Diagnostic Value of Non-invasive Liver Function Tests in Liver Fibrosis and Changes in These Parameters Post-metabolic Surgery.

PURPOSE: This study aimed to ascertain the diagnostic accuracy of non-invasive liver function tests in liver fibrosis and assess their changes after metabolic surgery. MATERIALS AND METHODS: 1005 individuals with severe obesity who were referred for metabolic surgery were analysed. All participants had blood samples taken for liver enzymes and lipid profile. In addition, hepatic indexes, including AAR, APRI, NFS and Fibrosis-4 (FIB4), were checked. Furthermore, all participants underwent two-dimensional shear wave elastography (2D-SWE). All investigations were repeated 6-8 months after metabolic surgery. The receiver operating characteristic (ROC) curve and the area under the ROC curve was utilised to determine the optimal cut-off values for baseline study parameters. Logistic regression was applied to predict the relationship between study parameters-as predictors-and change in 2D-SWE. RESULTS: AST/ALT (AAR) was the most sensitive (79%) pre-operative non-invasive serological marker for detecting liver fibrosis, whereas NAFLD Fibrosis Score (NFS) was the most specific (84%). AST/upper limit of the normal AST range × 100/platelets (× 109/L) (APRI) showed a positive correlation with 2D-SWE post-metabolic surgery (p-value = 0.021). Regression analysis from both adjusted and unadjusted models showed that baseline AAR was a predictor of postoperative liver status in terms of hepatic fibrosis. CONCLUSION: AAR has a high sensitivity, whereas NFS exhibits a high specificity in diagnosing liver fibrosis. The authors recommend using both investigations in conjunction with 2D-SWE to increase the likelihood of detecting liver fibrosis.

The effect of concomitant use of Colony-Stimulating factors on bleomycin pulmonary toxicity - A systematic review and meta-analysis.

BACKGROUND: Changes in the incidence of bleomycin pulmonary toxicity (BPT) as a result of adding colony-stimulating factors (CSF) to bleomycin regimens has been investigated in numerous studies. We performed a systematic review and meta-analysis to assess the outcomes of these studies. METHODS: A systematic search was performed using Pubmed, Scopus, Web of Science, and Embase on April 2021. Studies evaluating the incidence of BPT in patients receiving bleomycin with and without CSF were included. In addition, meta-analysis was performed by pooling odds ratios using R. RESULTS: Out of 340 obtained records, our qualitative and quantitative analysis included 3234 and 1956 patients from 22 and 14 studies, respectively. The quantitative synthesis showed that addition of CSF significantly increased the risk of BPT incidence (OR = 1.82, 95 % CI: 1.37-2.40, p < 0.0001; I2 = 10.7 %). Subgroup analysis did not show any association between continent, bleomycin dose, cancer type, type of study, and pulmonary function test with BPT incidence. CONCLUSION: This systematic review and meta-analysis showed that co-administration of CSF with bleomycin increases the incidence of BPT. The physicians need to consider this finding while deciding the best strategy for this cohort of patients.

MiR-212 value in prognosis and diagnosis of cancer and its association with patient characteristics: a systematic review and meta-analysis.

BACKGROUND: Delayed cancer diagnosis and inefficient cancer prognosis determination are problems faced in cancer diagnosis and treatment. MicroRNAs (miRs), especially miR-212, have shown a promise in cancer diagnosis and prognosis. Herein, we performed a systematic review and meta-analysis to assess the prognostic and diagnostic value of miR-212 level in cancer and evaluated its association with patient characteristics. METHODS: A fully electronic literature search using related keywords was performed in PubMed, Scopus, Web of Science, Embase, and ScienceDirect databases by June 6, 2021, with no time or language restriction. Meta-analysis was performed to pool survival prognosis data using hazard ratio (HR), association using odds ratio (OR), and diagnostic data using sensitivity, specificity, and diagnostic odds ratio (DOR). Sub-group analysis and meta-regression were performed as appropriate. RESULTS: Results of 28 studies on 1880 patients showed a poor cancer prognosis with high levels of miR-212 in pancreatic ductal adenocarcinoma (PDAC, HR = 2.451 [1.447-4.149]), and a poor cancer prognosis with low levels of miR-212 in other cancers (HR = 2.514 [2.162-2.923]). Higher alpha-fetoprotein (AFP) level and Edmondson-Steiner grade were factors associated with miR-212 low level incidence. Diagnostic odds ratio 10.688 (3.644-31.348) and SROC AUC of 0.84 confirmed high diagnostic performance of miR-212. CONCLUSION: Our systematic review and meta-analysis results confirm miR-212 high value in cancer prognosis and diagnosis. High level of miR-212 showed poor prognosis in PDAC and low level of miR-212 showed poor prognosis in other cancers. in conclusion, miR-212 could be a novel potential biomarker in cancer diagnosis and prognosis.

Design and synthesis of targeted star-shaped micelle for guided delivery of camptothecin: In vitro and in vivo evaluation.

This study aimed to synthesize a star-shaped micelle using 3-azido-2,2-bis(azidomethyl)propan-1-ol (pentaerythritol triazide) core, as an initiator for the synthesis of three-arm polylactic acid (PLA) block. Then, the ends of the PLA arms were converted to PLA triazide followed by conjugation to the three alkyne-PEG-maleamide through click reaction. The maleamide ends were available for coupling with sulfhydryl-modified DNA aptamer against epithelial cell adhesion molecule in order to offer targeted delivery of encapsulated drug, camptothecin to the site of action. The successful synthesis of the star-shaped polymers was confirmed via1HNMR. Hydrophobic anti-cancer drug, camptothecin was encapsulated into the micelles core implementing solvent switching method providing loading content (LC%) and encapsulation efficiency (EE%) of 3.7 ± 0.4 and 73.7 ± 8.2, respectively. The size of both non-targeted and aptamer-targeted micelles was determined to be 154 and 192 nm, respectively with polydispersity index below 0.3. In vitro drug release evaluation at 37 °C, pH 7.4 showed a controlled release pattern for camptothecin during 72 h. In vitro cytotoxicity of the prepared non-targeted and targeted micelles was carried out on human colorectal adenocarcinoma (HT29) and mouse colon carcinoma (C26) as EpCAM positive cell lines and Chinese hamster ovary (CHO) as EpCAM negative cell line. The results verified significantly higher cytotoxicity of the targeted micelles on HT29 and C26 cell lines, while no obvious difference was observed between targeted and non-targeted formulation on CHO cell line. The in vivo therapeutic efficiency investigation on BALB/c C26 tumor-bearing mice showed superior capability of the targeted formulation on tumor suppression and survival rate of the treated mice. The developed platform exhibited excellent characteristics to diminish camptothecin drawbacks and its adverse effects while considerably increasing its therapeutic index.

Opium as a carcinogen: A systematic review and meta-analysis.

BACKGROUND: Opium and its pyrolysates have been investigated as potential carcinogenic material through several studies in different body systems; however, the results were controversial and no consensus was achieved with this regard. Thus, we aimed to systematically review and meta-analyze all existed evidence regarding association between opium consumption and cancer. METHODS: Four major electronic databases including ISI Web of Science, PubMed, Scopus, and Embase along with Magiran and SID were searched thoroughly for all published articles from inception up to September 25, 2020. All studies were appraised critically by Newcastle Ottawa Scale (NOS) checklist. Relevant demographic data and the intended results of the selected studies were extracted and their Odds ratios (OR) were pooled using Comprehensive Meta-analysis (CMA). The cumulative risk of opium for developing different cancers was calculated. FINDINGS: 34 studies comprised of 18,230 individuals were entered in our systematic review and finally 32 publications were enrolled in meta-analysis. Overall, using the random effects model, opium consumption was associated with increased rate of malignancies in both minimally[OR = 4.14 95%CI = (3.32-5.15)] and fully adjusted [OR = 4.35 95%CI = (3.36-5.62)] analyses. Moreover, using random effects fully adjusted model, the subgroup analysis revealed increased risk for larynx [OR = 9.58 95%CI = (6.31-14.53)], respiratory [OR = 9.02 95%CI = (6.27-12.96)], head and neck [OR = 8•03 95%CI = (4.03-16.00)], and colon [OR=5.58 95%CI = (3.14-9.92)] cancers for opium consumers compared to non-consumers. INTERPRETATION: Opium consumption is highly associated with all reported types of cancers, especially in fully adjusted model; however, basic pathophysiology should be further investigated. FUNDING: None.

Cardiac Complications in COVID-19: A Systematic Review and Meta-analysis.

BACKGROUND: The newly emerged coronavirus disease 2019 (COVID-19) seems to involve different organs, including the cardiovascular system. We systematically reviewed COVID-19 cardiac complications and calculated their pooled incidences. Secondarily, we compared the cardiac troponin I (cTnI) level between the surviving and expired patients. METHODS: A systematic search was conducted for manuscripts published from December 1, 2019 to April 16, 2020. Cardiovascular complications, along with the levels of cTnI, creatine kinase (CK), and creatine kinase MB (CK-MB) in hospitalized PCR-confirmed COVID-19 patients were extracted. The pooled incidences of the extracted data were calculated, and the unadjusted cTnI level was compared between the surviving and expired patients. RESULTS: Out of 1094 obtained records, 22 studies on a total of 4,157 patients were included. The pooled incidence rate of arrhythmia was 10.11%. Furthermore, myocardial injury had a pooled incidence of 17.85%, and finally, the pooled incidence for heart failure was 22.34%. The pooled incidence rates of cTnI, CK-MB, and CK elevations were also reported at 15.16%, 10.92%, and 12.99%, respectively. Moreover, the pooled level of unadjusted cTnI was significantly higher in expired cases compared with the surviving (mean difference = 31.818, 95% CI = 17.923-45.713, P value <0.001). CONCLUSION: COVID-19 can affect different parts of the heart; however, the myocardium is more involved.

Association between carotid intima-media thickness and ulcerative colitis: a systematic review and meta-analysis.

BACKGROUND: Early detection of atherosclerosis is an essential means of decreasing cardiovascular events and its associated mortality. Systemic inflammatory diseases such as ulcerative colitis (UC), are thought to be a contributing factor to atherosclerosis due to the rise of inflammatory cytokines. OBJECTIVE: The aim of this systematic review and meta-analysis was to assess the association between atherosclerosis and UC. METHODS: This systematic review and meta-analysis was performed in February 2017 with no date restrictions. PubMed, Cochrane Library and Embase were searched to discover all available observational studies on atherosclerosis among UC patients. The STROBE criteria were used to assess the quality of the included articles. Heterogeneity was assessed by the I-square statistic and publication bias with funnel plot and Egger's regression test. Overall summary mean difference was calculated as study effect size using random effect model. Comprehensive Meta-Analysis Software version 2.2 was used to perform analyses. RESULTS: A total of 5 articles met our eligibility criteria. We included a sum of 206 UC patients and 229 non-UC individuals in our review with a mean difference of c-IMT ranged from 0.03±0.0 to 0.16±0.03 mm, and a pooled mean difference of 0.127 mm (95% CI 0.058-0.195: I2 =90.266%). Potential publication bias did not exist for the UC. CONCLUSION: Our findings showed significant differences in carotid intima-media thickness among UC and Non-UC groups, making c-IMT a viable choice as a predicting marker for atherosclerosis. Thus, we suggest that policy makers assess and consider its application in future protocols for the follow up and management of UC patients.

Growth Inhibition and Apoptosis Induction of Essential Oils and Extracts of Nepeta cataria L. on Human Prostatic and Breast Cancer Cell Lines.

Nepeta cataria L. has been used in traditional medicine of some countries. Here the cytotoxic and apoptogenic activity of methanol extracts, n-hexane, dichloromethane, ethyl acetate, n-butanol, and acqueous extracts and the essential oil obtained from the aerial parts of the plant were evaluated with PC3, DU-145 and MCF-7 cell lines. Cell viability, histograms of PI stained fragmented DNA in apoptotic cells and Western blot analysis of proteins involved in the cascade of apoptosis were compared in all samples. Thirty components were identified as volatile, representing 99.7% of essential oil composition after GC-MS analysis of the oil obtained from aerial parts of the N. cataria by hydro-distillation. The major oil components of the essential oil were nepetalactone stereoisomers. Comparing IC50 values showed estrogen receptor positive PC3 cells were more sensitive to the cytotoxic effects of N. cataria in comparison with low hormone-receptor presenting DU-145 cells. Among multiple extracts and essential oils of the plant, only the ethyl acetate extract could significantly decrease cell viability in PC3 cells, in a concentration dependent manner. Ethyl acetate extract of N. cataria treated cells showed a sub-G1 peak in PC3 cells in a concentration dependent manner that indicates the involvement of an apoptotic process in ethyl acetate extract-induced cell death. Western blotting analysis showed that in PC3 cells treated with ethyl acetate (48 h) caspase 3 and PARP were cleaved to active forms. Overall, the results suggest that further analytical elucidation of N. cataria in respect to finding new cytotoxic chemicals with anti-tumor activity is warranted.