Efficacy and safety of GST-HG171 in adult patients with mild to moderate COVID-19: a randomised, double-blind, placebo-controlled phase 2/3 trial.

Background: GST-HG171 is a potent, broad-spectrum, orally bioavailable small-molecule 3C like protease inhibitor that has demonstrated greater potency and efficacy compared to Nirmatrelvir in pre-clinical studies. We aimed to evaluate the efficacy and safety of orally administered GST-HG171 plus Ritonavir in patients with coronavirus disease 2019 (COVID-19) infected with emerging XBB and non-XBB variants. Methods: This randomised, double-blind, placebo-controlled phase 2/3 trial was conducted in 47 sites in China among adult patients with mild-to-moderate COVID-19 with symptoms onset ≤72 h. Eligible patients were randomised 1:1 to receive GST-HG171 (150 mg) plus Ritonavir (100 mg) or corresponding placebo tablets twice daily for 5 days, with stratification factors including the risk level of disease progression and vaccination status. The primary efficacy endpoint was time to sustained recovery of clinical symptoms within 28 days, defined as a score of 0 for 11 COVID-19-related target symptoms for 2 consecutive days, assessed in the modified intention-to-treat (mITT) population. This trial was registered at ClinicalTrials.gov (NCT05656443) and Chinese Clinical Trial Registry (ChiCTR2200067088). Findings: Between Dec 19, 2022, and May 4, 2023, 1525 patients were screened. Among 1246 patients who underwent randomisation, most completed basic (21.2%) or booster (74.9%) COVID-19 immunization, and most had a low risk of disease progression at baseline. 610 of 617 who received GST-HG171 plus Ritonavir and 603 of 610 who received placebo were included in the mITT population. Patients who received GST-HG171 plus Ritonavir showed shortened median time to sustained recovery of clinical symptoms compared to the placebo group (13.0 days [95.45% confidence interval 12.0-15.0] vs. 15.0 days [14.0-15.0], P = 0.031). Consistent results were observed in both SARS-CoV-2 XBB (45.7%, 481/1053 of mITT population) and non-XBB variants (54.3%, 572/1053 of mITT population) subgroups. Incidence of adverse events was similar in the GST-HG171 plus Ritonavir (320/617, 51.9%) and placebo group (298/610, 48.9%). The most common adverse events in both placebo and treatment groups were hypertriglyceridaemia (10.0% vs. 14.7%). No deaths occurred. Interpretation: Treatment with GST-HG171 plus Ritonavir has demonstrated benefits in symptom recovery and viral clearance among low-risk vaccinated adult patients with COVID-19, without apparent safety concerns. As most patients were treated within 2 days after symptom onset in our study, confirming the potential benefits of symptom recovery for patients with a longer duration between symptom onset and treatment initiation will require real-world studies. Funding: Fujian Akeylink Biotechnology Co., Ltd.

Olgotrelvir, a dual inhibitor of SARS-CoV-2 Mpro and cathepsin L, as a standalone antiviral oral intervention candidate for COVID-19.

BACKGROUND: Oral antiviral drugs with improved antiviral potency and safety are needed to address current challenges in clinical practice for treatment of COVID-19, including the risks of rebound, drug-drug interactions, and emerging resistance. METHODS: Olgotrelvir (STI-1558) is designed as a next-generation antiviral targeting the SARS-CoV-2 main protease (Mpro), an essential enzyme for SARS-CoV-2 replication, and human cathepsin L (CTSL), a key enzyme for SARS-CoV-2 entry into host cells. FINDINGS: Olgotrelvir is a highly bioavailable oral prodrug that is converted in plasma to its active form, AC1115. The dual mechanism of action of olgotrelvir and AC1115 was confirmed by enzyme activity inhibition assays and co-crystal structures of AC1115 with SARS-CoV-2 Mpro and human CTSL. AC1115 displayed antiviral activity by inhibiting replication of all tested SARS-CoV-2 variants in cell culture systems. Olgotrelvir also inhibited viral entry into cells using SARS-CoV-2 Spike-mediated pseudotypes by inhibition of host CTSL. In the K18-hACE2 transgenic mouse model of SARS-CoV-2-mediated disease, olgotrelvir significantly reduced the virus load in the lungs, prevented body weight loss, and reduced cytokine release and lung pathologies. Olgotrelvir demonstrated potent activity against the nirmatrelvir-resistant Mpro E166 mutants. Olgotrelvir showed enhanced oral bioavailability in animal models and in humans with significant plasma exposure without ritonavir. In phase I studies (ClinicalTrials.gov: NCT05364840 and NCT05523739), olgotrelvir demonstrated a favorable safety profile and antiviral activity. CONCLUSIONS: Olgotrelvir is an oral inhibitor targeting Mpro and CTSL with high antiviral activity and plasma exposure and is a standalone treatment candidate for COVID-19. FUNDING: Funded by Sorrento Therapeutics.

Mpox patients' experience from infection to treatment and implications for prevention and control: A multicenter qualitative study in China.

Monkeypox (mpox), a viral zoonotic disease, is spreading worldwide. However, evidence that informs prevention and control strategies in the Asia Pacific Region is very limited. Our study aims to investigate the experiences of mpox patients from infection to treatment to provide scientific basis for the prevention and control. A multicenter qualitative design was used. A total of 15 mpox patients were recruited between July 6 and July 25, 2023, from six cities in China. Semistructured interviews were conducted by telephone and analyzed using the thematic analysis. The interview was divided into two sections: patients' experiences (prediagnosis experience, treatment-seeking experience, and quarantine experience) and advice. Prediagnosis experience was summarized into three themes: symptoms, possible routes of infection, and knowledge of mpox. Treatment-seeking experience was summarized into three themes: time of visit to hospital, diagnostic difficulties, and attitude toward diagnosis. Quarantine experience was summarized into three themes: body and mind reactions, reluctance to self-disclose infection status, and factors facilitating recovery. Themes identified from patients' advice were as follows: (1) Increase in testing channels and methods, (2) Development and introduction of vaccines, (3) Adjustment of quarantine program, (4) Improvement of treatment measures, and (5) Improvement of publicity and education. To effectively curb the mpox epidemic, structured measures are urgently needed to address the mpox-related stigma and discrimination. Targeted health education should be provided to MSM, focusing on the prevention, detection, and treatment services. Hospitals should enhance the training of clinicians in key departments including infectious disease and dermatology, to improve diagnostic capability and sensitivity. Furthermore, given the absence of specific antiviral medications, supervised home quarantine may be a good option.

Epidemiological characteristics, clinical manifestations, and mental health status of human mpox cases: A multicenter cross-sectional study in China.

Human mpox is occurring worldwide, however, evidence from the Asian Pacific Region is limited. In this multicenter cross-sectional study, information of confirmed mpox cases diagnosed between June 1 and July 31, 2023 in China. Information included demographic and epidemiological characteristics, and clinical manifestations, laboratory results, and mental health status of mpox cases. A total of 115 confirmed mpox cases were enrolled. All cases were men. A total of 102 (90.3%) identified as homosexual. The median age was 31.0 years (interquartile range 27.0-36.5). A total of 65 (56.5%) were HIV-positive, of whom 92.3% were receiving antiretroviral therapy (ART). A total of 19/39 (40.4%) had a CD4 cell count <500 cells/µL. Systemic features such as fever (73.0%), lymphadenopathies (49.6%), and myalgia (28.7%) were commonly observed. Skin lesions were present in all participants: 49.6% in the genital area and 27.0% in the perianal area. Vesicular rash (78.3%) and papular rash (44.3%) were the most common lesion morphologies. People living with HIV were more likely to have anxiety than those living without HIV. The majority of mpox cases had primary genital lesions and sexual activities before diagnosis, which supports the likelihood of sexual contact transmission. Guidelines on hospitalization and isolation protocols for mpox patients necessitate further confirmation.

Hyperglycosylated N-Linked Site 339 of gp120 Appears to Be Unique and May Contribute to CRF01_AE Transmission Among Men Who Have Sex with Men in China and Thailand.

Human immunodeficiency virus (HIV)-1 CRF01_AE is one of the most important genotypes in China, especially in the population of men who have sex with men (MSM). It has become the most prevalent strain among them. Describing the variant characterization of CRF01_AE will help to reveal the reason behind its predominance in MSM. In this study, the complete DNA sequences (CDSs) for gp120 from the envelope protein (env) gene of CRF01_AE in China and Thailand were retrieved from the Los Alamos HIV database. The CDSs for gp120 were divided into three subgroups according to the risk factors for HIV-1 transmission in a variety of populations, such as intravenous drug users (IDU), heterosexual contacts (HC), and MSM. The N-linked CDS glycosylation sites for gp120 in CRF01_AE were analyzed. The results showed a unique hyperglycosylation site N-339 (refer to Hxb2) in the gp120 of CRF01_AE in MSM compared with the IDU and HC groups from China. The result was the same in the MSM group from Thailand, which suggests that the hyperglycosylation site N-339 may explain the widespread CRF01_AE genotype in MSM.

Rational Design and Characterization of Trispecific Antibodies Targeting the HIV-1 Receptor and Envelope Glycoprotein.

Multitudinous broadly neutralizing antibodies (bNAbs) against HIV-1 have been developed as novel antiviral prophylactic and therapeutic agents. Combinations of bNAbs are generally even more effective than when they are applied individually, showing excellent neutralization coverage and limiting the emergence of escape mutants. In this study, we investigated the design and characterization of three trispecific antibodies that allow a single molecule to interact with independent HIV-1 envelope determinants-(1) the host receptor CD4, (2) the host co-receptor CCR5 and (3) distinct domains in the envelope glycoprotein of HIV-1-using an ELISA, an HIV-1 pseudovirus neutralization assay and in vivo antiviral experiments in humanized mice. We found that trispecific bNAbs and monovalent ones all had satisfactory binding activities against the corresponding antigens in the ELISA, exhibited higher potency and breadth than any previously described single bnAb in the HIV-1 pseudovirus neutralization assay and showed an excellent antiviral effect in vivo. The trispecific antibodies simultaneously recognize the host receptor CD4, host co-receptor CCR5 and HIV-1 envelope glycoprotein, which could mean they have promise as prophylactic and therapeutic agents against HIV-1.

Analysis of 394 COVID-19 cases infected with Omicron variant in Shenzhen: impact of underlying diseases to patient's symptoms.

OBJECTIVES: The emergence of new variants of SARS-CoV-2 is continuously posing pressure to the epidemic prevention and control in China. The Omicron variant of SARS-CoV-2 having stronger infectivity, immune escape ability, and capability causing repetitive infection spread to many countries and regions all over the world including South Africa, United States and United Kingdom etc., in a short time. The outbreaks of Omicron variant also occurred in China. The aim of this study is to understand the epidemiological characteristics of Omicron variant infection in Shenzhen and to provide scientific basis for effective disease control and prevention. METHODS: The clinical data of 394 imported COVID-19 cases infected with Omicron variant from 16 December 2021 to 24 March 2022 admitted to the Third People's hospital of Shenzhen were collected and analyzed retrospectively. Nucleic acid of SARS-CoV-2 of nasopharyngeal swabs and blood samples was detected using 2019-nCoV nucleic acid detection kit. Differences in Ct values of N gene were compared between mild group and moderate group. The specific IgG antibody was detected using 2019-nCoV IgG antibody detection kit. Statistical analysis was done using SPSS software and graphpad prism. RESULTS: Patients were categorized into mild group and moderate group according to disease severity. The data on the general conditions, underlying diseases, COVID-19 vaccination and IgG antibody, viral load, laboratory examination results, and duration of hospitalization, etc., were compared among disease groups. Mild gorup had higher IgG level and shorter nucleic acid conversion time. Patients with underlying diseases have 4.6 times higher probability to progress to moderate infection. CONCLUSION: In terms of epidemic prevention, immunization coverage should be strengthened in the population with underlying diseases. In medical institutions, more attention needs to be paid to such vulnerable population and prevent further deterioration of the disease.

A baseline epidemiological study of the co-infection of enteric protozoans with human immunodeficiency virus among men who have sex with men from Northeast China.

BACKGROUND: Human immunodeficiency virus (HIV) and enteric parasite co-infection not only aggravates the clinical symptoms of parasites but also accelerates acquired immunodeficiency syndrome (AIDS) progression. However, co-infection research on men who have sex with men (MSM), the predominant high-risk population of HIV/AIDS in China, is still limited. In this study, we investigated the epidemiology of enteric parasites, risk factors, and associations with clinical significance in an MSM HIV/AIDS population in Heilongjiang Province, northeast China. METHODS: We recruited 308 MSMs HIV/AIDS patients and 199 HIV-negative individuals in two designated AIDS hospitals in Heilongjiang between April 2016 and July 2017. Fresh stool samples were collected. DNA extraction, molecular identification, and genotyping of Cryptosporidium species, Entamoeba histolytica, Cyclospora cayetanensis, Enterocytozoon bieneusi, and Blastocystis hominis were performed. Fourteen diarrhea-related pathogens were examined to exclude the influence of other bacterial pathogens on diarrhea incidence. RESULTS: 31.5% of MSM HIV/AIDS participants were infected with at least one parasite species, a significantly higher proportion than that found in the HIV-negative individuals (2.5%). E. bieneusi presented the highest prevalence, followed by B. hominis, E. histolytica, Cryptosporidium spp., and C. cayetanensis. Warm seasons were the risk factor for parasitic infections in this population [odds ratio (OR) = 2.6, 95% CI: 1.47-4.57]. In addition, these individuals showed a higher proportion (35.8%) of present diarrhea (PD) compared with men who have sex with women (MSW) with HIV/AIDS (16.7%). The infection proportions of both Cryptosporidium spp. and E. histolytica were significantly higher in the PD. E. bieneusi infection was more prevalent in the historic diarrhea (HD) group. CD4+ T cell counts in the MSM patients with the above three parasites were significantly lower. New species and genotypes were found, and MSM patients had a wider range of species or genotypes. CONCLUSIONS: Enteric parasitic infection was prevalent in the MSM HIV/AIDS population, especially in patients with present diarrhea during warm seasons. E. histolytica and B. hominis should also be considered high-risk parasites for opportunistic infections in AIDS patients in addition to Cryptosporidium spp.

Critical amino acid residues and potential N-linked glycosylation sites contribute to circulating recombinant form 01_AE pathogenesis in Northeast China.

OBJECTIVE: The current study aimed to understand epidemiological feature and critical factors associated with pathogenesis of circulating recombinant form (CRF) 01_AE strains in Northeast China. DESIGN: Compared analysis was made between CRF01_AE and non-CRF01_AE samples to understand the pathogenicity features of CRF01_AE. Further analyses between CRF01_AE samples with high or low CD4 cell counts and between samples with different coreceptor usages were done to explore the possible factors correlating to the pathogenesis of CRF01_AE viruses. METHODS: The genotypes of newly identified strains were determined by phylogenetic analyses using Mega 6.06. Coreceptor usage was predicted by Geno2Pheno algorithm. Potential N-linked glycosylation site (PNGS) number was calculated using the online N-glycosite software. The properties of amino acid sequences were analyzed by the online ProtParam tool. RESULTS: CRF01_AE become the main HIV-1 genotype since 2010. Compared with non-CRF01_AE group, the CRF01_AE group showed a higher proportion of samples with CD4 cell count less than 200 cells/µl. Shorter amino acid length, fewer PNGSs and the presence of a basic motif R/KNXT or NR/KT in V4 correlated to a lower CD4 cell count, and existence or coexistence of Thr12, Arg13, Val21 and Lys33, presence of more than 4 of net charges and lack of the PNGS within V3 favored to the X4/R5X4 coreceptor usage of CRF01_AE viruses. CONCLUSION: CRF01_AE has dominated HIV-1 genotype in Northeast China. Infection with CRF01_AE exhibited a fast disease progression, which may be associated with specific amino acid residues and PNGSs in V3 and V4 regions as well as amino acid length of V4 region.

Discovery of potential therapeutic targets for non-small cell lung cancer using high-throughput metabolomics analysis based on liquid chromatography coupled with tandem mass spectrometry.

Lung cancer is a severe health problem and threatens a patient's quality of life. The metabolites present in biological systems are expected to be key mediators and the changes in these metabolites play an important role in promoting health. Metabolomics can unravel the global metabolic changes and identify significant biological pathways involved in disease development. However, the role of metabolites in lung cancer is still largely unknown. In the present study, we developed a liquid chromatography coupled with tandem mass spectrometry method for biomarker discovery and identification of non-small cell lung cancer (NSCLC) from metabolomics data sets and aimed to investigate the metabolic profiles of NSCLC samples to identify potential disease biomarkers and to reveal the pathological mechanism. After cell metabolite extraction, the metabolic changes in NSCLC cells were characterized and targeted metabolite analysis was adopted to offer a novel opportunity to probe into the relationship between differentially regulated cell metabolites and NSCLC. Quantitative analysis of key enzymes in the disturbed pathways by proteomics was employed to verify metabolomic pathway changes. A total of 13 specific biomarkers were identified in NSCLC cells related with metabolic disturbance of NSCLC morbidity, which were involved in 4 vital pathways, namely glycine, serine and threonine metabolism, aminoacyl-tRNA biosynthesis, tyrosine metabolism and sphingolipid metabolism. The proteomics analysis illustrated the obvious fluctuation of the expression of the key enzymes in these pathways, including the downregulation of 3-phosphoglycerate dehydrogenase, phosphoserine phosphatase, tyrosinase and argininosuccinic acid catenase. NSCLC occurrence is mainly related to amino acid and fatty acid metabolic alteration. These findings highlight that the metabolome can provide information on the molecular profiles of cells, which can aid in investigating the metabolite changes to reveal the pathological mechanism.

The relationship of social support, mental health, and health-related quality of life in human immunodeficiency virus-positive men who have sex with men: From the analysis of canonical correlation and structural equation model: A cross-sectional study.

The objective of this study was to reveal the relationships of mental health, social support, health-related quality of life (HRQOL) as well as their dimensions in HIV-positive men who have sex with men (MSM).HIV-positive MSM were interviewed by a cross-sectional study design using the world Health Organization quality of life bref scale, social support rating scale, and self-rated anxiety and depression scales. Canonical correlation analysis and structural equation model (SEM) were utilized to analyze to the collected data.Three first pair of canonical variables that was statistically significant (P < .0001) and verified could account for the largest cumulative proportion were computed from canonical correlation analysis. The results showed, among the dimensions, depression and anxiety were negatively correlated with support utilization and physical health, while subjective support and support utilization were positively correlation with social relationship health. Structural equation model results showed that support utilization (0.632, T = 10.44), depression (0.816, T = 20.37), and environmental dimension (0.833, T = 38.47) had the largest standardized factor loading in social support, mental health, and HRQOL. The structural coefficient between social support and mental health was -0.433 (T = -5.88), between mental health and HRQOL was -0.592 (T = -10.33), between social support and HRQOL was 0.290 (T = 4.10), indicated social support not only exerted a direct influence, but also mediated mental health to have an indirect effect on HRQOL for HIV-positive MSM.Environmental dimension is the foremost factor of HRQOL for HIV-positive MSM. Alleviating anxiety symptoms maybe improve physical health, while promoting the support utilization is an effective measure of alleviating depression and improving social relationship health for this special group.

Identification of a Novel HIV-1 Unique Recombinant Form Comprising CRF01_AE, Subtype B', and CRF65_cpx Among Men Who Have Sex with Men in Jilin, China.

The current HIV-1 epidemic in China is featured by diverse subtypes and continual emergence of new recombinant viruses. This study identified a novel unique recombinant form (URF), JL16013, among men who have sex with men (MSM) in Jilin, China. The JL16013 virus was different from all known subtypes and set up a distinct branch on the phylogenetic tree. This virus had a CRF01_AE backbone with two subtype B' fragments and one CRF65_cpx fragment inserted into gag, pol, env, and nef regions, suggesting that this novel URF might have originated from the CRF01_AE, subtype B', and CRF65_cpx viruses that were cocirculating in Jilin province. This was the first report of the CRF01_AE/B'/CRF65_cpx recombinant in China. Identification of this URF indicated the severity and complexity of the HIV-1 epidemic among MSM in Jilin province. Timely surveillance of new HIV-1 infections and new recombinants among the MSM population is urgently required.

PTK6 promotes hepatocellular carcinoma cell proliferation and invasion.

Protein tyrosine kinase 6 (PTK6) is a nonreceptor tyrosine kinase that plays a crucial role in some tumors. However, the role of PTK6 is still unknown in hepatocellular carcinoma (HCC). In this study, we demonstrated that the PTK6 expression was upregulated in HCC tissues compared with adjacent normal tissues. Moreover, PTK6 was upregulated in the HCC cell lines (Bel7402, Hep3B, SMMC7721 and HepG2) compared with the normal liver epithelial cell line (THLE3). Ectopic expression of PTK6 promoted SMMC7721 cell proliferation, colony formation and invasion. Moreover, inhibition PTK6 expression suppressed the SMMC7721 cell proliferation, colony formation and invasion. Overexpression of PTK6 suppressed ERK1/2 phosphorylated expression. These data suggested that PTK6 played an oncogene role in the development of HCC.

Health-Related Quality of Life in HIV-Infected Men Who Have Sex with Men in China: A Cross-Sectional Study.

BACKGROUND China is undergoing a rapid growth in the human immunodeficiency virus (HIV) epidemic involving men who have sex with men (MSM). Reports about their health-related quality of life (HRQOL) are scarce. This study aimed to assess the HRQOL and factors influencing HIV-positive MSM in a city in the northeast of China. MATERIAL AND METHODS A cross-sectional study was conducted in Harbin city (Heilongjiang, China). HIV-positive MSM (n=125) were interviewed using the WHOQOL-HIV-BRIEF scale, the Berger HIV Stigma Scale, and other HIV-related questionnaires from June to August 2013. RESULTS Among the 6 dimensions of the HRQOL, HIV-related stigma was negatively associated with psychological (r=-0.316, P=0.0003) and spirituality domains (r=-0.324, P=0.0002). Physician support was positively associated with independence domain (r=0.393, P<0.0001). Hostile mentality was associated with psychological (r=0.479, P<0.0001) and spirituality domains (r=0.431, P<0.0001). Adverse effects of HAART were significantly correlated with physical (r=-0.542, P<0.0001) and psychological (r=-0.554, P<0.0001) domains. Multiple logistic regression showed that stigma (odds ratio (OR)=1.251, 95% confidence interval (95%CI): 1.088-1.439, P=0.002) and adverse effects of HAART (OR=1.117, 95%CI: 1.069-1.167, P<0.0001) were independent risk factors for low HRQOL. Physician support (OR=0.961, 95%CI: 0.941-0.982, P=0.0002) and CD4+ counts >350 (OR=0.033, 95%CI: 0.005-0.208, P=0.001) were independent protective factors in MSM receiving HAART. Hostile mentality (OR=0.936, 95%CI: 0.906-0.967, P<0.0001) was an independent protective factor of HRQOL in MSM not receiving HAART. CONCLUSIONS Psychological factors such as HIV-related stigma, hostile mentality, and physician support have a significant effect on HRQOL in MSM. These findings suggest specific psychological interventions to improve HRQOL in HIV-positive MSM in China.

miRNA-296-3p modulates chemosensitivity of lung cancer cells by targeting CX3CR1.

Lung cancer is the most common type of cancer-related death in developed countries. MicroRNAs (miRNAs) are small non-coding RNAs, which regulates gene expression in cancer. Recent studies demonstrate that the microRNA-293-3p (miR-293-3p) may play as an oncogene or a tumor suppressor. However, its expression and roles in non-small cell lung cancer (NSCLC) is not known. In this study, our purpose is to investigate the expression and roles of miR-296-3p in NSCLC. The findings indicated that miR296-3p inhibited NSCLC cell proliferation, enhance the drug resistance, and apoptosis. Data of luciferase reporter assays demonstrated that the CX3CR1 gene was a direct regulator of tumorsuppressive miR296-3p. Moreover, overexpressed CX3CR1 was confirmed in NSCLC clinical specimens. Inhibition of CX3CR1 could inhibit cancer cellular survival and increase chemotherapy sensitivity. There was a negative relationship between miR296-3p and CX3CR1 expression in NSCLC tissues. Our study elucidates that miR296-3p plays a suppressive role in NSCLC by inhibiting CX3CR1 expression.

Does short preoperative statin therapy prevent infectious complications in adults undergoing cardiac or non-cardiac surgery? A meta-analysis of 5 randomized placebo-controlled trials.

OBJECTIVES: To evaluate the effect of preoperative statin therapy on the incidence of postoperative infection.  METHODS: This systematic review of the literature was carried out in August 2015. Studies were retrieved via PubMed, Embase, and the Cochrane Library (1980 to 2015), and the reference files were limited to English-language articles. We used a standardized protocol, and a meta-analysis was performed for data abstraction.  RESULTS: Five studies comprising 1,362 patients qualified for the analysis. The incidence of postoperative infections in the statin group (1.1%) was not significantly lower than that in the placebo group (2.4%), with a risk ratio (RR) of 0.56 (95% confidence interval [CI] 0.24-1.33, p=0.19). Patients of 3 studies underwent cardiac surgery. The aggregated results of these studies failed to show significant differences in postoperative infection when a fixed effects model was used (RR: 0.39; 95% CI: 0.08-1.97, p=0.26].   CONCLUSIONS: We failed to find sufficient evidence to support the association between statin use and postoperative infectious complications. The absence of any evidence for a beneficial effect in available randomized trials reduces the likelihood of a causal effect as reported in observational studies.