LipoxinA4 as a Potential Prognostic Marker of COVID-19.

This pilot study aimed to determine early changes of LXA4 levels among the hospitalized patients confirmed as COVID-19 cases following the clinical management and its correlation with commonly used inflammatory markers, including erythrocyte sedimentation rate (ESR), c-reactive protein (CRP), and ferritin. Thirty-one adult hospitalized patients infected with the non-severe COVID-19 were included. LXA4 levels were measured at the baseline and 48-72 hours after hospitalization. Accordingly, ESR and CRP levels were collected on the first day of hospitalization. Moreover, the maximum serum ferritin levels were determined during the five days. LXA4 levels significantly increased at 48-72 hours compared to the baseline. ESR, CRP, and ferritin levels were positively correlated with the increased LXA4. In contrast, aging was shown to negatively correlate with the increased LXA4 levels. LXA4 may be known as a valuable marker to assess the treatment response among non-elderly patients with non-severe COVID-19. Furthermore, LXA4 could be considered as a potential treatment option under inflammatory conditions. Further studies are necessary to clarify LXA4 role in COVID-19 pathogenesis, as well as the balance between such pro-resolving mediators and inflammatory parameters.

Curcumin Upregulates miR-148a to Increase the Chemosensitivity of CD44-Positive Prostate Cancer Stem Cells to Paclitaxel Through Targeting the MSK1/IRS1 axis.

BACKGROUND: In men, prostate cancer (PC) is the second most common cause of cancer-related death. However, paclitaxel resistance is a major challenge in advanced PC. Curcumin, a natural antioxidant, has been demonstrated to have cytotoxic effects on cancer stem cells (CSCs). The goal of this study is to explore if curcumin can help lower chemoresistance to paclitaxel through the regulation of miR-148a-mediated apoptosis in prostate CSCs. METHODS: The 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) assay and 4',6-diamidino-2-phenylindole (DAPi) labeling were used to determine cell survival. Immunohistochemistry was used to detect the expression of P-glycoprotein protein (P-gp) and CD44 proteins. Finally, real-time PCR was used to evaluate the regulatory effects of curcumin and paclitaxel on miR-148a and its target genes. RESULTS: Curcumin and paclitaxel co-treatment significantly reduced the IC50 value in CD44+cells compared to paclitaxel alone. Additionally, combining these drugs considerably increased apoptosis in CD44+cells. We also discovered that when curcumin and paclitaxel were combined, the expression of CD44 and P-gp was significantly reduced compared to paclitaxel alone. Curcumin and paclitaxel co-treatment also increased miR-148a levels and regulated the levels of its target genes MSK1 and IRS1. CONCLUSION: Curcumin may restore paclitaxel sensitivity by raising miR-148a expression and inhibiting its target genes.

Management of a critically ill patient with COVID-19-related fulminant myocarditis: A case report.

A 78-year-old man with COVID-19 infection was admitted. Initial echocardiography indicated left ventricular ejection fraction (LVEF) of 15%, high pulmonary arterial pressure, severe left ventricular dysfunction, mild diastolic dysfunction, mild regurgitation mitral valve, and normal septal thickness. Considering the probable diagnosis of COVID-19-related myocarditis, the patient was early managed with the antivirals, immunomodulatory agents, a high dose of ascorbic acid, melatonin, and immunoglobulin therapy. His clinical condition was improved and his last echocardiography revealed LVEF of 40% and improvement in systolic and diastolic dysfunction. The clinicians should be aware of the potentially lethal cardiac complication of COVID-19, especially in geriatrics.

Relationship between amikacin pharmacokinetics and biological parameters associated with organ dysfunction: a case series study of critically ill patients with intra-abdominal sepsis.

OBJECTIVES: This study aimed to evaluate the relationship between amikacin pharmacokinetics and the biomarkers associated with organ dysfunction in critically ill patients with intra-abdominal sepsis. METHODS: A case series involving critically ill patients with intra-abdominal sepsis who received an amikacin loading dose of 20-25 mg/kg intravenous infusion was studied. The 1-, 2-, 4-, 6- and 24-hour amikacin serum concentrations were measured to calculate the pharmacokinetic parameters. The Sequential Organ Failure Assessment (SOFA) score, white blood cells, neutrophil to lymphocyte ratio, platelet count, serum creatinine, creatinine clearance, bilirubin, partial pressure of oxygen to fraction of inspired oxygen ratio, serum albumin, procalcitonin, lactate level, erythrocyte sedimentation rate (ESR) and C-reactive protein were recorded. A linear regression analysis was performed to examine the relationship between the amikacin pharmacokinetics and the biological parameters. RESULTS: Twenty-one patients were studied. A significant correlation was found between the volume of distribution and ESR (p<0.05, r=0.844). Moreover, drug clearance had a significant inverse correlation with serum lactate (p<0.05, r=-0.603). No other significant correlations were found. CONCLUSIONS: ESR and serum lactate were identified as useful predictors of amikacin pharmacokinetics in critically ill patients with intra-abdominal sepsis and may help guide the selection of appropriate empirical dosing.

Antibiotic therapy in sepsis: No next time for a second chance!

WHAT IS KNOWN AND OBJECTIVE: Sepsis is a life-threatening organ dysfunction associated with a high rate of morbidity and mortality. Appropriate antibiotic therapy remains the cornerstone of sepsis and septic shock management. COMMENT: Although the early initiation of antimicrobial agents in the treatment of sepsis is widely acknowledged, the selection and adjustment to optimal dosage can be equally important. Since significant pathophysiological changes in the critically ill patients lead to altered pharmacokinetics of antibiotics, early consideration of pharmacokinetic/pharmacodynamic (PK/PD) properties is necessary for optimal antibiotic dosing in sepsis and should be integrated in practice. WHAT IS NEW AND CONCLUSION: Where possible, an individualized antibiotic dosing approach through the application of therapeutic drug monitoring (TDM) service should replace the conventional dosing in critically ill patients with sepsis. Finally, antimicrobial stewardship can help improve clinical outcomes.

Clinical utility of measuring expression levels of Stanniocalcin 2 in patients with colorectal cancer.

Stanniocalcin 2 (STC2) is a novel member of the Stanniocalcin family, the function of which remains unclear. Its expression is clinically significant in several cancers. The aim of this study was to evaluate the clinical value of measuring expression levels of STC2 in colorectal cancer (CRC) patients. A total of 47 tumor and matched tumor-free margin samples were obtained during surgery. The STC2 mRNA expression level in tumor and marginal tissue was examined by real-time quantitative PCR. STC2 mRNA expression levels were higher in tumor tissues than the control. (r=0.36, p≤0.02). mRNA expression level of STC2 was significantly associated with tumor size (p≤0.05) and histologic grade (p≤0.05). Our study demonstrated that STC2 was significantly expressed in CRC patients, relative to the control. STC2 can therefore be used as a biomarker to differentiate between tumor borders and margins. Analysis of STC2 gene expression during surgery could be useful in reducing surgical error in tumor removal and increasing overall success of surgery with improved tumor clearance. However, in some cases such as where the tumor is end-stage, the expression of such a biomarker may not be clinically beneficial to record. The consideration of marginal samples as a control group can help reduce the effect of confounding factors such as racial and individual differences.