Empagliflozin to prevent post-operative atrial fibrillation in patients undergoing coronary artery bypass graft surgery: Rationale and design of the EMPOAF trial.

BACKGROUND: Postoperative atrial fibrillation (POAF) is one of the most common types of acute AF and can complicate the treatment course of approximately one third of patients undergoing cardiac surgery. Sodium-glucose cotransporter-2 (SGLT2) inhibitors are among the newest antidiabetic drugs which can be therapeutic options for preventing POAF by different mechanisms. METHODS: Empagliflozin to Prevent POAF (EMPOAF) is an interventional, investigator-initiated, double-blind, placebo-controlled, multicenter, randomized controlled trial which will be conducted in two referral teaching cardiology hospitals in Tehran. Four-hundred ninety-two adult patients who are scheduled for elective isolated coronary artery bypass graft (CABG) surgery will be randomly assigned to one of the groups of intervention (empagliflozin 10 mg daily) or placebo starting at least 3 days before surgery until discharge. Key exclusion criteria are a history of diabetes mellitus, AF, ketoacidosis, or recurrent urinary tract infections along with severe renal or hepatic impairment, unstable hemodynamics, and patients receiving SGLT2 inhibitors for another indication. The primary outcome will be the incidence of POAF. Key secondary endpoints will be the composite rate of life-threatening arrhythmias, postoperative acute kidney injury, hospitalization length, in-hospital mortality, stroke, and systemic embolization. Key safety endpoints will be the rate of life-threatening and/or genitourinary tract infections, hypoglycemia, and ketoacidosis. CONCLUSIONS: EMPOAF will prospectively evaluate whether empagliflozin 10 mg daily can reduce the rate of POAF in patients undergoing elective CABG. Enrolment into this study has started by November 2023 and is expected to be ended before the end of 2025.

Anti-Acinetobacter Baumannii single-chain variable fragments provide therapeutic efficacy in an immunocompromised mouse pneumonia model.

BACKGROUND: The emergence of carbapenem-resistant and extensively drug-resistant (XDR) Acinetobacter baumannii as well as inadequate effective antibiotics calls for an urgent effort to find new antibacterial agents. The therapeutic efficacy of two human scFvs, EB211 and EB279, showing growth inhibitory activity against A. baumannii in vitro, was investigated in immunocompromised mice with A. baumannii pneumonia. RESULTS: The data revealed that infected mice treated with EB211, EB279, and a combination of the two scFvs showed better survival, reduced bacterial load in the lungs, and no marked pathological abnormalities in the kidneys, liver, and lungs when compared to the control groups receiving normal saline or an irrelevant scFv. CONCLUSIONS: The results from this study suggest that the scFvs with direct growth inhibitory activity could offer promising results in the treatment of pneumonia caused by XDR A. baumannii.

In-vitro cytotoxic potential of aerial parts of Leutea avicennae Mozaff. in different Human cancer cell lines.

Medicinal plants such as Leutea avicennae Mozaff. (Apiaceae) have been shown some biological potential for preventing and treating diseases. Fractions and isolated compounds were tested on colon carcinoma (HT-29), cervical carcinoma (HeLa), breast carcinoma (MCF-7), and mouse embryonic fibroblast (NIH/3T3) cell lines. The BSLT method was used for the assessment of the general toxicity of the petroleum ether (PET), chloroform (CHCl3), ethyl acetate (EtOAc), and methanol (MeOH) fractions obtained from the aerial parts of L. avicennae. 1H-NMR and 13 C-NMR spectroscopy were used for structure elucidation. Five compounds, including two coumarins, osthole and umbelliferone, a diterpene phytol, ß-sitosterol, and lauric acid, were isolated for the first time from L. avicennae. Osthole showed potent cytotoxic activity against MCF-7 and HT-29 cell lines with IC50 values of 4.23 ± 0.26 and 12.11 ± 0.13 µg/mL, respectively. Phytol demonstrated potent cytotoxic activity towards MCF-7 and HeLa cell lines with IC50 values of 6.80 ± 0.08 and 12.27 ± 0.18 µg/mL, respectively.

Effects of Sitagliptin as Monotherapy and Add-On to Metformin on Weight Loss among Overweight and Obese Patients with Type 2 Diabetes: A Systematic Review and Meta-Analysis.

BACKGROUND: Sitagliptin is known as an antidiabetic agent inhibiting the dipeptidyl peptidase-4. Although sitagliptin may influence weight, controversial results have been reported, and there is no general agreement on this issue. Therefore, this study assessed the effect of sitagliptin as monotherapy and add-on therapy to metformin on weight reduction in overweight or obese cases with type 2 diabetes. METHODS: We reviewed the following databases to identify all relevant papers published until 1st April 2021: Web of Science, MEDLINE, Embase, Scopus, Cochrane Central Register of Controlled Trials Cochrane Library, and Google Scholar. The research included all clinical trials investigating the effect of sitagliptin in obese or overweight adult patients with type 2 diabetes without any language restriction. RESULTS: In total, eighteen randomized controlled trials with 2009 participants were included in our meta-analysis. Results showed supplementation of sitagliptin has led to weight loss for sitagliptin treated (MD -0.99; 95% CI; (-1.87, -0.12); p=0.026)) and sitagliptin+metformin treated groups (MD -1.09; 95% CI; (-1.69, -0.49); p<0.001)). Also, the intervention has influenced body mass index in sitagliptin treated (MD -0.23; 95% CI; (-0.45, 0.02); p=0.033)) and sitagliptin+metformin treated groups (MD -0.52; 95% CI; (-0.96, 0.08); p=0.020)) comparing to placebo. CONCLUSION: Our results demonstrated that sitagliptin administration with or without metformin might reduce the body weight and body mass index if these drugs are taken for more than 6 months.

A Review of Therapeutic Antibodies in Breast Cancer.

Since the first production of monoclonal antibodies about 35 years ago, researchers have found them useful in the treatment and diagnosis of various diseases such as cancer. By developing different types of monoclonal antibodies such as humanized, drug conjugated, or bispecific ones, researchers, have achieved remarkable success in treating several complicated and challenging diseases, targeting specific antigens or receptors makes monoclonal antibodies the right choice to inhibit signaling pathways like programmed death-ligand 1 (PD-L1) or programmed death1 (PD-1) and changing cell behavior. As one of the most common types of malignancies among women, breast cancer is one of the most critical conditions which different types of monoclonal antibodies were designed and produced to treat. Therefore, we reviewed these antibodies in breast cancer, their targets, and their efficacy and toxicity, with more focus on recent PD-L1or PD-1 inhibitor antibodies in breast cancer and beyond.

A review of potential suggested drugs for coronavirus disease (COVID-19) treatment.

The latest pandemic, coronavirus disease-2019 (COVID-19), is associated with high prevalence and easy transmission, which is expanding globally with no conventional treatment or vaccine. The new virus revealed 79% and 50% genomic similarities with severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV), respectively. Accordingly, since the disease resists testing and adopting new therapeutics, repositioning pre-existing drugs may present a fast and attractive strategy with known safety, characteristics, and dosage used. However, they are not specific and targeted. Therefore, several drugs have been investigated for their efficacy and safety in the treatment of COVID-19; most of them are undergoing clinical trials. This article summarizes clinical investigations of potential therapeutic drugs used as COVID-19 therapy. Subsequently, it prepares a pattern of results and therapeutic targets to help further experiment designs. We have investigated drugs as classified in the following three groups; 1) The drugs which computationally showed effectiveness (in silico) but needed further lab confirmations; 2) Emetine, Teicoplanin, and Nelfinavir have shown effectiveness in vitro; 3) The drugs currently under clinical trial.

The Effect of Curcumin on some of Traditional and Non-traditional Cardiovascular Risk Factors: A Pilot Randomized, Double-blind, Placebo-controlled Trial.

Numerous interventional studies in clinical and preclinical setting stated that intake of curcumin may provide protection against cardiovascular disease. The aim of this trial was investigation of curcumin efficiency on some cardiovascular risk factors in patients with coronary artery disease (CAD). A total of 33 patients with CAD who fulfilled inclusion and exclusion criteria were entered the study. Patients were randomly assigned to receive curcumin or placebo, 500 mg capsules, four times daily for 8 weeks. Lipid profile, blood glucose and high sensitive C-reactive protein (hs-CRP) levels were analyzed at baseline and two months after treatment. Serum levels of triglycerides (P=0.01), LDL-cholesterol (P=0.03) and VLDL-cholesterol (P=0.04) significantly decreased in the curcumin group compared to baseline, without significant changes in total cholesterol, HDL-cholesterol, blood glucose and hs-CRP levels. In all mentioned laboratory parameters, significant difference was not detected between curcumin and placebo. Although curcumin improved some of lipid profile components, it did not show appreciable effect on inflammatory markers in patients with CAD. Therefore, more detailed assessment of metabolic effects or anti-inflammatory activities of curcumin need to perform by extensive human study.

Evaluation of clinical pharmacist's interventions in an infectious diseases ward and impact on patient's direct medication cost.

BACKGROUND: A clinical pharmacist is a key member of the antimicrobial multidisciplinary team involved in patients' pharmacotherapy monitoring. The aim of this study was to determine the frequency and type of medication errors, the type of clinical pharmacy interventions, acceptance of pharmacist interventions by health-care provider team, nursing staff satisfaction with clinical pharmacy services, and the probable impact of clinical pharmacy interventions on decreasing direct medication costs at an infectious diseases ward in Iran. METHODS: All clinical pharmacist interventions such as preventing medication errors were recorded in a previously designed pharmacotherapy monitoring forms. Direct medication cost of patients admitted during the study period was compared with that of subjects hospitalized at the same ward during the year before the intervention period to determine the impact of clinical pharmacy interventions on direct medication costs. RESULTS: The 3 most frequent medication error types were incorrect dose (35.5%), omission error (24.3%), and incorrect medication (14.3%). The mean number of clinical pharmacist intervention per patient was 3.2. Forty percent of clinical pharmacists' interventions are moderate to major clinical significant. Thirty nine percent of clinical pharmacist's interventions had moderate to major financial benefits in present study. The direct medication cost per patient was decreased about 3.8% following clinical pharmacist's interventions. CONCLUSION: Our data demonstrated that incorrect dose was the most frequent medication error in the infectious diseases ward. Major portion of clinical pharmacist interventions were accepted by physicians and nursing staff. Clinical pharmacist interventions non-significantly decreased the direct medication cost of patients.