Comparison of tube shunt implantation and trabeculectomy for glaucoma: a systematic review and meta-analysis.

OBJECTIVE: To compare the efficacy and safety of tube shunt implantation with trabeculectomy in the treatment of patients with glaucoma. METHODS: A systematic literature search was performed for studies comparing tube with trabeculectomy in patients with glaucoma (final search date: 27 February 2022). Comparisons between tube and trabeculectomy were grouped by the type of tube (Ahmed, Baerveldt, Ex-PRESS and XEN). The primary endpoints included intraocular pressure (IOP), IOP reduction (IOPR), IOPR percentage (IOPR%), complete success rate (CSR), qualified success rate (QSR) and adverse events (AEs). RESULTS: Forty-nine studies were included in this meta-analysis and presented data for 3795 eyes (Ahmed: 670, Baerveldt: 561, Ex-PRESS: 473, XEN: 199, trabeculectomy: 1892). Ahmed and Ex-PRESS were similar to trabeculectomy in terms of IOP outcomes and success rate (Ahmed vs trabeculectomy: IOPR%: mean difference (MD)=1.34 (-5.35, 8.02), p=0.69; Ex-PRESS vs trabeculectomy: IOPR%: MD=0.12 (-3.07, 3.31), p=0.94). The IOP outcomes for Baerveldt were worse than those for trabeculectomy (IOPR%: MD=-7.51 (-10.68, -4.35), p<0.00001), but the QSR was higher. No significant difference was shown for the CSR. XEN was worse than trabeculectomy in terms of IOP outcomes (IOPR%: MD=-7.87 (-13.55, -2.18), p=0.007), while the success rate was similar. Ahmed and Ex-PRESS had a lower incidence of AEs than trabeculectomy. Baerveldt had a lower incidence of bleb leakage/wound leakage, hyphaema and hypotonic maculopathy than trabeculectomy but a higher incidence of concurrent cataracts, diplopia/strabismus and tube erosion. The incidence of AEs was similar for the XEN and trabeculectomy procedures. CONCLUSION: Compared with trabeculectomy, both Ahmed and Ex-PRESS appear to be associated with similar ocular hypotensive effects and lower incidences of AEs. However, Baerveldt and XEN cannot achieve sufficient reductions in IOP outcomes similar to those of trabeculectomy. PROSPERO REGISTRATION NUMBER: CRD42021257852.

PARP inhibitor plus chemotherapy versus chemotherapy alone in patients with triple-negative breast cancer: a systematic review and meta-analysis based on randomized controlled trials.

BACKGROUND: Chemotherapy is the standard treatment for triple-negative breast cancer (TNBC). Whether the addition of PARP inhibitors improves treatment efficacy remains controversial clinically. Thus, we performed a meta-analysis to compare the efficacy and safety of combination treatment (PC) and chemotherapy alone (CA). METHODS: Relevant studies were identified through searches of 7 databases. The primary endpoints were progression-free survival (PFS) and overall survival (OS). RESULTS: We screened 317 studies and included seven RCTs involving 2091 patients in the final analysis. PC tended to have better efficacy than CA according to PFS (HR [hazard ratio]: 0.83 [0.75, 0.93], p = 0.001), OS (HR: 0.89 [0.76,1.03], p = 0.11) and overall response rate (ORR) (RR [risk ratio]: 1.19 [0.97,1.46], p = 0.10). However, grade 3-5 AEs (RR: 1.50 [0.87,2.61], p = 0.15) were observed in the PC group. In the PC arm, the 10 most-reported grade 3-5 AEs were neutropenia (62.8%), anemia (28.5%), thrombocytopenia (26.4%), lymphopenia (19.05%), leukopenia (16.9%), fatigue (5%), heart failure (4.76%), lung infection (4.76%), thromboembolic events (4.76%) and ventricular tachycardia (4.76%). Similar results for pathological complete response (pCR), total AEs, rate of complete response (CR), stable disease (SD) and progressive disease (PD), breast conservation rate (BCR), and drug discontinuation (DD) rate were found between the two groups. CONCLUSIONS: For TNBC treatment, the combination of PARP inhibitors and chemotherapy appears to be superior to chemotherapy alone with better antitumor efficacy. However, its higher rate of AEs needs to be taken seriously. More high-quality RCTs are needed to confirm these results.

Preoperative hypoalbuminemia in patients undergoing cardiac surgery: a meta-analysis.

The preoperative serum albumin level has been shown to be associated with adverse postoperative complications, meaning that hypoalbuminemia may also be a risk factor. We performed a meta-analysis to evaluate the association of serum albumin levels with survival and complication rates after cardiac surgery. Relevant articles were identified through seven databases. Twenty studies with 22553 patients (hypoalbuminemia group, n = 9903; normal group, n = 12650) who underwent cardiac surgery met the inclusion criteria after screening. The primary outcomes were that hypoalbuminemia was significantly correlated with serious long-term all-cause mortality (hazard ratio [HR]: 1.95 [1.54-2.48]; P < 0.00001) and increased mortality (risk ratio [RR] = 1.91 [1.61-2.27], P < 0.00001). Hypoalbuminemic patients with cardiopathy were more likely to suffer postoperative complications (bleeding, infections, renal injury, and others) than those whose serum albumin levels were normal. Furthermore, hypoalbuminemia increased the time in the intensive-care unit (ICU) (mean difference [MD] = 1.18 [0.49-1.87], P = 0.0008), length of hospital stay (LOS) (MD = 3.34, 95% CI: 1.88-4.80, P < 0.00001), and cardiopulmonary bypass time (CPB) (MD = 12.40 [1.13-23.66], P = 0.03). Hypoalbuminemia in patients undergoing cardiac surgery appears to have a poor all-cause mortality or increased risk of complications. Adjusted perioperative serum albumin levels and treatment strategies for this high-risk population have the potential to improve the survival.

Effects of preoperative needle biopsy for lung cancer on survival and recurrence: a systematic review and meta-analysis.

Needle biopsy (NB) is used for the diagnosis of lung cancer, but there is still controversy about its effect on the prognosis after surgery. We conducted this meta-analysis to compare the prognosis of lung cancer patients who underwent preoperative NB with that of those who did not. We systematically searched seven databases and Google Scholar for eligible studies. Recurrence-free survival (RFS) and overall survival (OS) were analyzed as primary outcome measures. Nine articles with a collective total of 13,541 patients (NB group, n = 4550; non-NB group, n = 8991) were included in our meta-analysis. OS [hazard ratio (HR) = 1.43 (0.96, 2.12), p = 0.08] and RFS (HR = 1.59 [1.25, 2.01], p = 0.0001) tended to be better in the non-NB group than in the NB group. Pleural recurrence (risk ratio (RR) = 2.40 [1.42, 4.07], p = 0.001) was significantly lower in the non-NB group than in the NB group. The recurrence analysis data did not reach significance, but the overall trend was better for the non-NB group. These findings demonstrate that NB is detrimental to the survival prognosis of lung cancer patients and increases the chance of pleural recurrence.

Efficacy and safety of netarsudil/latanoprost fixed-dose combination vs. monotherapy in open-angle glaucoma or ocular hypertension: A systematic review and meta-analysis of randomized controlled trials.

Objective: As monotherapy is insufficient for some patients, the existing fixed-dose combination (FDC) requires two or more daily administrations with declining adherence. The present study compared the efficacy and safety of netarsudil/latanoprost FDC with monotherapy of its individual components in patients with glaucoma. Methods: A systematic literature search was performed for studies comparing netarsudil/latanoprost fixed-dose combination (FDC) vs. monotherapy in patients with glaucoma. The primary endpoints included intraocular pressure (IOP), intraocular pressure reduction percentage (IOPR%) and adverse events (AEs). Results: Three randomized controlled trial studies (RCTs) involving 1,692 patients (FDC: 556, netarsudil: 577, latanoprost: 559) were included in this meta-analysis. FDC was more effective than netarsudil, with significantly lower diurnal IOP over three time points (8:00 a.m., 10:00 a.m., 4:00 p.m.), mean diurnal IOP (MD = -2.36 [-3.08, -1.63], P < 0.00001) and higher IOPR% (MD = 9.60 [7.86, 11.33], P < 0.00001). When comparing FDC with latanoprost, both mean diurnal IOP (MD = -1.64 [-2.05, -1.23], P < 0.00001) and diurnal IOP across 3 time points were significantly lower with FDC than with latanoprost, while FDC induced significantly higher IOPR% (MD = 6.09 [4.40, 7.77], P < 0.00001). Incidence of total AEs was similar between netarsudil and FDC, but higher with FDC than with latanoprost. Conclusion: Netarsudil/latanoprost FDC appears to be superior to netarsudil or latanoprost alone, with better ocular hypotensive effects. However, there are concerns that netarsudil/latanoprost FDC was associated with a significantly higher incidence of AEs specifically compared with latanoprost. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=311956.

The Effect of Vitamin D Supplementation in Children With Asthma: A Meta-Analysis.

Background: An increasing number of studies have suggested that vitamin D can be used to treat childhood asthma, but its clinical effects are still unclear. We conducted this meta-analysis to examine the latest estimates of the effectiveness and safety of using vitamin D to treat childhood asthma. Methods: The PubMed, The Cochrane Library, ScienceDirect, Embase, Scopus, Ovid MEDLINE, Web of Science, and Google Scholar databases were searched for randomized controlled trials (RCTs) describing vitamin D supplementation interventions for asthmatic children. Asthma exacerbation, vitamin D levels, the predicted percentage of forced expiratory volume in the first second (FEV1%) and adverse effects (AEs) were analyzed as the main outcome measures. Results: After screening, eight RCTs with 738 children were included. Compared with placebos, vitamin D supplementation had a stronger effect on serum vitamin D levels [mean difference (MD) = 13.51 (4.24, 22.79), p = 0.004]. The pooled results indicated that no significant changes were found between the groups in asthma control, as measured by adopting the following indicators: asthma exacerbation [risk ratio (RR) = 0.92 (0.68, 1.25), p = 0.60]; Childhood Asthma Control Test (CACT) scores [MD = 0.15 (-0.43, 0.74), p = 0.61]; hospitalizations for asthma exacerbation [RR = 1.20 (0.48, 2.96), p = 0.70]; acute care visits [RR = 1.13 (0.77, 1.65), p = 0.63]; steroid use [RR = 1.03 (0.41, 2.57), p = 0.95]; and fractional exhaled nitric oxide (FeNO) [MD =-3.95 (-22.87, 14.97), p = 0.68]. However, vitamin D supplementation might reduce the FEV1% [MD = -4.77 (-9.35, -0.19), p = 0.04] and the percentage of predicted forced vital capacity (FVC%) [MD =-5.01 (-9.99, -0.02), p = 0.05] in patients. Subgroup analysis revealed no difference in AEs between the two groups. Conclusions: Vitamin D supplementation significantly increased patients' serum vitamin D levels, but it had no benefit for asthma control. However, vitamin D supplementation might reduce patients' lung function. It is essential to systemically search for more large-scale, rigorous, and well-designed RCTs to fully confirm these conclusions. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021288838, PROSPERO CRD42021288838.

Immune Checkpoint Inhibitors Combined With Chemotherapy Compared With Chemotherapy Alone for Triple-Negative Breast Cancer: A Systematic Review and Meta-Analysis.

BACKGROUND: It is still controversial whether immune checkpoint inhibitors (ICIs) can improve the curative effect when added to original standard chemotherapy treatment for triple-negative breast cancer (TNBC). We compared their antitumor efficacy and adverse effects (AEs) to make a better clinical decision. METHODS: Seven databases were searched for eligible articles. Progression-free survival (PFS), overall survival (OS), and AEs were measured as the primary outcomes. RESULTS: Nine randomized controlled trials (RCTs) involving 4,501 patients were included. ICI+chemotherapy treatment achieved better PFS (hazard ratio [HR]: 0.78, [0.70-0.86], p < 0.00001), OS (HR: 0.86, [0.74-0.99], p = 0.04), and complete response (584/1,106 vs. 341/825, risk ratio [RR]: 1.38, [1.01-1.89], p = 0.04). With the prolongation of survival, the survival advantage of ICI+chemotherapy increased compared with chemotherapy. Subgroup analysis suggested that the addition of ICIs might not have a better effect in Asian patients, patients with locally advanced disease, or patients with brain metastases. In the toxicity analysis, more Grade 3-5 AEs and serious AEs were found in the ICI+chemotherapy group. For Grade 3-5 AEs, more cases of diarrhea, severe skin reactions, pneumonitis, hepatitis, and adrenal insufficiency were related to the ICI+chemotherapy group. CONCLUSIONS: ICI+chemotherapy appears to be better than chemotherapy alone for TNBC treatment, with better OS and PFS. However, its high rates of serious AEs need to be taken seriously. SYSTEMATIC REVIEW REGISTRATION: PROSPERO Registration: CRD42021276394.

Albendazole solid dispersions prepared using PEG6000 and Poloxamer188: formulation, characterization and in vivo evaluation.

This study aimed to optimize the preparation process of albendazole (ABZ) solid dispersion (SD) and enhance its dissolution rate and oral bioavailability in dogs. The ABZ-SD formulations were prepared by a fusion method with ABZ and polyethylene glycol 6000 (PEG 6000), poloxamer 188 (P 188) polymers at various weight ratios or the combination of PEG 6000&P 188. The characterizations of the optimal formulations were performed by scanning electron microscopy (SEM), powder X-ray diffraction (PXRD), Fourier transform infrared spectroscopy (FTIR), in vitro dissolution test and molecular docking. The in vivo pharmacokinetic study was conducted in beagle dogs. As a result, ABZ solid dispersion based on PEG 6000&P 188 (1:2) was successfully prepared. The ABZ-SD formulation could significantly improve the apparent solubility and dissolution rate of ABZ compared with commercial tablets. Furthermore, the water solubility of ABZ-SD was improved mainly based on hydrogen bond association. Besides, at an oral dosage of 15 mg/kg ABZ, the SDs had higher Cmax values and areas under the curve (AUCs) compared to those of commercial ABZ tablets. Preparation of ABZ-loaded SDs by PEG 6000&P 188 is a promising strategy to improve the oral bioavailability of ABZ.

Homology Modeling and Virtual Screening to Discover Potent Inhibitors Targeting the Imidazole Glycerophosphate Dehydratase Protein in Staphylococcus xylosus.

The imidazole glycerophosphate dehydratase (IGPD) protein is a therapeutic target for herbicide discovery. It is also regarded as a possible target in Staphylococcus xylosus (S. xylosus) for solving mastitis in the dairy cow. The 3D structure of IGPD protein is essential for discovering novel inhibitors during high-throughput virtual screening. However, to date, the 3D structure of IGPD protein of S. xylosus has not been solved. In this study, a series of computational techniques including homology modeling, Ramachandran Plots, and Verify 3D were performed in order to construct an appropriate 3D model of IGPD protein of S. xylosus. Nine hits were identified from 2,500 compounds by docking studies. Then, these nine compounds were first tested in vitro in S. xylosus biofilm formation using crystal violet staining. One of the potential compounds, baicalin was shown to significantly inhibit S. xylosus biofilm formation. Finally, the baicalin was further evaluated, which showed better inhibition of biofilm formation capability in S. xylosus by scanning electron microscopy. Hence, we have predicted the structure of IGPD protein of S. xylosus using computational techniques. We further discovered the IGPD protein was targeted by baicalin compound which inhibited the biofilm formation in S. xylosus. Our findings here would provide implications for the further development of novel IGPD inhibitors for the treatment of dairy mastitis.

Comparative Proteomic Analysis Provides insight into the Key Proteins as Possible Targets Involved in Aspirin Inhibiting Biofilm Formation of Staphylococcus xylosus.

Staphylococcus xylosus is an opportunistic pathogen that causes infection in humans and cow mastitis. And S. xylosus possesses a strong ability to form biofilms in vitro. As biofilm formation facilitates resistance to antimicrobial agents, the discovery of new medicinal properties for classic drugs is highly desired. Aspirin, which is the most common active component of non-steroidal anti-inflammatory compounds, affects the biofilm-forming capacity of various bacterial species. We have found that aspirin effectively inhibits biofilm formation of S. xylosus by Crystal violet (CV) staining and scanning electron microscopy analyses. The present study sought to elucidate possible targets of aspirin in suppressing S. xylosus biofilm formation. Based on an isobaric tag for relative and absolute quantitation (iTRAQ) fold-change of >1.2 or <0.8 (P-value < 0.05), 178 differentially expressed proteins, 111 down-regulated and 67 up-regulated, were identified after application of aspirin to cells at a 1/2 minimal inhibitory concentration. Gene ontology analysis indicated enrichment in metabolic processes for the majority of the differentially expressed proteins. We then used the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway database to analyze a large number of differentially expressed proteins and identified genes involved in biosynthesis of amino acids pathway, carbon metabolism (pentose phosphate and glycolytic pathways, tricarboxylic acid cycle) and nitrogen metabolism (histidine metabolism). These novel proteins represent candidate targets in aspirin-mediated inhibition of S. xylosus biofilm formation at sub-MIC levels. The findings lay the foundation for further studies to identify potential aspirin targets.