Design and Synthesis of Topoisomerases-Histone Deacetylase Dual Targeted Quinoline-Bridged Hydroxamates as Anticancer Agents.

The multifactorial nature of cancer requires treatment that involves simultaneous targeting of associated overexpressed proteins and cell signaling pathways, possibly leading to synergistic effects. Herein, we present a systematic study that involves the simultaneous inhibition of human topoisomerases (hTopos) and histone deacetylases (HDACs) by multitargeted quinoline-bridged hydroxamic acid derivatives. These compounds were rationally designed considering pharmacophoric features and catalytic sites of the cross-talk proteins, synthesized, and assessed for their anticancer potential.

FDA Approval Summary: Tovorafenib for Relapsed or Refractory BRAF-altered Pediatric Low-Grade Glioma.

On April 23, 2024, FDA granted accelerated approval to tovorafenib, a type II RAF kinase inhibitor, for the treatment of patients 6 months of age and older with relapsed or refractory pediatric low-grade glioma (pLGG) harboring a BRAF fusion or rearrangement, or BRAF V600 mutation. Efficacy was evaluated in FIREFLY-1 (NCT04775485), a single-arm, open-label, multicenter trial that enrolled patients 6 months to 25 years of age with relapsed or refractory pLGG with an activating BRAF alteration who had received prior systemic therapy. The major efficacy outcome measure was radiologic overall response rate (ORR), defined as the proportion of patients with complete response, partial response, or minor response as determined by blinded independent central review using Response Assessment in Pediatric Neuro-Oncology (RAPNO) criteria.

Pyrazoline Derivatives: Exploring the Synthesis and Development of New Ligands for Anti-Cancer Therapy.

Pyrazoline is a 5-membered ring that has two adjacent nitrogen. It has gained advanced attention from medical and organic chemists due to very low cytotoxic activities. It is applicable and more applied in research fields and has various pharmacological activities, including cardiovascular, anti-tumor, and anti-cancer properties.

Freeze-dried plasma: Hemostasis and biophysical analyses for damage control resuscitation.

Background: Effective hemorrhage protocols prioritize immediate hemostatic resuscitation to manage hemorrhagic shock. Prehospital resuscitation using blood products, such as whole blood or alternatively dried plasma in its absence, has the potential to improve outcomes in hemorrhagic shock patients. However, integrating blood products into prehospital care poses substantial logistical challenges due to issues with storage, transport, and administration in field environments.

Point-of-care tests, diagnostic uncertainty and antimicrobial stewardship in the ICU: procalcitonin or PCR to aid antibiotic-stop decisions - an observational cohort study.

Objectives: Intensive care unit (ICU) clinicians stop antibiotics more often, with a negative infection: point-of-care test (PCR-POCT). Simulated cases of diagnostic uncertainty regarding infection resolution led clinicians to choose options such as procalcitonin (PCT) and/or PCR-POCTs +/- de-escalation to aid stop decisions. We hypothesised that a direct infection indicator, PCR-POCT, would influence stop judgements more than indirect PCT.