Beneficial effect of corticosteroids in preventing mortality in patients receiving tocilizumab to treat severe COVID-19 illness.

OBJECTIVES: To assess the characteristics and risk factors for mortality in patients with severe coronavirus disease-2019 (COVID-19) treated with tocilizumab (TCZ), alone or in combination with corticosteroids (CS). METHODS: From March 17 to April 7, 2020, a real-world observational retrospective analysis of consecutive hospitalized adult patients receiving TCZ to treat severe COVID-19 was conducted at our 750-bed university hospital. The main outcome was all-cause in-hospital mortality. RESULTS: A total of 1,092 patients with COVID-19 were admitted during the study period. Of them, 186 (17%) were treated with TCZ, of which 129 (87.8%) in combination with CS. Of the total 186 patients, 155 (83.3 %) patients were receiving noninvasive ventilation when TCZ was initiated. Mean time from symptoms onset and hospital admission to TCZ use was 12 (±4.3) and 4.3 days (±3.4), respectively. Overall, 147 (79%) survived and 39 (21%) died. By multivariate analysis, mortality was associated with older age (HR = 1.09, p < 0.001), chronic heart failure (HR = 4.4, p = 0.003), and chronic liver disease (HR = 4.69, p = 0.004). The use of CS, in combination with TCZ, was identified as a protective factor against mortality (HR = 0.26, p < 0.001) in such severe COVID-19 patients receiving TCZ. No serious superinfections were observed after a 30-day follow-up. CONCLUSIONS: In patients with severe COVID-19 receiving TCZ due to systemic host-immune inflammatory response syndrome, the use of CS in addition to TCZ therapy, showed a beneficial effect in preventing in-hospital mortality.

Attitude Stabilization of Spacecraft in Very Low Earth Orbit by Center-Of-Mass Shifting.

At very low orbital altitudes (≲450 km) the aerodynamic forces can become major attitude disturbances. Certain missions that would benefit from a very low operational altitude require stable attitudes. The use of internal shifting masses, actively shifting the location of the spacecraft center-of-mass, thus modulating, in direction and magnitude, the aerodynamic torques, is here proposed as a method to reject these aerodynamic disturbances. A reduced one degree-of-freedom model is first used to evaluate the disturbance rejection capabilities of the method with respect to multiple system parameters (shifting mass, shifting range, vehicle size, and altitude). This analysis shows that small shifting masses and limited shifting ranges suffice if the nominal center-of-mass is relatively close to the estimated center-of-pressure. These results are confirmed when the analysis is extended to a full three rotational degrees-of-freedom model. The use of a quaternion feedback controller to detumble a spacecraft operating at very low altitudes is also explored. The analysis and numerical simulations are conducted using a nonlinear dynamic model that includes the full effects of the shifting masses, a realistic atmospheric model, and uncertain spacecraft aerodynamic properties. Finally, a practical implementation on a 3U CubeSat using commercial-off-the-shelf components is briefly presented, demonstrating the implementation feasibility of the proposed method.

Simultaneous Capture and Detumble of a Resident Space Object by a Free-Flying Spacecraft-Manipulator System.

A maneuver to capture and detumble an orbiting space object using a chaser spacecraft equipped with a robotic manipulator is presented. In the proposed maneuver, the capture and detumble objectives are integrated into a unified set of terminal constraints. Terminal constraints on the end-effector's position and velocity ensure a successful capture, and a terminal constraint on the chaser's momenta ensures a post-capture chaser-target system with zero angular momentum. The manipulator motion required to achieve a smooth, impact-free grasp is gradually stopped after capture, equalizing the momenta across all bodies, rigidly connecting the two vehicles, and completing the detumble of the newly formed chaser-target system without further actuation. To guide this maneuver, an optimization-based approach that enforces the capture and detumble terminal constraints, avoids collisions, and satisfies actuation limits is used. The solution to the guidance problem is obtained by solving a collection of convex programming problems, making the proposed guidance approach suitable for onboard implementation and real-time use. This simultaneous capture and detumble maneuver is evaluated through numerical simulations and hardware-in-the-loop experiments. Videos of the numerically simulated and experimentally demonstrated maneuvers are included as Supplementary Material.

Development and validation of a simple high-performance liquid chromatography analytical method for simultaneous determination of phytosterols, cholesterol and squalene in parenteral lipid emulsions.

A simple analytical method for simultaneous determination of phytosterols, cholesterol and squalene in lipid emulsions was developed owing to increased interest in their clinical effects. Method development was based on commonly used stationary (C18 , C8 and phenyl) and mobile phases (mixtures of acetonitrile, methanol and water) under isocratic conditions. Differences in stationary phases resulted in peak overlapping or coelution of different peaks. The best separation of all analyzed compounds was achieved on Zorbax Eclipse XDB C8 (150 × 4.6 mm, 5 µm; Agilent) and ACN-H2 O-MeOH, 80:19.5:0.5 (v/v/v). In order to achieve a shorter time of analysis, the method was further optimized and gradient separation was established. The optimized analytical method was validated and tested for routine use in lipid emulsion analyses.

Outpatient treatment of Pseudomonas aeruginosa bronchial colonization with long-term inhaled colistin, tobramycin, or both in adults without cystic fibrosis.

STUDY OBJECTIVE: To compare clinical and microbiologic outcomes in adults without cystic fibrosis who had Pseudomonas aeruginosa bronchial colonization and were receiving inhaled colistin or colistin plus tobramycin with those who were receiving inhaled tobramycin as outpatient treatment. DESIGN: Prospective, observational cohort study. SETTING: Referral pneumology service at a tertiary university care hospital. PATIENTS: Eighty-one Caucasian adults without cystic fibrosis who received 97 courses of inhaled colistin alone, colistin plus tobramycin, or inhaled tobramycin alone as outpatient treatment of P. aeruginosa bronchial colonization between January 2004 and December 2008. MEASUREMENTS AND MAIN RESULTS: The frequency and duration of hospitalizations for respiratory exacerbations were the primary outcomes compared among treatment groups. Secondary outcomes were emergence of bacterial resistance, antibiotic use during admission, emergence of other opportunistic microorganisms, achievement of sustained P. aeruginosa eradication in the airways, and mortality, as well as safety and changes in respiratory function. No significant differences between colistin and tobramycin were found in the mean number of hospital admissions, duration of hospitalizations, duration of antibiotic treatment, adverse events, mortality, or emergence of other opportunistic microorganisms. Emergence of resistance to colistin was lower than resistance to tobramycin (hazard ratio 0.09, 95% confidence interval [CI] 0.03-0.32). Patients treated with both inhaled antibiotics had fewer days of hospitalization and fewer days of antibiotic use than those treated with tobramycin alone (relative risk [RR] 0.33, 95% CI 0.10-1.12, and RR 0.27, 95% CI 0.08-0.93, respectively). CONCLUSION: Results with colistin were similar to those with tobramycin for inhaled treatment of P. aeruginosa colonization in this population; however, combined use of colistin and tobramycin appeared to be associated with fewer days of hospitalization and shorter duration of antibiotic treatment. Prospective, double-blind, placebo-controlled trials of outpatient nebulized antibiotics, especially colistin plus tobramycin, should be performed to ascertain the efficacy of this therapy for treatment of P. aeruginosa colonization in patients without cystic fibrosis.

Phytosterolemia in parenteral nutrition patients: implications for liver disease development.

OBJECTIVE: Phytosterols present in parenteral nutrition (PN) lipid emulsions have been linked to phytosterolemia and cholestatic liver disease, although no direct relation has been established. We investigated the relation among plasma phytosterol (PY) infused, total plasma PY levels, and possible links to PN-associated liver disease. METHODS: Twenty-seven adult patients on home PN were enrolled in the study. PYs were measured in plasma and lipid emulsions by gas chromatography. Liver function tests and blood counts were assessed to identify hepatic impairment, and biopsies were performed in eight patients. RESULTS: Mean total plasma PY level was higher in patients than in controls (55.4 +/- 6.2 versus 14.8 +/- 2.3 microg/mL). Simple linear regression models showed a correlation among total plasma PY, liver function tests, and platelet counts, which was stronger for total bilirubin (r(2) = 0.53, P = 0.0001) and aspartate aminotransferase (r(2) = 0.50, P = 0.0001) and weaker for platelet counts (r(2) = 0.158, P = 0.04); between infused lipid and liver function tests, the correlation was significant for total bilirubin (r(2) = 0.19, P = 0.038) and aspartate aminotransferase (r(2) = 0.164, P = 0.049). In multiple linear regression analysis, a decreased oral diet (b = -52.3, P = 0.001) and infused PY (b = 2.54, P = 0.093) were risk factors for high plasma PY levels (r(2) = 0.54). Biopsies showed moderate to severe liver impairment in five patients. CONCLUSION: Liver damage may be linked to high plasma PY levels and strengthened by lack of an oral diet in patients on home PN.