Diagnostic accuracy of ESR1 mutation detection by cell-free DNA in breast cancer: a systematic review and meta-analysis of diagnostic test accuracy.

BACKGROUND: Estrogen receptors express in nearly 70% of breast cancers (ER-positive). Estrogen receptor alpha plays a fundamental role as a significant factor in breast cancer progression for the early selection of therapeutic approaches. Accordingly, there has been a surge of attention to non-invasive techniques, including circulating Cell-free DNA (ccfDNA) or Cell-Free DNA (cfDNA), to detect and track ESR1 genotype. Therefore, this study aimed to examine the diagnosis accuracy of ESR1 mutation detection by cell-free DNA in breast cancer patientsthrough a systematic review and comprehensive meta-analysis. METHODS: PubMed, Embase, and Web of Science databases were searched up to 6 April 2022. Diagnostic studies on ESR1 measurement by cfDNA, which was confirmed using the tumour tissue biopsy, have been included in the study. The sensitivity, specificity, accuracy, positive predictive value (PPV), negative predictive value (NPV), positive likelihood ratio (PLR) and negative likelihood ratio (NLR) were considered to analyse the data. RESULTS: Out of 649 papers, 13 papers with 15 cohorts, including 389 participants, entered the meta-analyses. The comprehensive meta-analysis indicated a high sensitivity (75.52, 95% CI 60.19-90.85), specificity (88.20, 95% CI 80.99-95.40), and high accuracy of 88.96 (95% CI 83.23-94.69) for plasma ESR1. We also found a moderate PPV of 56.94 (95% CI 41.70-72.18) but a high NPV of 88.53 (95% CI 82.61-94.44). We also found an NLR of 0.443 (95% CI 0.09-0.79) and PLR of 1.60 (95% CI 1.20-1.99). CONCLUSION: This systematic review and comprehensive meta-analysis reveal that plasma cfDNA testing exhibits high sensitivity and specificity in detecting ESR1 mutations in breast cancer patients. This suggests that the test could be a valuable diagnostic tool. It may serve as a dependable and non-invasive technique for identifying ESR1 mutations in breast cancer patients. However, more extensive research is needed to confirm its prognostic value.

The role of aquaporin 4 in brain tumors: implications for pathophysiology, diagnosis and therapy.

Primary brain tumors are a heterogeneous group of tumors that arise from cells intrinsic to the central nervous system (CNS). Aquaporin-4 (AQP4) has been implicated in the pathogenesis of brain tumors. Previous reports have documented a relationship between AQP4 and several molecular pathways associated with the etiology of brain tumors, such as apoptosis, invasion and cell migration. AQP4 affects apoptosis via cytochrome C, Bad and Bcl-2, as well as invasion and migration via IDO1/TDO-Kyn-AhR axis, lncRNA LINC00461, miR-216a, miRNA-320a and MMPs. In addition, inhibition of AQP4 mitigates the progression of brain tumors. This review summarizes current knowledge and evidence regarding the relationship between AQP4 and brain tumors, and the mechanisms involved.

Evaluation of hepatic injury in chronic hepatitis B and C using APRI and FIB-4 indices compared to fibroscan results.

Background: Hepatitis B (HBV) and hepatitis C viruses (HCV) are significant causes of liver disease worldwide. Liver fibrosis (LF) is a complication of chronic liver damage caused by HBV and HCV due to our limited knowledge comparing the diagnostic performance of platelet to aspartate aminotransferase ratio index (APRI) and fibrosis-4 (FIB-4) index with fibroscan. Methods: This study evaluated liver damage in HBV and HCV using APRI, FIB-4, and fibroscan indices. This retrospective cohort descriptive-analytical study was conducted on patients with HBV and HCV. This study uses laboratory results and imaging to investigate liver damage in chronic HBV and HCV patients. APRI and FIB-4 were computed based on laboratory results. Results: A total of 185 patients (82 hepatitis B and 103 hepatitis C) were included in the study. Thirteen patients had liver cirrhosis. There was no statistically significant difference between the fibroscan results in the two groups (P=0.99). The HBV group's mean APRI and FIB-4 were lower than HCV, but no significant difference was observed (P>0.05). Our results in HBV and HCV patients showed that APRI and FIB-4 accomplished well anticipating cirrhosis with an area under the receiver operating characteristic curve (AUC) of 0.771-0.845 and 0.871-0.910, respectively. Conclusion: Fibroscan is a powerful tool superior to APRI and FIB-4 in predicting LF and cirrhosis. Nevertheless, APRI and FIB-4 are inexpensive and non-invasive indicators with acceptable efficacy in predicting advanced fibrosis or cirrhosis. However, these two measures are not reliable in low-grade fibrosis.

Evaluation of IFNAR2 and TYK2 transcripts' prognostic role in COVID-19 patients: a retrospective study.

Background and objectives: This study aimed to investigate the possible prognostic significance of interferon alpha-beta receptor subunit 2 (IFNAR2) and tyrosine kinase 2 (TYK2) expressions. Methods: We conducted a retrospective study including COVID-19 adult patients. All blood samples were collected before any interventions. The expressions of IFNAR2 and TYK2 were assessed using real-time PCR in venous blood samples of 54 cases and 56 controls. The transcript quantities of IFNAR2 and TYK2 genes were assessed using a Delta-Ct method. Results: Our findings show no significant differences in gene expression levels for IFNAR2 and TYK2 between patients who required oxygen (O2) therapy and those who did not (p-value = 0.732 and p-value = 0.629, respectively). Likewise, there were no significant differences in IFNAR2 and TYK2 expressions between patients hospitalized for less than 7 days and those hospitalized for 7 days or more (p-value = 0.455 and p-value = 0.626, respectively). We also observed a weak correlation between IFNAR2 expression and CRP (p-value = 0.045, r = 0.192). There was a negative correlation between the expression levels of IFNAR2 and TYK2 transcripts in COVID-19 patients (p-value = 0.044; partial correlation coefficient = -0.283). Additionally, IFNAR2 and TYK2 were significantly downregulated in the COVID-19 group compared to healthy subjects (p-value = 0.002 and p-value = 0.028, respectively). However, neither IFNAR2 nor TYK2 expression was significantly different between the case subgroups based on COVID-19 severity. The IFNAR2 ΔΔCt (B = -0.184, 95% CI: -0.524-0.157, p-value = 0.275) and the TYK2 ΔΔCt (B = 0.114, 95% CI: -0.268-0.496, p-value = 0.543) were not found to be significant predictors of hospitalization duration. The area under the curve (AUC) for IFNAR2 expression is 0.655 (p-value = 0.005, 95% CI: 0.554-0.757), suggesting its poor discriminative value. Conclusion: We were unable to comment definitively on the prognostic power of IFNAR2 and TYK2 expressions in COVID-19 patients, and larger-scale studies are needed. The principal limitations of this study included the lack of longitudinal analysis and limited sample size.

Senility and COVID-19 as two possible risk factors for loss of consciousness: A rare case report.

Introduction: and Importance: More than two years after the start of the COVID-19 pandemic, the world is still grappling with this dilemma. COVID-19 covers a wide range of symptoms. Loss of consciousness (LOC) is a very rare symptom that can threaten a patient's life and blur the prognosis of recovery. Case presentation: An 89-year-old woman was presented to the emergency department with LOC (Glasgow Coma Scale (GCS) score = 3) without any history of the underlying disease and was immediately admitted to the intensive care unit. In brain imaging, severe small vessel disease was diagnosed by observing partial dilatation of the ventricles, sulcus, and hypodense areas in the periventricular area. Lung imaging propounded COVID-19 by detecting the ground glass pattern with 50%-75% involvement. After detecting severe acute respiratory syndrome coronavirus 2 nucleic acid by reverse transcription-polymerase chain reaction, COVID-19 treatment was performed according to the national protocol. Finally, she was discharged after 26 days of hospitalization with partial recovery. Clinical discussion: COVID-19-induced cytokine storm along with old age appears to increase LOC risk. It can be claimed that COVID-19-induced LOC can be considered as one of the symptoms of COVID-19 in the elderly population. Therefore, more attention should be paid to this population, which is more at risk. Conclusion: Few reports illustrate the LOC as a COVID-19 presentation. This report highlights the fact that older people are more at risk for COVID-19-induced LOC than other age groups and should be given more care.

Trends in the Prevalence of Amphotericin B-Resistance (AmBR) among Clinical Isolates of Aspergillus Species.

The challenges of the invasive infections caused by the resistant Aspergillus species include the limited access to antifungals for treatment and high mortality. This study aimed to provide a global perspective of the prevalence of amphotericin B resistance (AmBR), geographic distribution, and the trend of AmBR from 2010 to 2020. To analyze the prevalence of in vitro AmBR in clinical Aspergillus species, we reviewed the literature and identified a total of 72 articles. AmBR was observed in 1128 out of 3061 Aspergillus terreus (36.8%), 538 out of 3663 Aspergillus flavus (14.9%), 141 out of 2691 Aspergillus niger (5.2%), and 353 out of 17,494 Aspergillus fumigatus isolates (2.01%). An increasing trend in AmB-resistant isolates of A. fumigatus and a decreasing trend in AmB-resistant A. terreus and A. flavus isolates were observed between 2016 and 2020. AmB-resistant A. terreus and A. niger isolates, accounting for 40.4% and 20.9%, respectively, were the common AmB-resistant Aspergillus species in Asian studies. However, common AmB-resistant Aspergillus species reported by European and American studies were A. terreus and A. flavus isolates, accounting for 40.1% and 14.3% in 31 studies from Europe and 25.1% and 11.7% in 14 studies from America, respectively. The prevalence of AmB-resistant A. niger in Asian isolates was higher than in American and European. We found a low prevalence of A. terreus in American isolates (25.1%) compared to Asian (40.4%) and European (40.1%). Future studies should focus on analyzing the trend of AmBR on a regional basis and using the same methodologies.

Helicobacter pylori Infection and Non-alcoholic Fatty Liver Disease: A Systematic Review and Meta-Analysis.

Since numerous studies have stated that there may be a relationship between Helicobacter pylori infection and nonalcoholic fatty liver disease, and because of the high prevalence of both conditions worldwide, this study investigated the risk of non-alcoholic fatty liver disease in patients infected with H. pylori. Following a systematic review of PubMed, Scopus, Web of Science and Embase, and a search in Google Scholar using MeSH terms such as H. pylori and non-alcoholic fatty liver disease, the relevant papers up to November 2020 were reviewed. All cohort, case-control, and cross-sectional studies that examined the risk of developing non-alcoholic fatty liver disease in patients infected with H. pylori entered this study. A meta-analysis was conducted in STATA 11. This systematic review examined 22 papers with 117 117 participants (33 711 patients infected with H. pylori and 83 406 participants as control) and 20 studies were subjected to meta-analysis The results indicated a 22% to 27% increase in the risk of developing non-alcoholic fatty liver disease in patients infected with H. pylori (crude odds ratio: 1.27, 95% CI: 1.17-1.33; and adjusted odds ratio: 1.22, 95% CI: 1.09-1.35). According to the subgroup analysis, the study region, sample size, and the method of diagnosing H. pylori were the factors contributing to the high heterogeneity. The meta-analysis revealed the increased risk of developing non-alcoholic fatty liver disease in patients infected with H. pylori. This indicates that H. pylori is a serious risk factor in patients susceptible to NAFLD.

IFI27 transcription is an early predictor for COVID-19 outcomes, a multi-cohort observational study.

Purpose: Robust biomarkers that predict disease outcomes amongst COVID-19 patients are necessary for both patient triage and resource prioritisation. Numerous candidate biomarkers have been proposed for COVID-19. However, at present, there is no consensus on the best diagnostic approach to predict outcomes in infected patients. Moreover, it is not clear whether such tools would apply to other potentially pandemic pathogens and therefore of use as stockpile for future pandemic preparedness. Methods: We conducted a multi-cohort observational study to investigate the biology and the prognostic role of interferon alpha-inducible protein 27 (IFI27) in COVID-19 patients. Results: We show that IFI27 is expressed in the respiratory tract of COVID-19 patients and elevated IFI27 expression in the lower respiratory tract is associated with the presence of a high viral load. We further demonstrate that the systemic host response, as measured by blood IFI27 expression, is associated with COVID-19 infection. For clinical outcome prediction (e.g., respiratory failure), IFI27 expression displays a high sensitivity (0.95) and specificity (0.83), outperforming other known predictors of COVID-19 outcomes. Furthermore, IFI27 is upregulated in the blood of infected patients in response to other respiratory viruses. For example, in the pandemic H1N1/09 influenza virus infection, IFI27-like genes were highly upregulated in the blood samples of severely infected patients. Conclusion: These data suggest that prognostic biomarkers targeting the family of IFI27 genes could potentially supplement conventional diagnostic tools in future virus pandemics, independent of whether such pandemics are caused by a coronavirus, an influenza virus or another as yet-to-be discovered respiratory virus.