NADPH Phagocyte Oxidase Knockout Mice Control Trypanosoma cruzi Proliferation, but Develop Circulatory Collapse and Succumb to Infection

•NO is considered to be a key macrophage-derived cytotoxic effector during Trypanosoma cruzi infection. On the other hand, the microbicidal properties of reactive oxygen species (ROS) are well recognized, but little importance has been attributed to them during in vivo infection with T. cruzi. In order to investigate the role of ROS in T. cruzi infection, mice deficient in NADPH phagocyte oxidase (gp91phox−/− or phox KO) were infected with Y strain of T. cruzi and the course of infection was followed. phox KO mice had similar parasitemia, similar tissue parasitism and similar levels of IFN-γ and TNF in serum and spleen cell culture supernatants, when compared to wild-type controls. However, all phox KO mice succumbed to infection between day 15 and 21 after inoculation with the parasite, while 60% of wild-type mice were alive 50 days after infection. Further investigation demonstrated increased serum levels of nitrite and nitrate (NOx) at day 15 of infection in phox KO animals, associated with a drop in blood pressure. Treatment with a NOS2 inhibitor corrected the blood pressure, implicating NOS2 in this phenomenon. We postulate that superoxide reacts with •NO in vivo, preventing blood pressure drops in wild type mice. Hence, whilst superoxide from phagocytes did not play a critical role in parasite control in the phox KO animals, its production would have an important protective effect against blood pressure decline during infection with T. cruzi

Carbon Dioxide Embolism Associated with Transanal Total Mesorectal Excision Surgery: A Report From the International Registries

BACKGROUND: Carbon dioxide embolus has been reported as a rare but clinically important risk associated with transanal total mesorectal excision surgery. To date, there exists limited data describing the incidence, risk factors, and management of carbon dioxide embolus in transanal total mesorectal excision. OBJECTIVE: This study aimed to obtain data from the transanal total mesorectal excision registries to identify trends and potential risk factors for carbon dioxide embolus specific to this surgical technique. DESIGN: Contributors to both the LOREC and OSTRiCh transanal total mesorectal excision registries were invited to report their incidence of carbon dioxide embolus. Case report forms were collected detailing the patient-specific and technical factors of each event. SETTINGS: The study was conducted at the collaborating centers from the international transanal total mesorectal excision registries. MAIN OUTCOME MEASURES: Characteristics and outcomes of patients with carbon dioxide embolus associated with transanal mesorectal excision were measured. RESULTS: Twenty-five cases were reported. The incidence of carbon dioxide embolus during transanal total mesorectal excision is estimated to be 480.4% (25/6375 cases). A fall in end tidal carbon dioxide was noted as the initial feature in 22 cases, with 13 (52%) developing signs of hemodynamic compromise. All of the events occurred in the transanal component of dissection, with mean (range) insufflation pressures of 15mm Hg (12\u201320mm Hg). Patients were predominantly (68%) in a Trendelenburg position, between 30\ub0 and 45\ub0. Venous bleeding was reported in 20 cases at the time of carbon dioxide embolus, with periprostatic veins documented as the most common site (40%). After carbon dioxide embolus, 84% of cases were completed after hemodynamic stabilization. Two patients required cardiopulmonary resuscitation because of cardiovascular collapse. There were no deaths. LIMITATIONS: This is a retrospective study surveying reported outcomes by surgeons and anesthetists. CONCLUSIONS: Surgeons undertaking transanal total mesorectal excision must be aware of the possibility of carbon dioxide embolus and its potential risk factors, including venous bleeding (wrong plane surgery), high insufflation pressures, and patient positioning. Prompt recognition and management can limit the clinical impact of such events. See Video Abstract at http://links. lww.com/DCR/A961