Safety and effectiveness of rituximab in patients with rheumatoid arthritis following an inadequate response to 1 prior tumor necrosis factor inhibitor: the RESET Trial.

OBJECTIVE: To evaluate the safety and effectiveness of rituximab (RTX) in combination with methotrexate in patients with active rheumatoid arthritis (RA) after failure of a single tumor necrosis factor-α (TNF-α) inhibitor. Changes in patient-reported outcomes after primary treatment or retreatment with RTX and factors determining retreatment in clinical practice were also evaluated. METHODS: In this phase 3b open-label, multicenter trial, patients received 2 slow infusions of RTX 1000 mg 14 days apart after premedication (primary treatment). Patients with a clinically relevant response could receive retreatment between 24 and 48 weeks. The primary endpoint was evaluation of safety. Secondary outcomes were safety of retreatment, effectiveness of primary treatment and retreatment, and changes in patient-reported outcomes after primary treatment or retreatment. RESULTS: Of 120 patients enrolled at 36 centers and receiving primary RTX treatment, 77 received retreatment, 112 completed the 24-week primary treatment period, and 25 completed the 48-week primary treatment and retreatment period following a single course of RTX. The most common adverse events were mild to moderate nausea, vomiting, nasopharyngitis, and headache. No infections or infusion reactions were considered life-threatening. At 24 weeks, 58%, 27%, and 7% of patients achieved American College of Rheumatology 20, 50, and 70 improvements, respectively, and similar improvements were seen after retreatment. CONCLUSION: RTX was well tolerated, with a low incidence of infusion reactions and infections. Efficacy results, including enhanced response in rheumatoid factor-positive patients, were comparable to those reported in the literature. Based on its efficacy and safety profile and retreatment schedule, RTX is an attractive treatment option for patients that have not responded to a single TNF-α inhibitor.

Hemodynamic physiology and thermoregulation in liposuction.

Little is known about the physiology of large-volume liposuction. Patients are exposed to prolonged procedures, general anesthesia, fluid shifts, and infusion of high doses of epinephrine and lidocaine. Consequently, the authors examined the thermoregulatory and cardiovascular responses to liposuction by assessing multiple physiologic factors. The aims of their study were to serially determine hemodynamic parameters perioperatively, to quantify perioperative and postoperative plasma epinephrine levels, and to chronologically document fluctuations in core body temperature. Five female volunteers with American Society of Anesthesiologists' physical status I and II underwent moderate- to large-volume liposuction. Heart rate, blood pressure, mean pulmonary arterial pressure, cardiac index, and central venous pressure were monitored. Serum epinephrine levels and core body temperature were assessed perioperatively. The hemodynamic responses to liposuction were characterized by an increase in cardiac index (57 percent), heart rate (47 percent), and mean pulmonary arterial pressure (44 percent) (p < 0.05). Central venous pressure was not significantly altered. Maximum epinephrine levels were observed 5 to 6 hours after induction. Significant correlations between cardiac index and epinephrine concentrations were shown intraoperatively (r = 0.75). All patients developed intraoperative low body temperatures (mean 35.5 degrees C). An overall enhanced cardiac function was observed in patients subsequent to large-volume liposuction. The etiology of the altered cardiac parameters was multifactorial but may have been attributable in part to the administration of epinephrine, which counters the effects of general anesthesia and operative hypothermia. Additional explanations for raised cardiac output may be hemodilution or emergence from general anesthesia. Elevated mean pulmonary arterial pressure may be a result of subclinical fat embolism demonstrated in previous porcine studies, although fat was not observed in urine. The unchanged central venous pressure levels indicate that young healthy patients with compliant right ventricles can accommodate the fluid loads of large-volume liposuction. Overall hemodynamic parameters remained within safe limits. Within these surgical parameters, patients should be clinically screened for cardiovascular and blood pressure disorders before liposuction is undertaken, and preventative measures should be taken to limit intraoperative hypothermia.

A practical approach to a comprehensive epicardial and epiaortic echocardiographic examination.

OBJECTIVE: More than a decade before the introduction of intraoperative transesophageal echocardiography (TEE), epicardial echocardiography was already in use as a diagnostic imaging modality to assist cardiac surgeons and anesthesiologists with clinical decision making. Although TEE has since become increasingly more popular, epicardial echocardiography may be the most convenient intraoperative imaging technique when TEE probe placement cannot be performed or is contraindicated. The authors developed a comprehensive examination protocol for the intraoperative interrogation of cardiac structures using an epicardial/epiaortic echocardiographic approach. DESIGN: Retrospective analysis of patient's medical records. SETTING: Single-center academic tertiary care hospital. PARTICIPANTS: Patients undergoing cardiac surgery. INTERVENTIONS: A total of 10 echocardiographic views were obtained for imaging cardiac structures, the ascending aorta, and proximal aortic arch. The described imaging planes permit the evaluation of ventricular performance, valvular function, cardiac structural abnormalities, and aortic disease. MEASUREMENTS AND MAIN RESULTS: A comprehensive epicardial/epiaortic echocardiographic examination was performed in 20 patients undergoing cardiac surgery requiring a full sternotomy. The described imaging planes were obtained in all patients in less than 8 minutes (range, 3.5-8 minutes; mean, 5.5 minutes). CONCLUSION: The present manuscript delineates a protocol for performing a comprehensive, intraoperative epicardial/epiaortic echocardiographic examination. Echocardiographic imaging planes of cardiac and aortic anatomy are described. This protocol may be useful for cardiac surgeons and anesthesiologists seeking to use this technique as a cardiac imaging modality that is complementary to TEE.