The effect of statin therapy in combination with ezetimibe on circulating C-reactive protein levels: a systematic review and meta-analysis of randomized controlled trials

Background

Previous studies have reported that statin or ezetimibe therapy has an anti-inflammatory effect. However, the results of individual studies on the effect of statin therapy in combination with ezetimibe on C-reactive protein (CRP) and high-sensitivity CRP (hs-CRP) levels have not been clear. Therefore, the present systematic review and meta-analysis were conducted on randomized clinical trials (RCTs) to evaluate the effect of statin therapy in combination with ezetimibe on CRP and hs-CRP levels.

Methods

A literature search was carried out on the MEDLINE, SciVerse Scopus, and Clarivate Analytics Web of Science databases up to February 2022 to find eligible studies. The pooled effect sizes were considered for weighted mean difference (WMD) and 95% confidence intervals (CI) for CRP and hs-CRP, and it was also determined as standardized weighted mean difference (SMD) for overall CRP. For all variables, a random-effects model was used.

Results

Of the 57 studies included in the systematic review, 53 were used for meta-analysis. Statin therapy in combination with ezetimibe significantly reduced the serum levels of hs-CRP (WMD ??0.2 mg/l; 95% CI ??0.4, ??0.1, P???0.001) and overall CRP (SMD ??0.16 mg/l; 95% CI ??0.2, ??0.07, P???0.001). Nevertheless, CRP levels were not significantly changed by combination therapy. A significant association was observed between the serum low-density lipoprotein cholesterol (LDL-C) changes and hs-CRP levels, which can justify the source of heterogeneity.

Conclusions

The current study showed that statin therapy in combination with ezetimibe could be effective in reducing the levels of hs-CRP and overall CRP.

Graphical abstract

     

Induction of specific cell‐mediated immune responses and protection in BALB/c mice by vaccination with outer membrane vesicles from a Brucella melitensis human isolate

Brucellosis is a worldwide bacterial zoonosis caused by Brucella spp. No approved vaccine is available for human use against the disease. In this study, outer membrane vesicles (OMVs) from a Brucella melitensis biovar 1 human isolate obtained in Iran were used to immunize BALB/c mice (n = 12) by 2 intramuscular injections with a 2‐week interval. Another group of 12 mice was used as non‐vaccinated controls. Two weeks after the last vaccination, six mice of each group were sacrificed, and proliferation and interferon gamma (IFNγ) production responses of their splenocytes were evaluated following in vitro stimulation with killed Brucella cells. The other mice were challenged with the virulent B. melitensis isolate. Two weeks later, mice were killed and spleens were cultured to determine the number of the challenge strain. The results showed proliferative response and IFNγ production of splenocytes from vaccinated mice (stimulation index: 2.18 ± 0.57, and 1519.35 ± 10.70 pg/mL, respectively) were significantly higher than those of control mice (stimulation index: 1.02 ± 0.02, and 210.01 ± 17.58 pg/mL, respectively). Numbers of the challenge strain in spleens of vaccinated mice were also significantly less than those in the controls with 1.6 units of protection. Our study revealed vaccination with OMVs of the B. melitensis isolate could induce specific immune responses and protection against infection in the mouse model suggesting their potential application for active immunization against brucellosis.     

Superior efficacy of co-targeting GFI1/KDM1A and BRD4 against AML and post-MPN secondary AML cells

There is an unmet need to overcome nongenetic therapy-resistance to improve outcomes in AML, especially post-myeloproliferative neoplasm (MPN) secondary (s) AML. Studies presented describe effects of genetic knockout, degradation or small molecule targeted-inhibition of GFI1/LSD1 on active enhancers, altering gene-expressions and inducing differentiation and lethality in AML and (MPN) sAML cells. A protein domain-focused CRISPR screen in LSD1 (KDM1A) inhibitor (i) treated AML cells, identified BRD4, MOZ, HDAC3 and DOT1L among the codependencies. Our findings demonstrate that co-targeting LSD1 and one of these co-dependencies exerted synergistic in vitro lethality in AML and post-MPN sAML cells. Co-treatment with LSD1i and the JAKi ruxolitinib was also synergistically lethal against post-MPN sAML cells. LSD1i pre-treatment induced GFI1, PU.1 and CEBPα but depleted c-Myc, overcoming nongenetic resistance to ruxolitinib, or to BETi in post-MPN sAML cells. Co-treatment with LSD1i and BETi or ruxolitinib exerted superior in vivo efficacy against post-MPN sAML cells. These findings highlight LSD1i-based combinations that merit testing for clinical efficacy, especially to overcome nongenetic therapy-resistance in AML and post-MPN sAML.Subject terms: Acute myeloid leukaemia, Targeted therapies     

Effect of hydroxychloroquine on treatment and recurrence of acute brucellosis: a single-blind,randomized clinical trial

Brucellosis is associated with a high recurrence rate and requires more than one course of standard treatment; therefore, more research is required to find more effective treatments that lead to prompt recovery, and reduce the relapse of disease. This single-blind, randomized study was designed to evaluate the effect of the standard treatment for brucellosis in combination with hydroxychloroquine.A total of 177 patients with acute brucellosis were randomly assigned to one of two treatment groups: doxycycline-streptomycin (DS) and doxycycline-streptomycin-hydroxychloroquine (DSH). Clinical symptoms and signs, serological tests, and side effects of therapy were compared between the two groups during the treatment course and at three and six months after the end of drug therapy. Of the 177 patients, with a mean age of 40.5?±?16.9 years, 66.1% were males. The mean duration of clinical signs prior to admission was 43.4?±?41.1 days. Appropriate clinical responses, relapse, treatment failure, and adverse drug reactions were seen in 98.9%, 1.2%, 0.0%, and 12.6% of patients, respectively, in the DSH group vs. 86.7%, 11.6%, 2.3%, and 19.8% of patients, respectively, in the DS group. There were significant differences in clinical response and relapse rates between the two groups. The addition of hydroxychloroquine to a doxycycline-streptomycin regimen appears to increase the efficacy of treatment, accelerate improvement of clinical symptoms, and significantly reduce the rate of relapse of brucellosis.     

The effects of loading time on osseointegration and new bone formation around dental implants: a histologic and histomorphometric study in dogs

BACKGROUND: Immediate loading of dental implants has been introduced as a method of reducing implant treatment time without compromising its prognosis. In this research, the effects of loading time on the amount of bone-to-implant contact and bone formation around dental implants were evaluated histologically. METHODS: Three months prior to implantation, the lower premolar teeth of 15 dogs were extracted. Three or four dental implants were placed in the healed extraction sites for each dog (N = 48). Dividing the dogs into three groups, the implants were either loaded 48 hours or 1 week later with metallic or prefabricated acrylic crowns or were left unloaded until the time of sacrifice. Three months after implant insertion, the animals were sacrificed and samples were investigated to define the amount of bone-to-implant contact, lamellar and woven bone percentage, and local inflammation of the newly formed bone. RESULTS: No significant difference in the observed criteria was reported among the three groups (P >0.05); however, the unloaded group had the highest degree of bone-to-implant contact and the group loaded 48 hours after the primary implant insertion had the least. The prosthesis type had no significant effect on the implant success rate (P >0.05). The lamellar and woven bone percentage of newly formed bone also did not differ in the three groups (P >0.05). One implant from each group failed in this study. CONCLUSION: Loading time does not seem to significantly affect the degree of osseointegration and bone-to-implant contact and the composition of newly formed bone around dental implants.     

Comparative assessment of the sealing ability of Nd:YAG laser versus a new desensitizing agent in human dentinal tubules: a pilot study

Dentinal hypersensitivity is a painful condition that occurs following periodontal treatment. Many treatment alternatives have been considered for this problem, including treatments with laser and dentinal adhesives. This study compared the sealing ability of Nd:YAG laser versus a new resin in scanning electron microscopy (SEM) micrographs. Ten human premolars were sectioned yielding 30 specimens of each premolar, which were randomly divided into three groups. The laser group was irradiated by Nd:YAG laser (1 W, 10 Hz, 60 s), the resin group was treated with the new Seal & Protect resin according to the manufacturer’s instructions, and the third group served as the control group and did not receive any interventions. After preparation and gold coating of the samples, they were photographed by SEM at two magnifications (1500× and 4000×). The number and diameter (μm) of the dentinal tubules were recorded in selected fields, and analysis of variance (ANOVA) and Tukey tests were used to determine significant differences between groups. The ANOVA results revealed significant differences in both the mean number (P < 0.001) and diameter (P < 0.05) among the three groups. Further statistical analysis showed a significant difference between the laser group and the resin group in both outcome measures (P < 0.05). Thus, both Nd:YAG laser and the new resin reduced the number and diameter of open dentinal tubules, a result that also explains the desensitization mechanism of these interventions. We further conclude that application of the new resin is more effective than Nd:YAG laser in minimizing the number and diameter of exposed dentinal tubules.