A comparison of the effectiveness of different doses of tocilizumab and sarilumab in the treatment of severe COVID-19: a natural experiment due to drug shortages.

OBJECTIVES: Interleukin (IL)-6 inhibitors are administered to treat patients hospitalized with COVID-19. In 2021, due to shortages, different dosing regimens of tocilizumab, and a switch to sarilumab, were consecutively implemented. Using real-world data, we compare the effectiveness of these IL-6 inhibitors. METHODS: Hospitalized patients with COVID-19, treated with IL-6 inhibitors, were included in this natural experiment study. Sixty-day survival, hospital- and intensive care unit (ICU) length of stay, and progression to ICU or death were compared between 8 mg/kg tocilizumab, fixed-dose tocilizumab, low-dose tocilizumab, and fixed-dose sarilumab treatment groups. RESULTS: A total of 5485 patients from 49 hospitals were included. After correction for confounding, increased hazard ratios (HRs) for 60-day mortality were observed for fixed-dose tocilizumab (HR 1.20, 95% confidence interval [CI] 1.04-1.39), low-dose tocilizumab (HR 1.12, 95% CI 0.97-1.31), and sarilumab (HR 1.24, 95% CI 1.08-1.42), all relative to 8 mg/kg. The 8 mg/kg dosing regimen had lower odds of progression to ICU or death. Both hospital- and ICU length of stay were shorter for low-dose tocilizumab than for the 8 mg/kg group. CONCLUSION: We found differences in the probability of 60-day survival and the incidence of the combined outcome of mortality or ICU admission, mostly favoring 8 mg/kg tocilizumab. Because of potential time-associated residual confounding, further clinical studies are warranted.

Development of a CT-Compatible, Anthropomorphic Skull and Brain Phantom for Neurosurgical Planning, Training, and Simulation.

BACKGROUND: Neurosurgical procedures are complex and require years of training and experience. Traditional training on human cadavers is expensive, requires facilities and planning, and raises ethical concerns. Therefore, the use of anthropomorphic phantoms could be an excellent substitute. The aim of the study was to design and develop a patient-specific 3D-skull and brain model with realistic CT-attenuation suitable for conventional and augmented reality (AR)-navigated neurosurgical simulations. METHODS: The radiodensity of materials considered for the skull and brain phantoms were investigated using cone beam CT (CBCT) and compared to the radiodensities of the human skull and brain. The mechanical properties of the materials considered were tested in the laboratory and subsequently evaluated by clinically active neurosurgeons. Optimization of the phantom for the intended purposes was performed in a feedback cycle of tests and improvements. RESULTS: The skull, including a complete representation of the nasal cavity and skull base, was 3D printed using polylactic acid with calcium carbonate. The brain was cast using a mixture of water and coolant, with 4 wt% polyvinyl alcohol and 0.1 wt% barium sulfate, in a mold obtained from segmentation of CBCT and T1 weighted MR images from a cadaver. The experiments revealed that the radiodensities of the skull and brain phantoms were 547 and 38 Hounsfield units (HU), as compared to real skull bone and brain tissues with values of around 1300 and 30 HU, respectively. As for the mechanical properties testing, the brain phantom exhibited a similar elasticity to real brain tissue. The phantom was subsequently evaluated by neurosurgeons in simulations of endonasal skull-base surgery, brain biopsies, and external ventricular drain (EVD) placement and found to fulfill the requirements of a surgical phantom. CONCLUSIONS: A realistic and CT-compatible anthropomorphic head phantom was designed and successfully used for simulated augmented reality-led neurosurgical procedures. The anatomic details of the skull base and brain were realistically reproduced. This phantom can easily be manufactured and used for surgical training at a low cost.

Augmented reality navigation for cranial biopsy and external ventricular drain insertion.

OBJECTIVE: The aim of this study was to evaluate the accuracy (deviation from the target or intended path) and efficacy (insertion time) of an augmented reality surgical navigation (ARSN) system for insertion of biopsy needles and external ventricular drains (EVDs), two common neurosurgical procedures that require high precision. METHODS: The hybrid operating room-based ARSN system, comprising a robotic C-arm with intraoperative cone-beam CT (CBCT) and integrated video tracking of the patient and instruments using nonobtrusive adhesive optical markers, was used. A 3D-printed skull phantom with a realistic gelatinous brain model containing air-filled ventricles and 2-mm spherical biopsy targets was obtained. After initial CBCT acquisition for target registration and planning, ARSN was used for 30 cranial biopsies and 10 EVD insertions. Needle positions were verified by CBCT. RESULTS: The mean accuracy of the biopsy needle insertions (n = 30) was 0.8 mm ± 0.43 mm. The median path length was 39 mm (range 16-104 mm) and did not correlate to accuracy (p = 0.15). The median device insertion time was 149 seconds (range 87-233 seconds). The mean accuracy for the EVD insertions (n = 10) was 2.9 mm ± 0.8 mm at the tip with a 0.7° ± 0.5° angular deviation compared with the planned path, and the median insertion time was 188 seconds (range 135-400 seconds). CONCLUSIONS: This study demonstrated that ARSN can be used for navigation of percutaneous cranial biopsies and EVDs with high accuracy and efficacy.