A Cryptic Case of an Anaerobic Hepatic Abscess Following a Cesarean Section.

Postpartum infectious complications can present with a wide range of nonspecific symptoms. Herein, we describe a complicated late postpartum presentation of recurrent fever following a cesarean delivery complicated by chorioamnionitis. Following discharge, the patient experienced cyclical fever and was treated with antipyretics as an outpatient. The patient continued to experience symptoms and reported to the hospital for further evaluation. Initially thought to be septic pelvic thrombophlebitis, the patient was trialed on clindamycin and gentamycin without resolution of symptoms. After extensive evaluation, the fevers were found to be the result of an infected periuterine hematoma and a concomitant subcapsular inferior hepatic abscess. Bacterial cultures isolated two rare anaerobic organisms: Peptoniphilus ssp. and Finegoldia magna. Source control was achieved by drainage of the two abscesses followed by antibiotic treatment with ertapenem and metronidazole, and the patient recovered successfully. This is the first reported case, to the authors' knowledge, of this complicated postpartum picture due to these anaerobic organisms.

PARP-inhibition reprograms macrophages toward an anti-tumor phenotype.

Poly(ADP)ribosylation inhibitors (PARPis) are toxic to cancer cells with homologous recombination (HR) deficiency but not to HR-proficient cells in the tumor microenvironment (TME), including tumor-associated macrophages (TAMs). As TAMs can promote or inhibit tumor growth, we set out to examine the effects of PARP inhibition on TAMs in BRCA1-related breast cancer (BC). The PARPi olaparib causes reprogramming of TAMs toward higher cytotoxicity and phagocytosis. A PARPi-related surge in NAD+ increases glycolysis, blunts oxidative phosphorylation, and induces reverse mitochondrial electron transport (RET) with an increase in reactive oxygen species (ROS) and transcriptional reprogramming. This reprogramming occurs in the absence or presence of PARP1 or PARP2 and is partially recapitulated by addition of NAD derivative methyl-nicotinamide (MNA). In vivo and ex vivo, the effect of olaparib on TAMs contributes to the anti-tumor efficacy of the PARPi. In vivo blockade of the "don't-eat-me signal" with CD47 antibodies in combination with olaparib improves outcomes in a BRCA1-related BC model.

Intercepted Retro-Nazarov Reaction: Syntheses of Amidino-Rocaglate Derivatives and Their Biological Evaluation as eIF4A Inhibitors.

Rocaglates are a family of natural products isolated from the genus Aglaia which possess a highly substituted cyclopenta[b]benzofuran skeleton and inhibit cap-dependent protein synthesis. Rocaglates are attractive compounds due to their potential for inhibiting tumor cell maintenance in vivo by specifically targeting eukaryotic initiation factor 4A (eIF4A) and interfering with recruitment of ribosomes to mRNA. In this paper, we describe an intercepted retro-Nazarov reaction utilizing intramolecular tosyl migration to generate a reactive oxyallyl cation on the rocaglate skeleton. Trapping of the oxyallyl cation with a diverse range of nucleophiles has been used to generate over 50 novel amidino-rocaglate (ADR) and amino-rocaglate derivatives. Subsequently, these derivatives were evaluated for their ability to inhibit cap-dependent protein synthesis where they were found to outperform previous lead compounds including the rocaglate hydroxamate CR-1-31-B.