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

     

In vitro production of immunoglobulins of various classes and subclasses by cord blood B cells in African neonates: modeling and assessment of determination

Cord blood B cells obtained from neonates of healthy Senegalese mothers were assayed in vitro for their capacity to fully differentiate and secrete immunoglobulins (Ig) of various classes and subclasses. Stimulation of mononuclear cells with SAC particles or anti-micro antibodies in the presence of IL-4, or with IL-2 and IL-10 induced a strong production of IgG, provided that an additional CD40/CD40L signal was present, in contrast to adult cell cultures. Cord blood mononuclear cells differentially stimulated with various cytokines in order to lead to Ig heavy chain switching and production of the various classes/subclasses consistently produced IgG1, IgG3, IgG4, IgE and IgA. This system has been applied to immune cells from African neonates that have not been extensively studied previously. Estimation of Ig production as OD ratios could be applied to cultures where cord blood B cells are stimulated with defined antigens of human pathogens to which the fetus immune system was primed in utero.     

Two polymorphisms in the epithelial cell-derived neutrophil-activating peptide (ENA-78) gene

Increased expression of epithelial cell-derived neutrophil-activating peptide (ENA-78) has been reported in several immune and inflammatory conditions suggesting its role in inflammatory response. We have identified two single nucleotide polymorphisms in the promoter and exon 2 of the ENA-78 gene by scanning the full length gene using DHPLC DNA fragment analysis and DNA sequencing. The polymorphism at position +398 (A/G from the first ATG codon) in exon 2 results in a synonymous substitution not resulting in an amino acid change. The promoter polymorphism was found at position -156 (C/G from the first ATG codon). An assay was designed for the detection of the polymorphisms using SNapshot ddNTP primer extension, followed by capillary electrophoresis (ABI 3100). Allele and genotype frequencies for the promoter -156 polymorphism are presented for 107 healthy Spanish and 54 UK Caucasians. Frequencies for the exon 2 polymorphism are also presented for 63 UK Caucasians.     

Alcohol use,viral hepatitis and liver fibrosis among HIV‐positive persons in West Africa: a cross‐sectional study

Introduction : Liver fibrosis is often the first stage of liver disease in people living with HIV (PLWHIV) in industrialized countries. However, little is known about liver fibrosis and its correlates among PLWHIV in sub‐Saharan Africa. Methods : The study was undertaken in three HIV referral clinics in Côte d’Ivoire, Senegal and Togo. Enrolled PLWHIV underwent a non‐invasive assessment of liver fibrosis combining liver stiffness measure (LSM) with transient elastography and the aspartate aminotransferase‐to‐platelet ratio index (APRI). Significant liver fibrosis was defined as LSM ≥7.1 kPa. Patients were screened for alcohol use (alcohol use disorder identification test (AUDIT)‐C questionnaire), hepatitis B virus (HBV) antigen, hepatitis Delta virus (HDV) antibody and anti‐hepatitis C (HCV) antibody. A logistic regression model was used to identify the factors associated with significant liver fibrosis. Results : A total of 807 PLWHIV were screened at a median age of 43 years (interquartile range (IQR): 36–50). Their median CD4 count was 393 cells/mm³ (IQR: 234–563) and 682 (84.5%) were on antiretroviral therapy (ART). The prevalence of significant fibrosis was 5.3% (3.8–6.7). Infections with HBV and HCV were identified in 74 (9.2%) and nine (1.1%) participants. Main factors associated with liver fibrosis were alcohol use (AUDIT‐C >6): (odds ratio (OR) = 4.0, confidence interval (CI): 1.2–14.0), (Ref. AUDIT‐C <4) and HBV infection (OR = 2.9, CI: 1.2–7.2). Of the 74 patients positively screened for HBV, 50.0% were on a tenofovir‐based ART regimen. Overall, 10% of HIV/HBV coinfected patients were detected with a positive HDV antibody with a higher prevalence in patients with a significant liver fibrosis (43.0%) compared to others (6.3%) (p = 0.01). Conclusions : Considering the WHO recommendations to screen for HBV infection and treat co‐infected patients with tenofovir‐based ART, screening of alcohol use and brief interventions to prevent alcohol abuse should be implemented in West Africa, especially in HBV/HIV co‐infected patients.     

Ophthalmic manifestations of 107 cases with hemolysis, elevated liver enzymes and low platelet count syndrome

OBJECTIVE: To present various ophthalmologic disorders in a clinical series of hemolysis, elevated liver enzymes and low platelet count (HELLP) syndrome cases. METHODS: This is a prospective clinical study performed between 2002 and 2005. One hundred seven HELLP patients attended in either Departments of Ophthalmology or Obstetrics and Gynecology, Medical School, Gaziantep University, Gaziantep, Turkey were evaluated. RESULTS: Mean age was 25.5 (22-36 years). Mean levels were 2.5 gravidity, 1.3 parity, 55,200/mm3 platelet counts, 308.7 U/l aspartate transaminase, 255.4 U/l alanine transaminase, and 1711.6 U/I lactate dehydrogenase. Four patients died (3.7%) despite the proper treatments. Cortical blindness was observed in 3 cases (2.7%), serous retinal detachments in 4 (3.7%), and mild hypertension changes in 18 (16%). CONCLUSION: Ophthalmic complications are possible during and after this syndrome. Almost all ophthalmologic changes recover after delivery by cesarean section, nevertheless, it is essential that ophthalmologists should be aware of retinal disorders when this fatal complication of pregnancy is encountered.     

Malignant melanoma of parotid glands from a neglected lesion: A case report

Observing a metastatic malignant melanoma and its primary lesion at the same time is rare. The histopathological detection of any unusual pigmented lesion is critical.