Efficacy and safety of direct oral anticoagulants in the pediatric population: a systematic review and a meta-analysis.

BACKGROUND: Direct oral anticoagulants (DOACs) represent a cornerstone of adult venous thromboembolism (VTE) treatment. Recently, randomized controlled trials (RCTs) investigating DOACs in pediatrics have been performed. OBJECTIVES: To evaluate the efficacy and safety of DOACs in the pediatric population. METHODS: We systematically searched MEDLINE (PubMed), EMBASE, and ClinicalTrials.gov from initiation up to August 20, 2022, for RCTs comparing DOACs to standard of care (SOC) in patients aged <18 years according to PRISMA guidelines (PROSPERO registration CRD42022353870). The primary analysis was performed according to the anticoagulation intensity and clinical setting (ie, prophylaxis in cardiac disease or treatment in VTE). Efficacy outcomes were all-cause mortality and VTE. Safety outcomes were major bleeding (MB), clinically relevant non-MB, any bleeding, serious adverse events, and discontinuation due to adverse events (AEs). RESULTS: Seven RCTs were included in the systematic review and 6 in the meta-analysis (3 prophylaxis in cardiac disease and 3 treatment in VTE). DOACs showed a significant reduction of VTE recurrence for treatment (odds ratio [OR] = 0.42; 95% CI, 0.19-0.94) and a nonsignificant reduction in VTE occurrence in prophylaxis (OR = 0.22; 95% CI, 0.03-1.55). No differences were observed for any bleeding, serious AEs, and MB in prophylaxis. Nonsignificant trends were observed for clinically relevant non-MB, MB in treatment, and discontinuation due to AE in prophylaxis. We found a significant increase in discontinuation due to AE in treatment. CONCLUSIONS: DOAC treatment seems to reduce VTE compared with SOC without major safety issues in the pediatric population, whereas DOAC prophylaxis seems at least comparable to SOC.

Exploiting Lipid and Polymer Nanocarriers to Improve the Anticancer Sonodynamic Activity of Chlorophyll.

Sonodynamic therapy is an emerging approach that uses low-intensity ultrasound to activate a sonosensitizer agent triggering its cytotoxicity for selective cancer cell killing. Several molecules have been proposed as sonosensitizer agents, but most of these, as chlorophyll, are strongly hydrophobic with a low selectivity towards cancer tissues. Nanocarriers can help to deliver more efficiently the sonosensitizer agents in the target tumor site, increasing at the same time their sonodynamic effect, since nanosystems act as cavitation nuclei. Herein, we propose the incorporation of unmodified plant-extracted chlorophyll into nanocarriers with different composition and structure (i.e., liposomes, solid lipid nanoparticles and poly(lactic-co-glycolic acid) nanoparticles) to obtain aqueous formulations of this natural pigment. The nanocarriers have been deeply characterized and then incubated with human prostatic cancer cells (PC-3) and spheroids (DU-145) to assess the influence of the different formulations on the chlorophyll sonodynamic effect. The highest sonodynamic cytotoxicity was obtained with chlorophyll loaded into poly(lactic-co-glycolic acid) nanoparticles, showing promising results for future clinical investigations on sonodynamic therapy.

SWCNT-porphyrin nano-hybrids selectively activated by ultrasound: an interesting model for sonodynamic applications.

Sonodynamic therapy (SDT) is an innovative anticancer approach, based on the excitation of a given molecule (usually a porphyrin) by inertial acoustic cavitation that leads to cell death via the production of reactive oxygen species (ROS). This study aims to prepare and characterize nanosystems based on porphyrin grafted carbon nanotubes (SWCNTs), to understand some aspects of the mechanisms behind the SDT phenomenon. Three different porphyrins have been covalently linked to SWCNTs using either Diels-Alder or 1,3-dipolar cycloadditions. ROS production and cell viability have been evaluated upon ultrasound irradiation. Despite the low porphyrin content linked on the SWCNT, these systems have shown high ROS production and high tumour-cell-killing ability. The existence of a PET (photoinduced electron transfer)-like process would appear to be able to explain these observations. Moreover, the demonstrated ability to absorb light limits the impact of side effects due to light-excitation.

Porphyrin-Loaded Pluronic Nanobubbles: A New US-Activated Agent for Future Theranostic Applications.

Sonodynamic therapy (SDT) has become a promising noninvasive approach for cancer therapy. The treatment exploits the ability of particular molecules (i.e., porphyrins) to be excited by ultrasound and produce reactive oxygen species (ROS) during their decay process. These reactive species, in turn, result in cell death. To capitalize on the real-time visualization and on-demand delivery of ultrasound contrast agents, this study aims to combine porphyrins with nanobubbles (NBs) to obtain an ultrasound-activated theranostic agent that exploits the SDT activity in vitro. Two porphyrin classes, exposing different hydrophobic side chains, were synthesized. NB size and encapsulation efficiency were markedly dependent on the porphyrin structure. The combination of these porphyrin and NBs resulted in a significant reduction in cell viability upon sonication in pilot studies performed on the LS 174T colorectal cancer cell line.

Microwave-Assisted Synthesis and Physicochemical Characterization of Tetrafuranylporphyrin-Grafted Reduced-Graphene Oxide.

This work describes the design of a modified porphyrin that bears four furan rings linked by 1,2-bis-(2-aminoethoxy)ethane spacers. This unit is a well-suited scaffold for a Diels-Alder reaction with commercial reduced-graphene oxide, which is also described in this paper. A new hybrid material is obtained, thanks to efficient grafting under microwave irradiation, and fully characterized in terms of structure (UV, TGA, Raman) and morphology (HR-TEM and AFM). Potential applications in photo- and sonodynamic therapy are envisaged.