Progress in the development of Modulators targeting Frizzleds.

The Frizzleds (FZDs) receptors on the cell surface belong to the class F of G protein-coupled receptors (GPCRs) which are the major receptors of WNT protein that mediates the classical WNT signaling pathway and other non-classical pathways. Besides, the FZDs also play a core role in tissue regeneration and tumor occurrence. With the structure and mechanism of FZDs activation becoming clearer, a series of FZDs modulators (inhibitors and agonists) have been developed, with the hope of bringing benefits to the treatment of cancer and degenerative diseases. Most of the FZDs inhibitors (small molecules, antibodies or designed protein inhibitors) block WNT signaling through binding to the cysteine-rich domain (CRD) of FZDs. Several small molecules impede FZDs activation by targeting to the third intracellular domain or the transmembrane domain of FZDs. However, three small molecules (FZM1.8, SAG1.3 and purmorphamine) activate the FZDs through direct interaction with the transmembrane domain. Another type of FZDs agonists are bivalent or tetravalent antibodies which activate the WNT signaling via inducing FZD-LRP5/6 heterodimerization. In this article, we reviewed the FZDs modulators reported in recent years, summarized the critical molecules' discovery processes and the elucidated relevant structural and pharmacological mechanisms. We believe the summaried molecular mechanisms of the relevant modulators could provide important guidance and reference for the future development of FZD modulators.

Insights into vaccines for elderly individuals: from the impacts of immunosenescence to delivery strategies.

Immunosenescence increases the risk and severity of diseases in elderly individuals and leads to impaired vaccine-induced immunity. With aging of the global population and the emerging risk of epidemics, developing adjuvants and vaccines for elderly individuals to improve their immune protection is pivotal for healthy aging worldwide. Deepening our understanding of the role of immunosenescence in vaccine efficacy could accelerate research focused on optimizing vaccine delivery for elderly individuals. In this review, we analyzed the characteristics of immunosenescence at the cellular and molecular levels. Strategies to improve vaccination potency in elderly individuals are summarized, including increasing the antigen dose, preparing multivalent antigen vaccines, adding appropriate adjuvants, inhibiting chronic inflammation, and inhibiting immunosenescence. We hope that this review can provide a review of new findings with regards to the impacts of immunosenescence on vaccine-mediated protection and inspire the development of individualized vaccines for elderly individuals.

Association of NUDT15 gene polymorphism with adverse reaction, treatment efficacy, and dose of 6-mercaptopurine in patients with acute lymphoblastic leukemia: a systematic review and meta-analysis.

6-mercaptopurine (6-MP) serves as the backbone in the maintenance regimens of acute lymphoblastic leukemia (ALL). We aimed to evaluate the influence of NUDT15 gene polymorphism on the risk of myelosupression, hepatotoxicity and interruption of 6-MP, as well as treatment efficacy and dose of 6-MP in ALL patients. A total of 24 studies with 3,374 patients were included in this meta-analysis. We found 9-fold higher risk of 6-MP induced leukopenia (odds ratio [OR] =9.00, 95% confidence interval [CI]: 3.73-21.74) and 2.5-fold higher risk of 6-MP-induced neutropenia (OR=2.52, 95% CI: 1.72-3.69) for NUDT15 c.415C>T variant carriers in the dominant model. Moreover, we found that the dose intensity of 6-MP in ALL patients with one NUDT15 c.415C>T variant alleles (CT) was 19% less than that in wild-type patients (CC) (mean differences: 19.43%, 95% CI: -25.36 to -13.51). The tolerable dose intensity of 6-MP in NUDT15 c.415C>T homozygote variant (TT) and heterozygote variant (CT) carriers was 49% and 15% less than that in wild-type patients, respectively. The NUDT15 c.415C>T variant group (CT+TT) had seven times (OR=6.98, 95% CI: 2.83-17.22) higher risk of developing 6-MP intolerance than the CC group. However, NUDT15 c.415C>T polymorphism did not appear significantly associated with hepatotoxicity, treatment interruption or relapse incidence. We concluded that NUDT15 c.415C>T was a good predictor for 6-MP-induced myelosuppression in ALL patients. The dose intensity of 6-MP in ALL patients with NUDT15 c.415C>T variants was significantly lower than that in wild-type patients. This research provided a basis for further investigation into relations between NUDT15 gene and adverse reaction, treatment efficacy and dose intensity of 6-MP.

Construction of silver-coated high translucent zirconia implanting abutment material and its property of antibacterial.

High translucent zirconia (HTZ) has excellent mechanical properties, biocompatibility, and good semi-translucency making it an ideal material for aesthetic anterior dental implant abutments without antibacterial properties. In the oral environment, the surface of the abutment material is susceptible to microbial adhesion and biofilm formation, which can lead to infection or peri-implantitis and even implant failure. This study aims to promote the formation of a biological seal at the implant-soft tissue interface by modifying the HTZ surface, using the load-bearing capacity of the aluminosilicate porous structure and the broad-spectrum antibacterial effect of silver nanoparticles to prevent peri-implant bacterial infection and inflammation and to improve the success rate and prolong the use of the implant. FE-SEM (field emission scanning electron microscopes), EDS (energy dispersive spectroscopy), and XPS (X-ray photoelectron spectroscopy) results showed that aluminosilicate non-vacuum sintering can form open micro- and nanoporous structures on HTZ surfaces, and that porous aluminosilicate coatings obtain a larger number, smaller size, and more uniformly shaped silver nanoparticles than smooth aluminosilicate coatings, and could be deposited deeper in the coating. The ICP-AES (inductively coupled plasma-atomic emission spectroscopy) results showed that the early silver ion release of both the smooth silver coating and the porous silver coating was obvious, the silver ion concentration released by the former was higher than that of the latter. However, the silver ion concentration released by the porous silver coating was higher than that of the smooth coating when the release slowed down. Both smooth and porous silver coatings both inhibited E. coli (Escherichia coli), S. aureus (Staphylococcus aureus), and L. acidophilus (L. acidophilus), and porous silver coatings had stronger antibacterial properties. The silver coating was successfully constructed on the surface of HTZ, through aluminium silicate sintering and silver nitrate solution impregnation. It was found that the high concentration environment of silver nitrate solution was more advantageous for nano-Ag deposition, and the non-vacuum sintered porous surface was able to obtain a larger number of nano-Ag particles with smaller sizes. The porous Ag coating exhibited superior antibacterial properties. It was suggested that the HTZ with silver coating had clinical application, and good antibacterial properties that can improve the survival rate and service life of implants.

Lipopolysaccharide Activating NF-kB Signaling by Regulates HTRA1 Expression in Human Retinal Pigment Epithelial Cells.

Inflammation and elevated expression of high temperature requirement A serine peptidase 1 (HTRA1) are known high risk factors for age-related macular degeneration (AMD). However, the specific mechanism that HTRA1 causes AMD and the relationship between HTRA1 and inflammation remains unclear. We found that lipopolysaccharide (LPS) induced inflammation enhanced the expression of HTRA1, NF-κB, and p-p65 in ARPE-19 cells. Overexpression of HTRA1 up-regulated NF-κB expression, and on the other hand knockdown of HTRA1 down-regulated the expression of NF-κB. Moreover, NF-κB siRNA has no significant effect on the expression of HTRA1, suggesting HTRA1 works upstream of NF-κB. These results demonstrated that HTRA1 plays a pivotal role in inflammation, explaining possible mechanism of overexpressed HTRA1-induced AMD. Celastrol, a very common anti-inflammatory and antioxidant drug, was found to suppress inflammation by inhibiting phosphorylation of p65 protein efficaciously in RPE cells, which may be applied to the therapy of age-related macular degeneration.

The Efficacy and Safety of Brolucizumab for the Treatment of nAMD: A Systematic Review and Meta-Analysis.

Introduction: As demonstrated in pivotal clinical trials, brolucizumab can be used to treat neovascular age-related macular degeneration (nAMD) because it antagonizes vascular endothelial growth factor (VEGF) in the vitreous. However, brolucizumab may cause retinal vasculitis obliterans in the presence of inflammation in the eyes. In the present study, a meta-analysis of randomized controlled trials (RCTs) was conducted to evaluate the efficacy and safety of brolucizumab. Methods: ClinicTrail.gov., Embase, Cochrane Library, and PubMed were retrieved from inception until 31 December 2021 for RCTs assessing the efficacy and safety of brolucizumab. Changes in best corrected visual acuity (BCVA) and central sub-field thickness (CSFT) and incidence of adverse events, serious adverse events, and serious ocular adverse events were extracted from eligible RCTs. A meta-analysis was performed using RevMan 5.4.1. Results: A total of six RCTs with 3,574 participants were finally involved in this meta-analysis. The changes of best corrected visual acuity (BCVA) showed no statistically significant difference between the brolucizumab-treated group and aflibercept-treated group. Brolucizumab induced higher central sub-field thickness (CSFT) reduction than the control agent (aflibercept). The incidence of adverse events was similar between the brolucizumab group and control group (OR 0.63, 95% CI 0.37 to 1.08, p = 0.09), and brolucizumab caused fewer serious adverse events (OR 0.78, 95% CI 0.63 to 0.95, p = 0.01). However, brolucizumab could lead to more serious ocular adverse events than Lucentis and aflibercept (OR 2.15, 95% CI 1.11 to 4.16, p = 0.02). Conclusion: Brolucizumab was non-inferior to other anti-VEGF agents in improving BCVA and decreasing CSFT. But it caused more serious ocular adverse events which is worthy of special attention by ophthalmologists.

Safe and Effective Treatment for Anemic Patients With Chronic Kidney Disease: An Updated Systematic Review and Meta-Analysis on Roxadustat.

Background: Roxadustat is a new oral drug for anemia in chronic kidney disease (CKD). This study aimed to synthesize the evidence from randomized controlled trial (RCT)-based studies that estimated the efficacy and safety of roxadustat in anemia patients with non-dialysis-dependent (NDD) and dialysis-dependent (DD) CKD. Methods: We searched the PubMed, Web of Science, and Cochrane Central Register of Controlled Trials (CENTRAL) databases for related published studies. Moreover, we manually searched relevant pharmaceutical company websites and two international clinical trial registers to search for published and unpublished RCTs comparing roxadustat with erythropoietin-stimulating agents (ESAs) or placebo. Results: Fifteen RCTs (seven for DD-CKD patients, eight for NDD-CKD patients) were included in the meta-analysis, with 10,189 patients, 4,810 DD-CKD patients, and 5,379 NDD-CKD patients enrolled. Compared with ESAs (epoetin alfa or darbepoetin alfa) and placebo, roxadustat raised the hemoglobin level [weighted mean difference (WMD): 0.82 g/dL; 95% confidence interval (CI): 0.43-1.21], transferrin level (WMD: 0.5 g/L; 95% CI: 0.34-0.65), and TIBC level (WMD: 41.79 µg/dL; 95% CI: 38.67-44.92) and lowered the hepcidin level (WMD: -37.38 ng/ml; 95% CI: -46.63- -28.12) in both the DD-CKD and NDD-CKD patients with renal anemia. Roxadustat improved hemoglobin response and lowered the ferritin and TAST levels in the NDD-CKD patients but not in the DD-CKD patients. Furthermore, there was no difference between the treatment-emergent adverse events (TEAEs) of roxadustat and that of ESAs or placebo. But the incidence of serious TEAEs in the roxadustat group was significantly higher with NDD-CKD patients (OR: 1.15; 95% CI: 1.02-1.29). Conclusion: This study confirmed that roxadustat therapy could alleviate the anemia of DD-CKD and NDD-CKD patients by raising the hemoglobin level and regulating iron metabolism, but increased serious incidences of treatment-emergent adverse events (TEAEs) in NDD-CKD patients.

Diagnosis Test Meta-Analysis for Apolipoprotein E in Alzheimer's Disease.

OBJECTIVE: To evaluate the diagnostic value of apolipoprotein E (APOE) gene in Alzheimer's disease (AD). METHODS: Databases including PubMed, EMBASE, Google Scholar, Wanfang Med online, China National Knowledge Infrastructure (CNKI), and China Biomedical Literature Database (CBM) were searched for literatures in English or Chinese. No limitations on the date. The sensitivity, specificity, likelihood ratio, and diagnostic odds ratio were pooled for meta-analysis. The symmetric receiver operator characteristic curve (SROC) and Fagan's Nomogram were drawn, and metaregression and subgroup analysis were used to explore the source of heterogeneity. RESULTS: A total of 13 studies, including 2662 cases and 8843 controls, were analyzed. The combined sensitivity (SEN) was 0.62 (95% CI (0.58-0.66)), specificity (SPE) was 0.84 (95% CI (0.81-0.86)), the positive likelihood ratio was 3.8 (95% CI (3.3-4.3)), and the negative likelihood ratio was 0.45 (95% CI (0.41-0.49)). The area under the ROC curve was 0.80, and the diagnostic ratio (DOR) was 8. Neither publication bias was detected in Deeks' funnel plot, nor threshold effect was shown in the SROC. Metaregression analysis showed that the diagnostic methods, experimental design, and sample size contributed to the heterogeneity in SEN, while the diagnostic methods, experimental design, blind evaluation on test results, and sample size contributed to the heterogeneity in SPE. When the pretest probability was set as 50%, the posterior probability in Fagan's Nomogram was 79%, the positive likelihood ratio (LRP) was 5, and the negative likelihood ratio (LRN) was 0.42. CONCLUSIONS: AD could neither be confirmed nor excluded by the APOE genotype test. The sensitivity and specificity of the APOE gene test were relatively low in the diagnosis of AD. The diagnostic value of APOE ε4 gene in AD was moderate; it might play an important role in the prevention of AD.

A modified method for preparation of fluorescent MantGDP bound CDC42.

Small GTPase cycled between the GDP-bound inactive state and GTP-bound active state, catalyzed by guanine nucleotide exchange factors (GEFs). Guanine nucleotide exchange assay was a direct way to investigate the specificity, activity, and kinetics of GEFs. The N-methylanthraniloyl derivative of GDP (mantGDP), which was bound to small GTPase, served as a substitution for labeled small GTPase involved in bioluminescent, colorimetric, or radioactive methods due to its safety and sensitivity. In this study, we present an economical and efficient approach to prepare qualified mantGDP-bound CDC42, a member of the Rho GTPase family. In our protocol, with a Kd value of 0.048 µM, alkaline phosphatase hydrolysis of CDC42 increased mantGDP binding affinity to CDC42, allowing mant-nucleotide associating onto CDC42 more easily. Only 1.5-fold molar excess of mantGDP was required to prepare mantGDP-bound CDC42 without nonhydrolyzable GTP analog and high performance liquid chromatography. The mantGDP-bound CDC42 was verified to be efficient for measuring the guanine nucleotide exchange activity of VAV2.

Characterization of guanine nucleotide exchange activity of DH domain of human FGD2.

FGD2, a member of FGD family, contains a Dbl homology domain (DH) and two pleckstrin homology domains segregated by a FYVE domain. The DH domain has been deduced to be responsible for guanine nucleotide exchange of CDC42 to activate downstream factors. Our aim was to build a prokaryotic expression system for the DH domain and to examine its guanine nucleotide exchange activity toward CDC42 in vitro. A recombinant vector, which was successfully constructed based on pGEX-6P-1, was employed to express the DH domain of human FGD2 (FGD2-DH) in E. coli BL21 (DE3). Purified FGD2-DH behaved as a homogeneous monomer with an estimated molecular weight that corresponded to the theoretical molecular weight and was predicted to be an α-helix protein by circular dichroism spectroscopy. FGD2-DH displayed weak guanine nucleotide exchange activity in vitro and very weak interactions with CDC42 following glutaraldehyde cross-linking.

The association of the PCSK9 rs562556 polymorphism with serum lipids level: a meta-analysis.

BACKGROUND: Studies had investigated the associations between proprotein convertase subtilisin/kexin type 9 SNP rs562556 and serum lipids levels and response to statin treatment, however, the results remained inconclusive. We conducted this meta-analysis to elucidate the relationship of rs562556 and serum lipids levels. METHODS: All eligible studies met the inclusion criteria were retrieved from multiple databases. Relative data were extracted from each study. Review Manager (version 5.3.5) and STATA 12.0 software was used to perform this meta-analysis. Pooled standardized mean difference (SMD) with 95% CI was employed to evaluate the association of rs562556 with serum lipids levels. RESULTS: A total of 7 eligible articles involving 4742 subjects were included in the final meta-analysis. The results revealed that the G carriers had lower levels of total cholesterol (SMD: 0.14, 95% Cl: 0.06-0.23, P = 0.001) and LDL-C(SMD: 0.13, 95% Cl: -0.55-0.22,P = 0.002) than the non-carriers. The statistical results also illustrated that the G carriers had lower relative risk (SMD: 1.38, 95% Cl: 1.02-1.85, P = 0.003) than the non-carriers. CONCLUSIONS: The results of the current meta-analysis for the first time indicated the relevance of rs562556 and lower serum cholesterol levels.

Protective effect of ethyl vanillin against Aß-induced neurotoxicity in PC12 cells via the reduction of oxidative stress and apoptosis.

Increased aggregation of ß-amyloid (Aß) peptides induces oxidative stress, which is considered a major contributor in the development of Alzheimer's disease (AD). Prevention of Aß-induced neurotoxicity is proposed as a possible modality for treatment of AD. The present study aimed to elucidate possible effects of ethyl vanillin (EVA), an analog of vanillin isolated from vanilla beans, on the Aß1-42-induced oxidative injury in PC12 cells. EVA restrained the decrease in PC12 cell viability and apoptosis induction caused by treatment with Aß1-42. In addition, EVA markedly alleviated intracellular lipid peroxidation as demonstrated by malondialdehyde levels and reactive oxygen species production in Aß1-42-treated PC12 cells. In addition, the reduction in the activity levels of the antioxidative enzymes superoxide dismutase, catalase and glutathione peroxidase was detected in Aß1-42-treated PC12 cells. This effect was partially reversed by treatment with EVA. Furthermore, the results indicated that EVA attenuated Aß1-42-induced caspase-3 activation and the increase noted in the apoptosis regulator Bcl-2/apoptosis regulator Bax ratio of PC12 cells. These results indicated that EVA could be used as an efficient and novel agent for the prevention of neurodegenerative diseases via inhibition of oxidative stress and cell apoptosis.

The association between maternal methylenetetrahydrofolate reductase C677T and A1298C polymorphism and birth defects and adverse pregnancy outcomes.

Published studies indicate the MTHFR C677T and A1298C polymorphisms are associated with abnormal homocysteine levels, which may cause various pregnancy complications and birth defects. However, the results obtained from different studies have been inconsistent. Therefore, this meta-analysis explores the association between MTHFR polymorphisms and birth defects and adverse pregnancy outcomes. The PubMed, ScienceDirect, Embase, and China Biology Medicine literature databases and ClinicalTrials were searched. Analyses of public bias, meta-regression, subgroups, and sensitivity were used to ensure the robustness of our results. MTHFR C677T was significantly associated with recurrent pregnancy loss in developing countries (odds ratio [OR], 1.34; 95% confidence interval [CI], 1.20-1.50) but not in developed countries (OR, 0.87; 95% CI, 0.68-1.11). No significant relationship was found between MTHFR A1298C and recurrent pregnancy loss (OR, 1.04; 95% CI, 0.93-1.18). MTHFR C677T and A1298C were not associated with preeclampsia (OR, 1.06; 95% CI, 0.97-1.16 and OR, 1.16; 95% CI, 0.97-1.39, respectively), and C677T was not associated with placental abruption (OR, 1.03; 95% CI, 0.87-1.21), intrauterine growth retardation (OR, 1.02; 95% CI, 0.90-1.15), or congenital heart disease (OR, 1.05; 95% CI, 0.89-1.25). MTHFR C677T, but not A1298C, was associated with neural tube defects (OR, 1.24; 95% CI, 1.08-1.42) and Down syndrome (OR, 1.65; 95% CI, 1.39-1.95). CONCLUSION: Although MTHFR C677T and A1298C are significantly associated with some types of congenital defects and adverse pregnancy outcomes, the impact of these polymorphisms is moderate.

Relevance of methylenetetrahydrofolate reductase gene variants C677T and A1298C with response to fluoropyrimidine-based chemotherapy in colorectal cancer: a systematic review and meta-analysis.

Methylenetetrahydrofolate reductase (MTHFR) is a critical enzyme influencing the metabolism of fluoropyrimidines. The relevance of MTHFR polymorphisms with the clinical response to fluoropyrimidine-based chemotherapy has been explored, but the results remain controversial. Thus, a meta-analysis was performed to provide a comprehensive estimate in this account. Relevant studies were identified through PubMed, Embase and Web of Science databases from inception up to May 2017. Odds ratios (ORs) with corresponding 95% confidence intervals (CIs) were applied to assess the strength of association. A total of 2118 colorectal cancer patients from 21 studies were included in the meta-analysis. Overall, there was no significant association between MTHFR C677T (rs1801133) or A1298C (rs1801131) polymorphisms and the clinical response to fluoropyrimidine-based chemotherapy under all of the three genetic models (allele model, dominant model, and recessive model) and stratification analysis, except for the retrospective study subgroup in the dominant model of MTHFR C677T and the "5-Fu + FA" treatment group in the allele contrast of MTHFR A1298C. No or moderate heterogeneity was observed in all genetic models. This meta-analysis suggested that MTHFR polymorphisms could not be considered as reliable factors for predicting the clinical response to fluoropyrimidine-based chemotherapy in colorectal cancer patients.

Shikonin Protects PC12 Cells Against ß-amyloid Peptide-Induced Cell Injury Through Antioxidant and Antiapoptotic Activities.

Excessive accumulation of ß-amyloid (Aß) is thought to be a major causative factor in the pathogenesis of Alzheimer's disease (AD). Pretreating Aß-induced neurotoxicity is a potential therapeutic approach to ameliorate the progression and development of AD. The present study aimed to investigate the neuroprotective effect of shikonin, a naphthoquinone pigment isolated from the roots of the traditional Chinese herb Lithospermum erythrorhizon, on Aß1-42-treated neurotoxicity in PC12 cells. Pretreating cells with shikonin strongly improved cell viability, decreased the malondialdehyde and reactive oxygen species (ROS) content, and stabilized the mitochondrial membrane potential in Aß1-42-induced PC12 cells. In addition, shikonin strongly improved the response of the antioxidant system to ROS by increasing the levels of superoxidedismutase, catalase and glutathione peroxidase. Furthermore, shikonin has the ability to reduce proapoptotic signaling by reducing the activity of caspase-3 and moderating the ratio of Bcl-2/Bax. These observations indicate that shikonin holds great potential for neuroprotection via inhibition of oxidative stress and cell apoptosis.

The protective effect of shikonin on renal tubular epithelial cell injury induced by high glucose.

Hyperglycemia-induced oxidative stress is thought to play a critical role in the pathogenesis of diabetic nephropathy (DN). Treating high-glucose (HG)-induced proximal tubule injury has become a patential therapeutic option to attenuate the onset and progression of DN. The present study aimed to investigate the renoprotective effect of shikonin, the chief active compound extracted from the roots of the traditional Chinese herb Lithospermum erythrorhizon, on HG-induced cytotoxicity in NRK-52E cells. Treating cells with HG significantly reduce cell viability while also significantly increasing content of reactive oxygen species (ROS). Treating the cells with shikonin improved these changes induced by HG. Shikonin strongly stabilized mitochondrial membrane potential in HG-induced NRK-52E cells. In addition, treatment with shikonin upregulated antioxidant system in response to ROS by increasing levels of SOD and CAT. Furthermore, shikonin also strongly decreased the levels of activated caspase-3, Bax and p-GSK-3ß while increased the p-AKT level. These findings provide that the renoprotective effects of shikonin against HG-induced cytotoxicity in NRK-52E cells may be mediated in inhibiting oxidative stress through activating of the AKT signalling pathway.

Influence of Restorative Materials on Color of Implant-Supported Single Crowns in Esthetic Zone: A Spectrophotometric Evaluation.

Restorations of 98 implant-supported single crowns in anterior maxillary area were divided into 5 groups: zirconia abutment, titanium abutment, and gold/gold hue abutment with zirconia coping, respectively, and titanium abutment with metal coping as well as gold/gold hue abutment with metal coping. A reflectance spectrophotometer was used to evaluate the color difference between the implant crowns and contralateral/neighboring teeth, as well as the color difference between the peri-implant soft tissue and the natural marginal mucosa. The mucosal discoloration score was used for subjective evaluation of the esthetic outcome of soft tissue around implant-supported single crowns in the anterior zone, and the crown color match score was used for subjective evaluation of the esthetic outcome of implant-supported restoration. ANOVA analysis was used to compare the differences among groups and Spearman correlation was used to test the relationships. A gold/gold hue abutment with zirconia coping was the best choice for an esthetic crown and the all-ceramic combination was the best for peri-implant soft tissue. Significant correlation was found between the spectrophotometric color difference of peri-implant soft tissue and mucosal discoloration score, while no significant correlation was found between the total spectrophotometric color difference of implant crown and crown color match score.

Systematic Review and Meta-Analysis of the Efficacy and Safety of Telavancin for Treatment of Infectious Disease: Are We Clearer?

Objective: Telavancin is approved to treat complicated skin and skin structure infections, hospital-acquired, and ventilator-associated bacterial pneumonia caused by Staphylococcus aureus. A previous meta-analysis of randomized controlled trials suggested that it might be an alternative to vancomycin in cases of difficult-to-treat meticillin-resistant S. aureus infections. We did a meta-analysis including one new trial to access the efficacy and safety of telavancin. Methods: We searched PubMed, Cochrane Central Register of Controlled Trials, EMBASE and ClinicalTrials.gov up to December 30, 2015 to identify randomized controlled trials that assessed the clinical efficacy, eradication efficiency, adverse events and laboratory abnormalities of telavancin vs. other antibiotic agents for bacterial infection. Meta-analysis was performed using Review Manager 5.3.0. Results: Five studies (3790 participants) were included in the meta-analysis. There was no significant difference in treatment success with telavancin than with control antibiotic agents. The pooled pathogen eradication for the telavancin group was numerically higher than that for the control groups, but there was no significant difference. While all-cause mortalities and serious adverse events were comparable between telavancin and control antibiotic agents, adverse event-related withdrawals (OR 1.47, 95% CI 1.13-1.91) were higher in telavancin group. The total number adverse events were more in the telavancin group than in the control groups, especially in the digestive system (OR 1.57, 95% CI 1.37-1.79), nervous system (OR 2.14, 95% CI 1.86-2.47) and urogenital system (OR 2.54, 95% CI 1.99-3.25). Serum creatinine increase (OR 2.25, 95% Cl 1.78-2.85) and hypokalemia (OR 1.74, 95% CI 1.19-2.53) occurred more frequently in telavancin group compared to control groups. Conclusion: Telavancin may be as effective as but no better than the comparison therapy for S. aureus infection. However, because of the high risk of adverse event-related withdrawals and potential nephrotoxicity, prudence with the clinical use of telavancin in infections is required.