Anesthetic evaluation and management of a patient with thoracic endometriosis syndrome presenting for elective surgery

Thoracic endometriosis syndrome is a relatively uncommon disorder characterized by recurrent pneumothoraces, hemothorax, chest pain, dyspnea, and hemoptysis within 48 to 72 hours of menstruation. A 34 year old, ASA physical status 2 woman with recurrent catamenial pneumothoraces due to thoracic endometriosis syndrome is presented. After treatment with video-assisted thoracoscopic surgery, she underwent successful elective diagnostic abdominal laparoscopy without incident. The presence of parenchymal injury and damage predisposes these patients to ventilator-induced lung injury. Postponement of surgery until the intermenstrual period, with lung protective ventilation, allows patients with this disease to successfully undergo general anesthesia and surgery.     

Novel Linker Variants of Antileishmanial/Antitubercular 7-Substituted 2-Nitroimidazooxazines Offer Enhanced Solubility

Antitubercular 7-substituted 2-nitroimidazo[2,1-b][1,3]oxazines were previously shown to exhibit potent antileishmanial and antitrypanosomal activities, culminating in a new clinical investigational drug for visceral leishmaniasis (DNDI-0690). To offset development risks, we continued to seek further leads with divergent candidate profiles, especially analogues possessing greater aqueous solubility. Starting from an efficacious monoaryl derivative, replacement of the side chain ether linkage by novel amine, amide, and urea functionality was first explored; the former substitution was well-tolerated in vitro and in vivo but elicited marginal alterations to solubility (except through a less stable benzylamine), whereas the latter groups resulted in significant solubility improvements (up to 53-fold) but an antileishmanial potency reduction of at least 10-fold. Ultimately, we discovered that O-carbamate 66 offered a more optimal balance of increased solubility, suitable metabolic stability, excellent oral bioavailability (100%), and strong in vivo efficacy in a visceral leishmaniasis mouse model (97% parasite load reduction at 25 mg/kg).