Use of Erector Spinae Fascial Plane Blocks in Enhanced Recovery for Open Abdominal Surgery.

BACKGROUND: Bilateral erector spinae fascial plane blocks (ESPB) offers a novel, alternative method of regional post-operative pain control to thoracic epidural analgesia (TEA). The aim of this study was to compare rates of postoperative hypotension, and other standard enhanced recovery after surgery (ERAS) endpoints, in patients receiving ESPB versus TEA for open hepatopancreaticobiliary (HPB) surgery. MATERIALS AND METHODS: This retrospective analysis compared historical controls of ERAS patients undergoing open HPB surgery with TEA versus ESPB. The incidence of postoperative hypotension and clinical outcomes, including opioid requirements, were compared. RESULTS: Forty patients receiving TEA were compared to 27 ESPB patients. Return of bowel function and length of stay (mean 7.2 versus7.4 days; P = 0.83) were similar. ESPB patients received less intraoperative colloid (142cc versus 340cc; P = 0.01) and had less postoperative hypotension versus TEA (22% versus 55%; P = 0.03). No ESPB patient required patient-controlled analgesia (versus 32.5% TEA; P< 0.001). ESPB MME requirements decreased over time, while TEA MME requirements increased over 72 hours (P = 0.019). CONCLUSIONS: ESPB is a novel method that shows promising outcomes in improving enhanced recovery parameters and minimizing opioid administration in open HPB surgery.

Mapping the malaria parasite druggable genome by using in vitro evolution and chemogenomics.

Chemogenetic characterization through in vitro evolution combined with whole-genome analysis can identify antimalarial drug targets and drug-resistance genes. We performed a genome analysis of 262 Plasmodium falciparum parasites resistant to 37 diverse compounds. We found 159 gene amplifications and 148 nonsynonymous changes in 83 genes associated with drug-resistance acquisition, where gene amplifications contributed to one-third of resistance acquisition events. Beyond confirming previously identified multidrug-resistance mechanisms, we discovered hitherto unrecognized drug target-inhibitor pairs, including thymidylate synthase and a benzoquinazolinone, farnesyltransferase and a pyrimidinedione, and a dipeptidylpeptidase and an arylurea. This exploration of the P. falciparum resistome and druggable genome will likely guide drug discovery and structural biology efforts, while also advancing our understanding of resistance mechanisms available to the malaria parasite.

Mutations in the P-type cation-transporter ATPase 4, PfATP4, mediate resistance to both aminopyrazole and spiroindolone antimalarials.

Aminopyrazoles are a new class of antimalarial compounds identified in a cellular antiparasitic screen with potent activity against Plasmodium falciparum asexual and sexual stage parasites. To investigate their unknown mechanism of action and thus identify their target, we cultured parasites in the presence of a representative member of the aminopyrazole series, GNF-Pf4492, to select for resistance. Whole genome sequencing of three resistant lines showed that each had acquired independent mutations in a P-type cation-transporter ATPase, PfATP4 (PF3D7_1211900), a protein implicated as the novel Plasmodium spp. target of another, structurally unrelated, class of antimalarials called the spiroindolones and characterized as an important sodium transporter of the cell. Similarly to the spiroindolones, GNF-Pf4492 blocks parasite transmission to mosquitoes and disrupts intracellular sodium homeostasis. Our data demonstrate that PfATP4 plays a critical role in cellular processes, can be inhibited by two distinct antimalarial pharmacophores, and supports the recent observations that PfATP4 is a critical antimalarial target.