Update on the efficacy and safety of intravenous tranexamic acid in hip fracture surgery: a systematic review and meta-analysis.

AIM: The aim of this meta-analysis was to assess the safety and efficacy of tranexamic acid (TXA) in the management of hip fracture surgeries in comparison with placebo. METHODS: A systematic search was conducted from August 6, 2021. Eligible studies included randomized clinical trials and prospective studies comparing the use of intravenous TXA in patients treated for hip fractures, in comparison with placebo. Review Manager was used for the meta-analysis. RESULTS: Eighteen prospective studies including 14 RCTs met the eligibility criteria. The results favored the TXA group in the quantity of total blood loss (MD = - 196.91 mL, 95% CI - 247.59, - 146.23, I2 = 92%), intraoperative blood loss (MD = - 26.86 mL, 95% CI - 36.96, - 16.78, I2 = 62%), and rate of blood transfusion (OR 0.35, 95% CI 0.28, 0.42, I2 = 0%). TXA also exhibited higher hemoglobin level at day 1 (MD = 6.77 g/L, 95% CI 4.30, 9.24, I2 = 83%) and day 3 (MD = 7.02 g/L, 95% CI 3.30, 10.74, I2 = 82%) postoperatively. There was no significant difference found in the incidence of thromboembolic events from occurring between the two groups, such as deep vein thrombosis (OR 1.22, 95% CI 0.73, 2.02, I2 = 0%) and pulmonary embolism (OR 0.82, 95% CI 0.33, 2.05, I2 = 0%). CONCLUSION: Administration of intravenous TXA appears to reduce blood loss, rate of blood transfusions and pose no increased risk of thromboembolic events. Therefore, TXA should be considered by physicians when managing hip fracture patients.

Keeping a Balance During the Pandemic: a Narrative Review on the Important Role of Micronutrients in Preventing Infection and Reducing Complications of COVID-19.

PURPOSE OF REVIEW: The SARS-CoV-2 (COVID-19) outbreak has manifested into a major public health concern across the globe, affecting particularly the most vulnerable population groups. Currently, there are various clinical trials being conducted to develop effective treatments. It is estimated that it could take one or more years before these drugs pass all safety tests and concrete results with regard to their effectiveness become available. In addition, despite the recent development of vaccines (licensed for use under conditional licenses) and the commencement of COVID-19 vaccination programs in several countries, there is still a need for safe and novel strategies that may reduce the symptomatology and/or prevent the severe complications associated with COVID-19. Natural compounds previously shown to have antiviral potential should be thoroughly considered and investigated for use in prophylactic treatment of COVID-19 due to their availability and safety. RECENT FINDINGS: The current narrative review investigates whether there is evidence in the literature that supplementation with dietary minerals and vitamins may have a role in preventing infection with SARS-CoV-2 or in reducing COVID-19 symptomatology and disease progression. The current evidence from the literature supports that zinc and vitamin C have a potential in reducing the inflammatory response associated with SARS-CoV-2 while folate and vitamin D may have a role in antagonizing the entry of SARs-CoV-2 virus in host calls. Thus, further research should be conducted that could lead to the development of nutritional supplements involving natural and widely available compounds such as zinc, folate, vitamin C, and vitamin D. The latter could be an effective, safe, and inexpensive way to either prevent infection with SARS-CoV-2 and/or lessen the burden of COVID-19 disease.

Targeting enhancer switching overcomes non-genetic drug resistance in acute myeloid leukaemia.

Non-genetic drug resistance is increasingly recognised in various cancers. Molecular insights into this process are lacking and it is unknown whether stable non-genetic resistance can be overcome. Using single cell RNA-sequencing of paired drug naïve and resistant AML patient samples and cellular barcoding in a unique mouse model of non-genetic resistance, here we demonstrate that transcriptional plasticity drives stable epigenetic resistance. With a CRISPR-Cas9 screen we identify regulators of enhancer function as important modulators of the resistant cell state. We show that inhibition of Lsd1 (Kdm1a) is able to overcome stable epigenetic resistance by facilitating the binding of the pioneer factor, Pu.1 and cofactor, Irf8, to nucleate new enhancers that regulate the expression of key survival genes. This enhancer switching results in the re-distribution of transcriptional co-activators, including Brd4, and provides the opportunity to disable their activity and overcome epigenetic resistance. Together these findings highlight key principles to help counteract non-genetic drug resistance.