Hepatic encephalopathy complications are diminished by piracetam via the interaction between mitochondrial function, oxidative stress, inflammatory response, and locomotor activity.

Background: of the study: Hepatic encephalopathy (HE) is a complication in which brain ammonia (NH4+) levels reach critically high concentrations because of liver failure. HE could lead to a range of neurological complications from locomotor and behavioral disturbances to coma. Several tactics have been established for subsiding blood and brain NH4+. However, there is no precise intervention to mitigate the direct neurological complications of NH4+. Purpose: It has been found that oxidative stress, mitochondrial damage, and neuro-inflammation play a fundamental role in NH4+ neurotoxicity. Piracetam is a drug used clinically in neurological complications such as stroke and head trauma. Piracetam could significantly diminish oxidative stress and improve brain mitochondrial function. Research methods: In the current study, piracetam (100 and 500 mg/kg, oral) was used in a mice model of HE induced by thioacetamide (TA, 800 mg/kg, single dose, i.p). Results: Significant disturbances in animals' locomotor activity, along with increased oxidative stress biomarkers, including reactive oxygen species formation, protein carbonylation, lipid peroxidation, depleted tissue glutathione, and decreased antioxidant capacity, were evident in the brain of TA-treated mice. Meanwhile, mitochondrial permeabilization, mitochondrial depolarization, suppression of dehydrogenases activity, and decreased ATP levels were found in the brain of the TA group. The level of pro-inflammatory cytokines was also significantly high in the brain of HE animals. Conclusion: It was found that piracetam significantly enhanced mice's locomotor activity, blunted oxidative stress biomarkers, decreased inflammatory cytokines, and improved mitochondrial indices in hyperammonemic mice. These data suggest piracetam as a neuroprotective agent which could be repurposed for the management of HE.

Prevalence of Fungal Drug Resistance in COVID-19 Infection: a Global Meta-analysis.

Purpose: Secondary bacterial or fungal infections are one of the most important medical complications among patients with Coronavirus Disease 2019 (COVID-19). The emergence of multidrug-resistant (MDR) candida can cause many problems such as treatment failure, adverse clinical outcomes, and even disease outbreaks. This systematic review and meta-analysis aims to investigate the prevalence and outcomes of fungal drug-resistant in COVID-19 patients. Methods: PubMed, Embase, Scopus, Cochrane Library, and Web of Science databases were searched for peer reviewed-articles published in English up to May 20, 2021. Heterogeneity across studies was evaluated using Cochrane's Q test and the I2 index. The pooled point prevalence and their corresponding 95% confidence intervals (CIs) were considered to estimate the prevalence of fungal drug resistance infection in COVID-19 patients. Results: Eight eligible articles were included in our meta-analysis. The number of COVID-19 patients with fungal co-infection varied from 5 to 35 among selected studies. The overall pooled prevalence of fungal drug resistance among patients with co-infections of fungal and COVID-19 was 69% (95% CI: 37%, 94%) by using a random-effects model. In terms of specific species, the pooled meta-analysis for Candida Auris was estimated to be 100% (95%CI: 98%, 100%; I2 = 0%), for Multi-Candida 59% (95%CI: 38%, 79%; I2 = 12.5%), and for Aspergillus 15% (95%CI: 0%, 42%; I2 = 0%). Conclusion: Our study shows the high prevalence of fungal drug resistance in COVID-19 patients and emphasizes the need to strengthen antimicrobial stewardship programs, close monitoring for treatment failure, and the emergence of resistance upon treatment. Supplementary Information: The online version contains supplementary material available at 10.1007/s12281-022-00439-9.

Immune Checkpoint Inhibitors in Cancer Therapy.

The discovery of immune checkpoint proteins such as PD-1/PDL-1 and CTLA-4 represents a significant breakthrough in the field of cancer immunotherapy. Therefore, humanized monoclonal antibodies, targeting these immune checkpoint proteins have been utilized successfully in patients with metastatic melanoma, renal cell carcinoma, head and neck cancers and non-small lung cancer. The US FDA has successfully approved three different categories of immune checkpoint inhibitors (ICIs) such as PD-1 inhibitors (Nivolumab, Pembrolizumab, and Cemiplimab), PDL-1 inhibitors (Atezolimumab, Durvalumab and Avelumab), and CTLA-4 inhibitor (Ipilimumab). Unfortunately, not all patients respond favourably to these drugs, highlighting the role of biomarkers such as Tumour mutation burden (TMB), PDL-1 expression, microbiome, hypoxia, interferon-γ, and ECM in predicting responses to ICIs-based immunotherapy. The current study aims to review the literature and updates on ICIs in cancer therapy.

Blood Trace Element Status in Multiple Sclerosis: a Systematic Review and Meta-analysis.

The aim of this meta-analysis was to investigate whether the blood concentrations of patients with multiple sclerosis (MS) are associated with those of the healthy control group in terms of trace elements including zinc (Zn), iron (Fe), manganese (Mn), magnesium (Mg), selenium (Se), and copper (Cu). A comprehensive search was performed in online databases including PubMed, Scopus, Embase, and Web of Science for studies, which have addressed trace elements in MS up to July 23, 2020. The chi-square test and I2 statistic were utilized to evaluate inter-study heterogeneity across the included studies. Weighted mean differences (WMDs) and corresponding 95% CI were considered as a pooled effect size (ES). Twenty-seven articles (or 32 studies) with a total sample comprised of 2895 participants (MS patients (n = 1567) and controls (n = 1328)) were included. Pooled results using random-effects model indicated that the levels of Zn (WMD = - 7.83 mcg/dl, 95% CI = - 12.78 to - 2.87, Z = 3.09, P = 0.002), and Fe (WMD = - 13.66 mcg/dl, 95% CI = - 23.13 to - 4.19, Z = 2.83, P = 0.005) were significantly lower in MS patients than in controls. However, it was found that levels of Mn (WMD = 0.03 mcg/dl, 95% CI = 0.01 to 0.04, Z = 2.89, P = 0.004) were significantly higher in MS patients. Yet, no significant differences were observed in the levels of Mg, Se, and Cu between both groups. This meta-analysis revealed that the circulating levels of Zn and Fe were significantly lower in MS patients and that Mn level was significantly higher than those in the control group. However, it was found that there was no significant difference between MS patients and controls with regard to levels of Mg, Se, and Cu.

Effects of garlic extract on lipid profile in patients with coronary artery disease: A systematic review and meta-analysis of randomised clinical trials.

This meta-analysis was conducted to evaluate the effects of garlic extract on total cholesterol (TC), triglycerides (TG), low-density lipoprotein-cholesterol (LDL-c) and high-density lipoprotein-cholesterol (HDL-c), among the patients with coronary artery disease (CAD). Literature searches were conducted in EMBASE, Scopus, PubMed, Web of Science and Cochrane Library until Sep18th, 2020. Inter-study heterogeneity was examined using Cochrane's Q and I2 tests. The random-effect models were utilised to pool the weighted mean differences (WMDs) and the corresponding 95% confidence intervals (CIs). Six articles were enrolled in the current meta-analysis. Garlic consumption significantly reduced TC levels (WMD -16.32 mg/dL; 95% CI -31.22, -1.43; P = .032). We found no significant effects on TG (WMD -10.93 mg/dL; 95% CI -26.19, 4.32; P = .160), HDL-c (WMD 4.55 mg/dL; 95% CI -1.13, 10.23; P = .116) and LDL-c concentrations (WMD -3.65 mg/dL; 95% CI -13.21, 5.92; P = .455). Significant heterogeneity was observed for HDL-c (I2  = 76.8%). However, the findings of sensitivity analysis revealed that upon exclusion of the potential heterogeneity source, the pooled WMD on HDL-c levels were stable. Garlic supplementation may result in a decrease in TC, but will not affect TG, HDL-c and LDL-c levels among CAD patients.

Laboratory features of severe vs. non-severe COVID-19 patients in Asian populations: a systematic review and meta-analysis.

BACKGROUND: More severe cases of COVID- 19 are more likely to be hospitalized and around one-fifth, needing ICU admission. Understanding the common laboratory features of COVID-19 in more severe cases versus non-severe patients could be quite useful for clinicians and might help to predict the model of disease progression. This systematic review and meta-analysis aimed to compare the laboratory test findings in severe vs. non-severe confirmed infected cases of COVID-19. METHODS: Electronic databases were systematically searched in PubMed, EMBASE, Scopus, Web of Science, and Google Scholar from the beginning of 2019 to 3rd of March 2020. Heterogeneity across included studies was determined using Cochrane's Q test and the I2 statistic. We used the fixed or random-effect models to pool the weighted mean differences (WMDs) or standardized mean differences and 95% confidence intervals (CIs). FINDINGS: Out of a total of 3009 citations, 17 articles (22 studies, 21 from China and one study from Singapore) with 3396 ranging from 12 to1099 patients were included. Our meta-analyses showed a significant decrease in lymphocyte, monocyte, and eosinophil, hemoglobin, platelet, albumin, serum sodium, lymphocyte to C-reactive protein ratio (LCR), leukocyte to C-reactive protein ratio (LeCR), leukocyte to IL-6 ratio (LeIR), and an increase in the neutrophil, alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin, blood urea nitrogen (BUN), creatinine (Cr), erythrocyte Sedimentation Rate (ESR), C-reactive protein (CRP), Procalcitonin (PCT), lactate dehydrogenase (LDH), fibrinogen, prothrombin time (PT), D-dimer, glucose level, and neutrophil to lymphocyte ratio (NLR) in the severe group compared with the non-severe group. No significant changes in white blood cells (WBC), Creatine Kinase (CK), troponin I, myoglobin, IL-6 and K between the two groups were observed. INTERPRETATION: This meta-analysis provides evidence for the differentiation of severe cases of COVID-19 based on laboratory test results at the time of ICU admission. Future well-methodologically designed studies from other populations are strongly recommended.