was performed to assess ocular toxicity risk. Multivariate logistic regression was implemented to mitigate potential biases. Moreover, the time to onset of ocular toxicity was also evaluated. A total of 3467 ocular adverse event (AE) reports concerning anti-HER2 agents were collected. At the preferred term (PT) level, there were 69 positive signals, among which excessive eye blinking, abnormal sensation in the eye, and asthenopia presented a significant risk. In comparison to tyrosine kinase inhibitors (TKIs), antibody drugs were associated with a broader range of ocular disorders at Standardized MedDRA Queries (SMQ)levels, including conjunctival disorders, corneal disorders, ocular infections, ocular motility disorders, optic nerve disorders, and retinal disorders. In terms of onset time, pertuzumab displayed an earlier onset at 21.5 days, while trastuzumab deruxtecan had the latest at 91.5 days. In summary, our study reveals varying degrees of ocular toxicity related to anti-HER2 agents, with a significantly higher risk observed in antibody drugs. Additionally, novel ocular toxicity signals, not documented in product labels, have been detected. In the future, further research will be necessary to validate our findings.

Safety, tolerability, and pharmacokinetics of HRS9432(A) injection in healthy Chinese subjects: a phase-I randomized, double-blind, dose escalation, placebo-controlled study.

HRS9432(A) is a long-acting echinocandin antifungal medication primarily used to treat invasive fungal infections, particularly invasive candidiasis. The safety, tolerability, and pharmacokinetic characteristics of HRS9432(A) injection were investigated in a randomized, double-blind, placebo-controlled, single- and multiple-ascending-dose Phase I study involving 56 healthy adult subjects. Doses ranging from 200 to 1200 mg were administered. Safety was continually monitored, including adverse events, clinical laboratory examinations, vital signs, 12-lead electrocardiograms, and physical examinations, while the pharmacokinetic profile within the body was evaluated. The results indicated that concentrations of HRS9432 peaked immediately after infusion, demonstrating essentially linear pharmacokinetic characteristics within the dosage range of 200-1,200 mg. It exhibited a low clearance rate and an extended half-life, with a clearance of approximately 0.2 L/h, a volume of distribution of around 40 L, and a half-life of approximately 140h following a single dose. The accumulation index for AUC0-τ after multiple doses ranged from 1.41 to 1.75. No severe adverse events occurred during the study, and the severity of all adverse events was mild or moderate. Therefore, the intravenous administration of HRS9432(A) in healthy Chinese adult subjects, either as multiple infusions of 200 to 600 mg (once a week, four doses) or as a single infusion of 900-1,200 mg, demonstrated overall good safety and tolerability. The pharmacokinetic exhibited essentially linear characteristics in the body, supporting a weekly dosing frequency for clinical applications and providing additional options for the treatment or prevention of invasive fungal infections. CLINICAL TRIALS: This study is registered with the International Clinical Trials Registry Platform as ChiCTR2300073525.

Designing Different Heterometallic Organic Frameworks by Heteroatom and Second Metal Doping Strategies for the Electrocatalytic Oxygen Evolution Reaction.

Metal-organic frameworks (MOFs) are considered one of the most significant electrocatalysts for the sluggish oxygen evolution reaction (OER). Hence, a series of novel N,S-codoped Ni-based heterometallic organic framework (HMOF) (NiM-bptz-HMOF, M = Co, Zn, and Mn; bptz = 2,5-bis((3-pyridyl)methylthio)thiadiazole) precatalysts are constructed by the heteroatom and second metal doping strategies. The effective combination of the two strategies promotes electronic conductivity and optimizes the electronic structure of the metal. By regulation of the type and proportion of metal ions, the electrochemical performance of the OER can be improved. Among them, the optimized Ni6Zn1-bptz-HMOF precatalyst exhibits the best performance with an overpotential of 268 mV at 10 mA cm-2 and a small Tafel slope of 72.5 mV dec-1. This work presents a novel strategy for the design of modest heteroatom-doped OER catalysts.

An Unusual Crystalline Porous Framework Constructed from Multitypes of Cages with Proton Conduction Property and Heterogeneous Catalytic Activity for Pyrazole Synthesis.

An unusual crystalline porous framework constructed from four types of cages, including all-inorganic Keggin-type polyoxometalate (POM) cages [H3W12O40]5-, organic hexamethylenetetramine (Hmt) cages, nanosized silver-Hmt coordination cages, and giant POM-silver-Hmt cages, was hydrothermally synthesized and structurally characterized. The framework features a highly symmetrical structure with one-dimensional nanoscale channels and holds good thermal/solvent stability, which endow it with proton conduction properties and heterogeneous catalytic activity for pyrazole. This paper not only contributes to broadening the structural diversity of cage-based crystalline porous framework materials but also sheds new light on the design of new functional framework materials.

Two Mn(II)-Bridged Silverton-Type [UMo12O42]8- Polyoxometalates with Catalytic Activity for the Synthesis of Pyrazoles.

Two Mn(II)-bridged Silverton-type {UMo12O42}-based polyoxomolybdates with different three-dimensional structures, Na6(H2O)12[Mn(UMo12O42)] (NaMn) and (NH4)2[K2Na6(µ4-O)2(H2O)1.2Mn(UMo12O42)]·4.6H2O (KMn), were hydrothermally synthesized and further characterized, demonstrating a feasible strategy for the assembly of Silverton-type polyoxomolybdates. Additionally, NaMn is demonstrated to be a good heterogeneous catalyst in the condensation cyclization reaction of hydrazines and 1,3-diketones, and a range of valuable pyrazoles were produced in up to 99% yield.

Transition-Metal Porphyrin-Based MOFs In Situ-Derived Hybrid Catalysts for Electrocatalytic CO2 Reduction.

Excellent electrocatalytic CO2 reduction reaction activity has been demonstrated by transition metals and nitrogen-codoped carbon (M-N-C) catalysts, especially for transition-metal porphyrin (MTPP)-based catalysts. In this work, we propose to use one-step low-temperature pyrolysis of the isostructural MTPP-based metal-organic frameworks (MOFs) and electrochemical in situ reduction strategies to obtain a series of hybrid catalysts of Co nanoparticles (Co NPs) and MTPP, named Co NPs/MTPP (M = Fe, Co, and Ni). The in situ introduction of Co NPs can efficiently enhance the electrocatalytic ability of MTPP (M = Fe, Co, and Ni) to convert CO2 to CO, particularly for FeTPP. Co NPs/FeTPP endowed a high CO faradaic efficiency (FECOmax = 95.5%) in the H cell, and the FECO > 90.0% is in the broad potential range of -0.72 to -1.22 VRHE. In addition, the Co NPs/FeTPP achieved 145.4 mA cm-2 at a lower potential of -0.70 VRHE with an FECO of 94.7%, and the CO partial currents increased quickly to reach 202.2 mA cm-2 at -0.80 VRHE with an FECO of 91.6% in the flow cell. It is confirmed that Co NPs are necessary for hybrid catalysts to get superior electrocatalytic activity; Co NPs also can accelerate H2O dissociation and boost the proton supply capacity to hasten the proton-coupled electron-transfer process, effectively adjusting the adsorption strength of the reaction intermediates.

Two Different Three-Dimensional Uranium-Containing Polymolybdates Based on Zn(II) for the Heterogeneous Catalytic Construction of C-N Bond.

The introduction of transition metal (TM) ions into polyoxometalates (POMs) cannot only bring about interesting structural diversities but also enable changes in properties. However, TM-containing Silverton-type polyoxomolybdates are still lacking in terms of structural diversity and application development. Herein, two Zn(II)-containing Silverton-type {UMo12O42}-based polyoxomolybdates, H1.89Na4.11(H2O)9Zn[UMo12O42]·4.5H2O (Zn-1) and H1.8Na4.2(H2O)12Zn[UMo12O42] (Zn-2) were hydrothermally synthesized, demonstrating a practical strategy to assembly of TM-containing Silverton-type POMs. Zn-1 is proven to be an excellent and recyclable heterogeneous catalyst in cross-dehydrogenation coupling of 1,4-naphthoquinones with amines reactions, and a series of 2-amino-1,4-naphthoquinones with potential medicinal value have been constructed.

Stable Europium(III) Metal-Organic Framework Fluorescence Probe for Intelligent Visualization Detection of Gossypol and Nitrofuran Antibiotics in Real Samples.

Gossypol (Gsp) and antibiotics present in water bodies become organic pollutants that are harmful to human health and the ecological environment. Accurate and effective detection of these pollutants has far-reaching significance in many fields. A new three-dimensional metal-organic framework (MOF), {[Eu3(L)2(HCOO-)(H2O)3]·2H2O·2DMF}n (Eu-MOF), was synthesized from 3,5-bis(2,4-dicarboxylphenyl)nitrobenzene (H4L) ligand and Eu3+ via the solvothermal method in this paper. The Eu-MOF demonstrates strong red fluorescence and can remain stable in different pH solutions. The MOF fluorescence probe could detect organic pollutants through the "shut-off" effect, with a fast response speed and a low detection limit [Gsp, nitrofurantoin (NFT), and nitrofurazone (NFZ) for 0.43, 0.38, and 0.41 µM, respectively]. During the testing process, Eu-MOF exhibited good selectivity and recoverability. Furthermore, the mechanism of fluorescence quenching was investigated, and the recoveries were also good in real samples. This paper introduced a deep learning model to recognize the fluorescence images, a portable intelligent logic detector designed for real-time detection of Gsp by logic gate strategy, and an anticounterfeiting mark prepared based on inkjet printing. Importantly, this work provides a new way of thinking for the detection of organic pollutants in water with high sensitivity and practicality by combining the fluorescence probe with machine learning and logical judgment.

Three Polyoxometalate-Based Ag-Organic Compounds as Heterogeneous Catalysts for the Synthesis of Benzimidazoles.

Three new POM-based compounds, with formulae [Na0.63Ag3(Htba)2.37(tba)0.63(H2O)2(PMo12O40)]·4H2O (Ag3PMo), [Ag4(Htba)4(H2O)2(PMo12O40)](NO3)·H2O (Ag4PMo), and [Ag3(Htba)2(tba)(PW12O40)0.5](NO3)0.5·13H2O (Ag3PW), were prepared with a 3-(4H-1,2,4-triazol-4-yl)benzoic acid (Htba) ligand, Keggin-type anions ([PMo12O40]3-/[PW12O40]3-), and a silver ion (Ag+). The structural features of these compounds are particularly different from the multinuclear subunits, which are [Ag3(tba)3] clusters in Ag3PMo, [Ag4(tba)3] chains in Ag4PMo, and [Ag3(tba)3]2 clusters in Ag3PW, connected by multidonor atom tba ligands and Ag+ ions. Meanwhile, in these compounds, polyanions act as polydentate ligands to link adjacent Ag-tba metal-organic units and expand their spatial dimensions. These compounds, as heterogeneous catalysts, exhibit high stability and excellent catalytic activity to construct benzimidazoles. Ag3PMo could efficiently catalyze the condensation of benzene-1,2-diamines and benzaldehydes and produce benzimidazoles in good yields. In addition, Ag3PMo could be reused up to 7 times and was suitable for gram-scale reactions.

Visible light-mediated synthesis of quinazolinones from benzyl bromides and 2-aminobenzamides without using any photocatalyst or additive.

This paper reports a novel method for the visible-light-mediated synthesis of quinazolinones from the reaction of benzyl bromides with 2-aminobenzamides. The reaction proceeded efficiently at room temperature upon irradiation with an 18 W blue light-emitting diode in air without photocatalysts or additives. By varying the solvent type, substrate molar ratio, and reaction time, the optimal reaction conditions, including the use of methanol solvent, room temperature, and reaction time of 28 h, were identified. Under these conditions, various quinazolinones were obtained using 18 substrates, with the highest yield of 93%. To determine the industrial value of the proposed method, a scale-up reaction was performed and 80% product yield was achieved. Mechanistic studies revealed that the reaction likely proceeded via a radical pathway and that the hydrogen bromide by-product generated during the first step of the reaction of benzyl bromide with 2-aminobenzamide promoted the subsequent step.

Tea polyphenol-derived nanomedicine for targeted photothermal thrombolysis and inflammation suppression.

Thrombotic diseases impose a significant global health burden, and conventional drug-based thrombolytic therapies are encumbered by the risk of bleeding complications. In this study, we introduce a novel drug-free nanomedicine founded on tea polyphenols nanoparticles (TPNs), which exhibits multifaceted capabilities for localized photothermal thrombolysis. TPNs were synthesized through a one-pot process under mild conditions, deriving from the monomeric epigallocatechin-3-gallate (EGCG). Within this process, indocyanine green (ICG) was effectively encapsulated, exploiting multiple intermolecular interactions between EGCG and ICG. While both TPNs and ICG inherently possessed photothermal potential, their synergy significantly enhanced photothermal conversion and stability. Furthermore, the nanomedicine was functionalized with cRGD for targeted delivery to activated platelets within thrombus sites, eliciting robust thrombolysis upon laser irradiation across diverse thrombus types. Importantly, the nanomedicine's potent free radical scavenging abilities concurrently mitigated vascular inflammation, thus diminishing the risk of disease recurrence. In summary, this highly biocompatible multifunctional nanomaterial holds promise as a comprehensive approach that combines thrombolysis with anti-inflammatory actions, offering precision in thrombosis treatment.

Pharmacogenomics and adverse effects of anti-infective drugs in children.

Children, as a special group, have their own peculiarities in terms of individualized medication use compared to adults. Adverse drug reactions have been an important issue that needs to be addressed in the hope of safe medication use in children, and the occurrence of adverse drug reactions is partly due to genetic factors. Anti-infective drugs are widely used in children, and they have always been an important cause of the occurrence of adverse reactions in children. Pharmacogenomic technologies are becoming increasingly sophisticated, and there are now many guidelines describing the pharmacogenomics of anti-infective drugs. However, data from paediatric-based studies are scarce. This review provides a systematic review of the pharmacogenomics of anti-infective drugs recommended for gene-guided use in CPIC guidelines by exploring the relationship between pharmacogenetic frequencies and the incidence of adverse reactions, which will help inform future studies of individualized medication use in children.

Evaluation of bioequivalence and pharmacokinetic profiles for topical desonide cream using Chinese skin.

INTRODUCTION: Skin blanching assay has been established as a surrogate method for assessing bioequivalence of topical corticosteroids. This study aimed to apply the skin blanching assay to evaluate the bioequivalence of a test desonide cream (T) compared with the reference Desonide® (R) using Chinese skins. Additionally, the pharmacokinetics and safety profiles were also assessed. METHODS: By detecting the degree of skin blanching under different dose duration in a pilot dose-duration-response study, the area under the observed effect-time curve (AUEC) and half of the maximum effect (ED50) was calculated. Based on this, the skin color of different time points after a dose duration of ED50, D1 (0.5×ED50) and D2 (2×ED50) were detected as a pharmacodynamic indicator to compare between test and reference creams. A single-center, single-dose, randomized, open-label, two-cycle crossover pharmacokinetic studies were designed to make sure the exposure of tested formulations was not higher than that of the reference formulations. Subjects experiencing adverse events (AEs) were monitored and utilized for safety analysis. RESULTS: These studies involved twelve subjects for the dose-duration-response study, 100 subjects for the bioequivalence study, and twelve subjects for pharmacokinetic study. The results showed that the population ED50 was 0.88±0.45 h, the mean ratio of area under effective curve (AUEC0-24h) of test and reference preparations was 0.95, with a 90% confidence interval as 88.09%-101.72%, indicating the bioequivalence of the test formulation and Desonide®. The maximum concentration (Cmax) and exposure (AUC0-t) of T and R were 20.8 ± 11.5 pg/mL versus 19.7 ± 10.1 pg/mL, respectively, and 451.04 ± 363.65 pg∙h/mL versus 541.47 ± 581.41 pg∙h/mL, respectively. The systemic exposure of a single dose of the test cream was not higher than that of the reference preparation. All of the volunteers experienced grade 1 adverse events (AEs), suggesting that single administration of the test desonide cream is well tolerated in the Chinese healthy population. CONCLUSIONS: This study demonstrated the applicability of skin blanching assay in Chinese skins and established the bioequivalence of test and reference desonide creams.

Co-composting of dewatered sludge and wheat straw with newly isolated Xenophilus azovorans: Carbon dynamics, humification, and driving pathways.

Composting is a biological reaction caused by microorganisms. Composting efficiency can be adequately increased by adding biochar and/or by inoculating with exogenous microorganisms. In this study, we looked at four methods for dewatered sludge waste (DSW) and wheat straw (WS) aerobic co-composting: T1 (no additive), T2 (5% biochar), T3 (5% of a newly isolated strain, Xenophilus azovorans (XPA)), and T4 (5% of biochar-immobilized XPA (BCI-XPA)). Throughout the course of the 42-day composting period, we looked into the carbon dynamics, humification, microbial community succession, and modifications to the driving pathways. Compared to T1 and T2, the addition of XPA (T3) and BCI-XPA (T4) extended the thermophilic phase of composting without negatively affecting compost maturation. Notably, T4 exhibited a higher seed germination index (132.14%). Different from T1 and T2 treatments, T3 and T4 treatments increased CO2 and CH4 emissions in the composting process, in which the cumulative CO2 emissions increased by 18.61-47.16%, and T3 and T4 treatments also promoted the formation of humic acid. Moreover, T4 treatment with BCI-XPA addition showed relatively higher activities of urease, polyphenol oxidase, and laccase, as well as a higher diversity of microorganisms compared to other processes. The Functional Annotation of Prokaryotic Taxa (FAPROTAX) analysis showed that microorganisms involved in the carbon cycle dominated the entire composting process in all treatments, with chemoheterotrophy and aerobic chemoheterotrophy being the main pathways of organic materials degradation. Moreover, the presence of XPA accelerated the breakdown of organic materials by catabolism of aromatic compounds and intracellular parasite pathways. On the other hand, the xylanolysis pathway was aided in the conversion of organic materials to dissolved organics by the addition of BCI-XPA. These findings indicate that XPA and BCI-XPA have potential as additives to improve the efficiency of dewatered sludge and wheat straw co-composting.

Pure separation of acetylene based on a sulfonic acid and amino group functionalized Zn-MOF.

The dual-ligand strategy was employed to synthesize a new microporous material, [Zn3(SNDC)(AmTAZ)3(H2O)]·H2O·CH3CN (1), incorporating sulfonic acid and amino groups for enhancing gas adsorption and separation. The activated 1 (named 1a) exhibited selective adsorption of acetylene over carbon dioxide and methane. Hence, the dual-ligand strategy optimized the pore environment and provided an effective approach for pure separation of gases.

Promising Effects of Montelukast for Critically Ill Asthma Patients via a Reduction in Delirium.

Background: Montelukast (MTK), a potent antagonist of cysteinyl leukotriene receptor 1, has shown therapeutic promise for the treatment of neuropsychiatric disorders. Delirium, a common complication in critically ill patients, lacks effective treatment. This study aims to explore the impact of pre-intensive care unit (ICU) MTK use on in-hospital delirium incidence and, subsequent, prognosis in critically ill patients. Methods: A retrospective cohort study (n = 6344) was conducted using the MIMIC-IV database. After propensity score matching, logistic/Cox regression, E-value sensitivity analysis, and causal mediation analysis were performed to assess associations between pre-ICU MTK exposure and delirium and prognosis in critically ill patients. Results: Pre-ICU MTK use was significantly associated with reduced in-hospital delirium (OR: 0.705; 95% CI 0.497-0.999; p = 0.049) and 90-day mortality (OR: 0.554; 95% CI 0.366-0.840; p = 0.005). The association was more significant in patients without myocardial infarction (OR: 0.856; 95% CI 0.383-0.896; p = 0.014) and could be increased by extending the duration of use. Causal mediation analysis showed that the reduction in delirium partially mediated the association between MTK and 90-day mortality (ACME: -0.053; 95% CI -0.0142 to 0.0002; p = 0.020). Conclusions: In critically ill patients, MTK has shown promising therapeutic benefits by reducing the incidence of delirium and 90-day mortality. This study highlights the potential of MTK, beyond its traditional use in respiratory disease, and may contribute to the development of novel therapeutic strategies for delirium.

[Research progress on immunological properties of ESAT-6 secreted by Mycobacterium tuberculosis and its role in new vaccines].

Early secreted antigenic target of 6 kDa protein (ESAT-6) is the major virulence factor of Mycobacterium tuberculosis (MTB), which can resist the clearance of MTB in bodies by inhibiting macrophage phagocytosis and autophagy reaction, thus impeding the immune defense function of the body against MTB infection. In addition, ESAT-6-induced apoptosis of macrophage and massive necrosis of innate immune cells can foster MTB proliferation and colonization, leading to systemic MTB infection. Moreover, ESAT-6 hampers the protective immune response of Th1 cells, reducing the secretion of pro-inflammatory cytokines and contributing to immune dysfunction, thus accelerating the course of MTB infection. During the process, the high immunogenicity of ESAT-6 can be leveraged as a dominant antigen in the development of new TB vaccines, making it a promising candidate with broad prospects for further development.

Association evaluations of oral anticoagulants with dementia risk based on genomic and real-world data.

BACKGROUND: Several observational studies have suggested that oral anticoagulants (OACs) might reduce the risk of dementia in the elderly, but the evidence is inconclusive. And the consistency of this relationship across different OAC classes and dementia subtypes is still uncertain. METHODS: To comprehensively evaluate this association, we applied Mendelian randomization (MR) combined with pharmacovigilance analysis. MR was used to assess the associations between genetic proxies for three target genes of OACs (VKORC1, F2, and F10) and dementia, including Alzheimer's disease (AD) and vascular dementia (VaD). This genetic analysis was supplemented with real-world pharmacovigilance data, employing disproportionality analysis for more reliable causal inference. RESULTS: Increased expression of the VKORC1 gene was strongly associated with increased risk of dementia, especially for AD (OR = 1.28, 95% CI = 1.14-1.43; p value < 0.001). Based on pharmacovigilance data, vitamin K antagonists (VKAs, inhibitors targeting VKORC1) exhibited a protective effect against dementia risk (ROR = 0.43, 95% CI = 0.28-0.67). Additional sensitivity analyses, including different MR models and cohorts, supported these results. Conversely, no strong causal associations of genetically proxied F2 and F10 target genes with dementia and its subtypes were found. CONCLUSIONS: This study reveals that the inhibition of genetically proxied VKORC1 expression or VKAs exposure is associated with a reduced risk of Alzheimer's dementia. However, there is little evidence to support similar associations with direct oral anticoagulants (F2 inhibitors and F10 inhibitors). Further research is warranted to clinically validate our findings.

ISTransbase: an online database for inhibitor and substrate of drug transporters.

Drug transporters, integral membrane proteins found throughout the human body, play critical roles in physiological and biochemical processes through interactions with ligands, such as substrates and inhibitors. The extensive and disparate data on drug transporters complicate understanding their complex relationships with ligands. To address this challenge, it is essential to gather and summarize information on drug transporters, inhibitors and substrates, and simultaneously develop a comprehensive and user-friendly database. Current online resources often provide fragmented information and have limited coverage of drug transporter substrates and inhibitors, highlighting the need for a specialized, comprehensive and openly accessible database. ISTransbase addresses this gap by amassing a substantial amount of data from literature, government documents and open databases. It includes 16 528 inhibitors and 4465 substrates of 163 drug transporters from 18 different species, resulting in a total of 93 841 inhibitor records and 51 053 substrate records. ISTransbase provides detailed insights into drug transporters and their inhibitors/substrates, encompassing transporter and molecule structure, transporter function and distribution, as well as experimental methods and results from transport or inhibition experiments. Furthermore, ISTransbase offers three search strategies that allow users to retrieve drugs and transporters based on multiple selectable constraints, as well as perform checks for drug-drug interactions. Users can also browse and download data. In summary, ISTransbase (https://istransbase.scbdd.com/) serves as a valuable resource for accurately and efficiently accessing information on drug transporter inhibitors and substrates, aiding researchers in exploring drug transporter mechanisms and assisting clinicians in mitigating adverse drug reactions Database URL: https://istransbase.scbdd.com/.

Cardiovascular Adverse Events Associated with Tumor Necrosis Factor-Alpha Inhibitors: A Real-World Pharmacovigilance Analysis.

AIM: Evidence regarding the association between various tumor necrosis factor-α (TNF-α) inhibitors and cardiovascular adverse events (AEs) is both limited and contradictory. METHODS: A retrospective pharmacovigilance study was conducted using the FDA Adverse Event Reporting System (FAERS) database. Cardiovascular AEs associated with TNF-α inhibitors (adalimumab, infliximab, etanercept, golimumab, and certolizumab) were evaluated using a disproportionality analysis. To reduce potential confounders, adjusted ROR and subgroup analyses were performed. RESULTS: After excluding duplicates, 9,817 cardiovascular reports were associated with the five TNF-α inhibitors. Only adalimumab had positive signals for myocardial infarction (ROR=1.58, 95%CI=1.51-1.64) and arterial thrombosis (ROR=1.54, 95%CI=1.49-1.58). The remaining four TNF-α inhibitors did not show a risk association with any type of cardiovascular event. Further analyses of specific indication subgroups and after adjusting for any confounding factors demonstrated that adalimumab was still significantly associated with cardiovascular events, especially in patients with psoriasis (adjusted ROR=2.16, 95%CI=1.95-2.39). CONCLUSIONS: This study revealed that adalimumab was the only TNF-α inhibitor associated with an elevated risk of thrombotic cardiovascular AEs, whereas the other four TNF-α inhibitors did not show any risk effect. However, given the limitations of such pharmacovigilance studies, it is necessary to validate these findings in prospective studies in the future.