Tocilizumab for Severe Worsening COVID-19 Pneumonia: a Propensity Score Analysis.

BACKGROUND: High levels of serum interleukin-6 (IL-6) correlate with disease severity in COVID-19. We hypothesized that tocilizumab (a recombinant humanized anti-IL-6 receptor) could improve outcomes in selected patients with severe worsening COVID-19 pneumonia and high inflammatory parameters. METHODS: The TOCICOVID study included a prospective cohort of patients aged 16-80 years with severe (requiring > 6 L/min of oxygen therapy to obtain Sp02 > 94%) rapidly deteriorating (increase by ≥ 3 L/min of oxygen flow within the previous 12 h) COVID-19 pneumonia with ≥ 5 days of symptoms and C-reactive protein levels > 40 mg/L. They entered a compassionate use program of treatment with intravenous tocilizumab (8 mg/kg with a maximum of 800 mg per infusion; and if needed a second infusion 24 to 72 h later). A control group was retrospectively selected with the same inclusion criteria. Outcomes were assessed at D28 using inverse probability of treatment weighted (IPTW) methodology. RESULTS: Among the 96 patients included (81% male, mean (SD) age: 60 (12.5) years), underlying conditions, baseline disease severity, and concomitant medications were broadly similar between the tocilizumab (n = 49) and the control (n = 47) groups. In the IPTW analysis, treatment with tocilizumab was associated with a reduced need for overall ventilatory support (49 vs. 89%, wHR: 0.39 [0.25-0.56]; p < 0.001). Albeit lacking statistical significance, there was a substantial trend towards a reduction of mechanical ventilation (31% vs. 45%; wHR: 0.58 [0.36-0.94]; p = 0.026). However, tocilizumab did not improve overall survival (wHR = 0.68 [0.31-1.748], p = 0.338). Among the 85 (89%) patients still alive at D28, patients treated with tocilizumab had a higher rate of oxygen withdrawal (82% vs. 73.5%, wHR = 1.66 [1.17-2.37], p = 0.005), with a shorter delay before being weaned of oxygen therapy (mean 11 vs. 16 days; p < 0.001). At D28, the rate of patients discharged from hospital was higher in the tocilizumab group (70% vs. 40%, wHR = 1.82 [1.22-2.75]; p = 0.003). The levels of CRP and fibrinogen post therapy (p < 0.001 for both variables) were significantly lower in the tocilizumab group (interaction test, mixed model). Rates of neutropenia (35% vs. 0%; p < 0.001) were higher in the tocilizumab group, yet rates of infections (22% vs. 38%, p = 0.089) including ventilator-acquired pneumonia (8% vs. 26%, p = 0.022) were higher in the control group. CONCLUSION: These data could be helpful for the design of future trials aiming to counter COVID-19-induced inflammation, especially before patients require admission to the intensive care unit.

Central venous oxygen saturation is not predictive of early complications in cancer patients presenting to the emergency department.

Central venous oxygen saturation (ScvO2) is easily observable in oncology patients with long-term central venous catheters (CVC), and has been studied as a prognostic factor in patients with sepsis. We sought to investigate the association between ScvO2 and early complications in cancer patients presenting to the ED. We prospectively enrolled adult cancer patients with pre-existing CVC who presented to the ED. ScvO2 was measured on their CVC. The outcome was admission to the intensive care unit (ICU) or mortality by day 7. ScvO2 was first studied as a continuous variable (%) with a ROC analysis and as a categorical variable (cut-off at < 70%) with a multivariate analysis. A total of 210 cancer patients were enrolled. At baseline, ScvO2 showed no significant difference between patients who were admitted to the ICU or died before day 7, and patients who did not (67%; IQR 62-68% vs. 71%; IQR 65-78% respectively, P = 0.3). The ROC analysis showed the absence of discrimination accuracy for ScvO2 to predict the outcome (AUC = 0.56). By multivariate analysis, ScvO2 < 70% was not associated with the outcome (OR 1.67; 95% CI 0.64-4.36). Variables that were associated with ICU admission or death by day 7 included a shock-index (heart rate/systolic blood pressure) > 1 and a performance status > 2 (OR 4.76; 95% CI 1.81-12.52 and OR 6.23, 95% CI 2.40-16.17, respectively). This study does not support the use of ScvO2 to risk stratify cancer patients presenting to the ED.

Monitoring Personalized Learning Curves for Emergency Ultrasound With Risk-adjusted Learning-curve Cumulative Summation Method.

BACKGROUND: Ultrasound (US) has been a regular practice in emergency departments for several decades. Thus, train our students to US is of prime interest. Because US image acquisition ability can be very different from a patient to another (depending on image quality), it seems relevant to adapt US learning curves (LCs) to patient image quality using tools based on cumulative summation (CUSUM) as the risk-adjusted LC CUSUM (RLC). OBJECTIVES: The aim of this study was to monitor LC of medical students for the acquisition of abdominal emergency US views and to adapt these curves to patient image quality using RLC. METHODS: We asked medical students to perform abdominal US examinations with the acquisition of 11 views of interest on emergency patients after a learning session. Emergency physicians reviewed the student examinations for validation. LCs were plotted and the student was said proficient for a specific view if his LC reached a predetermined limit fixed by simulation. RESULTS: Seven students with no previous experience in US were enrolled. They performed 19 to 50 examinations of 11 views each. They achieve proficiency for a median of 9 (6-10) views. Aorta and right pleura views were validated by seven students; inferior vena cava, right kidney, and bladder by six; gallbladder and left kidney by five; portal veins and portal hilum by four; and subxyphoid and left pleura by three. The number of US examinations required to reach proficiency ranged from five to 41 depending on the student and on the type of view. LC showed that students reached proficiency with different learning speeds. CONCLUSIONS: This study suggests that, when monitoring LCs for abdominal emergency US, there is some heterogeneity in the learning process depending on the student skills and the type of view. Therefore, rules based on a predetermined number of examinations to reach proficiency are not satisfactory.