Vaccine breakthrough hypoxemic COVID-19 pneumonia in patients with auto-Abs neutralizing type I IFNs

Life-threatening `breakthrough' cases of critical COVID-19 are attributed to poor or waning antibody response to the SARS- CoV-2 vaccine in individuals already at risk. Pre-existing autoantibodies (auto-Abs) neutralizing type I IFNs underlie at least 15% of critical COVID-19 pneumonia cases in unvaccinated individuals; however, their contribution to hypoxemic breakthrough cases in vaccinated people remains unknown. Here, we studied a cohort of 48 individuals ( age 20-86 years) who received 2 doses of an mRNA vaccine and developed a breakthrough infection with hypoxemic COVID-19 pneumonia 2 weeks to 4 months later. Antibody levels to the vaccine, neutralization of the virus, and auto- Abs to type I IFNs were measured in the plasma. Forty-two individuals had no known deficiency of B cell immunity and a normal antibody response to the vaccine. Among them, ten (24%) had auto-Abs neutralizing type I IFNs (aged 43-86 years). Eight of these ten patients had auto-Abs neutralizing both IFN-a2 and IFN-., while two neutralized IFN-omega only. No patient neutralized IFN-ss. Seven neutralized 10 ng/mL of type I IFNs, and three 100 pg/mL only. Seven patients neutralized SARS-CoV-2 D614G and the Delta variant (B.1.617.2) efficiently, while one patient neutralized Delta slightly less efficiently. Two of the three patients neutralizing only 100 pg/mL of type I IFNs neutralized both D61G and Delta less efficiently. Despite two mRNA vaccine inoculations and the presence of circulating antibodies capable of neutralizing SARS-CoV-2, auto-Abs neutralizing type I IFNs may underlie a significant proportion of hypoxemic COVID-19 pneumonia cases, highlighting the importance of this particularly vulnerable population

CT ventilation functional image-based IMRT treatment plans are comparable to SPECT ventilation functional image-based plans.

PurposeTo investigate the hypothesis that CT ventilation functional image-based IMRT plans designed to avoid irradiating highly-functional lung regions are comparable to single-photon emission CT (SPECT) ventilation functional image-based plans.Methods and materialsThree IMRT plans were created for eight thoracic cancer patients using: (1) CT ventilation functional images, (2) SPECT ventilation functional images, and (3) anatomic images (no functional images). CT ventilation images were created by deformable image registration of 4D-CT image data sets and quantitative analysis. The resulting plans were analyzed for the relationship between the deviations of CT-functional plan metrics from anatomic plan metrics (ΔCT-anatomic) and those of SPECT-functional plans (ΔSPECT-anatomic), and moreover for agreements of various metrics between the CT-functional and SPECT-functional plans.ResultsThe relationship between ΔCT-anatomic and ΔSPECT-anatomic was strong (e.g., R=0.94; linear regression slope 0.71). The average differences and 95% limits of agreement between the CT-functional and SPECT-functional plan metrics (except for monitor units) for various structures were mostly less than 1% and 2%, respectively.ConclusionsThis study demonstrated a reasonable agreement between the CT ventilation functional image-based IMRT plans and SPECT-functional plans, suggesting the potential for CT ventilation imaging to serve as a surrogate for SPECT ventilation in functional image-guided radiotherapy

CT ventilation functional image-based IMRT treatment plans are comparable to SPECT ventilation functional image-based plans.

PurposeTo investigate the hypothesis that CT ventilation functional image-based IMRT plans designed to avoid irradiating highly-functional lung regions are comparable to single-photon emission CT (SPECT) ventilation functional image-based plans.Methods and materialsThree IMRT plans were created for eight thoracic cancer patients using: (1) CT ventilation functional images, (2) SPECT ventilation functional images, and (3) anatomic images (no functional images). CT ventilation images were created by deformable image registration of 4D-CT image data sets and quantitative analysis. The resulting plans were analyzed for the relationship between the deviations of CT-functional plan metrics from anatomic plan metrics (ΔCT-anatomic) and those of SPECT-functional plans (ΔSPECT-anatomic), and moreover for agreements of various metrics between the CT-functional and SPECT-functional plans.ResultsThe relationship between ΔCT-anatomic and ΔSPECT-anatomic was strong (e.g., R=0.94; linear regression slope 0.71). The average differences and 95% limits of agreement between the CT-functional and SPECT-functional plan metrics (except for monitor units) for various structures were mostly less than 1% and 2%, respectively.ConclusionsThis study demonstrated a reasonable agreement between the CT ventilation functional image-based IMRT plans and SPECT-functional plans, suggesting the potential for CT ventilation imaging to serve as a surrogate for SPECT ventilation in functional image-guided radiotherapy

A Fully-Digital BIST Wrapper Based on Ternary Test Stimuli for the Dynamic Test of a 40 nm CMOS 18-bit Stereo Audio ΣΔ ADC

International audienc

Probabilistic treatment planning for pancreatic cancer treatment : prospective incorporation of respiratory motion shows only limited dosimetric benefit

BACKGROUND: We introduced a probabilistic treatment planning approach that prospectively incorporates respiratory-induced motion in the treatment plan optimization. The aim of this study was to determine the potential dosimetric benefit by comparing this approach to the use of an internal target volume (ITV). MATERIAL AND METHOD: We retrospectively compared the probabilistic respiratory motion-incorporated (RMI) approach to the ITV approach for 18 pancreatic cancer patients, for seven simulated respiratory amplitudes from 5 to 50 mm in the superior-inferior (SI) direction. For each plan, we assessed the target coverage (required: D98%≥95% of 50 Gy prescribed dose). For the RMI plans, we investigated whether target coverage was robust against daily variations in respiratory amplitude. We determined the distance between the clinical target volume and the 30 Gy isodose line (i.e. dose gradient steepness) in the SI direction. To investigate the clinical benefit of the RMI approach, we created for each patient an ITV and RMI treatment plan for the three-dimensional (3D) respiratory amplitudes observed on their pretreatment 4D computed tomography (4DCT). We determined Dmean, V30Gy, V40Gy and V50Gy for the duodenum. RESULTS: All treatment plans yielded good target coverage. The RMI plans were robust against respiratory amplitude variations up to 10 mm, as D98% remained ≥95%. We observed steeper dose gradients compared to the ITV approach, with a mean decrease from 25.9 to 19.2 mm for a motion amplitude of 50 mm. For the 4DCT motion amplitudes, the RMI approach resulted in a mean decrease of 0.43 Gy, 1.1 cm(3), 1.4 cm(3) and 0.9 cm(3) for the Dmean, V30Gy, V40Gy and V50Gy of the duodenum, respectively. CONCLUSION: The probabilistic treatment planning approach yielded significantly steeper dose gradients and therefore significantly lower dose to surrounding healthy tissues than the ITV approach. However, the observed dosimetric gain for clinically observed respiratory motion amplitudes for this patient group was limited

Automated drug dispensing system reduces medication errors in an intensive care setting

International audienceOBJECTIVES:We aimed to assess the impact of an automated dispensing system on the incidence of medication errors related to picking, preparation, and administration of drugs in a medical intensive care unit. We also evaluated the clinical significance of such errors and user satisfaction.DESIGN:Preintervention and postintervention study involving a control and an intervention medical intensive care unit.SETTING:Two medical intensive care units in the same department of a 2,000-bed university hospital.PATIENTS:Adult medical intensive care patients.INTERVENTIONS:After a 2-month observation period, we implemented an automated dispensing system in one of the units (study unit) chosen randomly, with the other unit being the control.MEASUREMENTS AND MAIN RESULTS:The overall error rate was expressed as a percentage of total opportunities for error. The severity of errors was classified according to National Coordinating Council for Medication Error Reporting and Prevention categories by an expert committee. User satisfaction was assessed through self-administered questionnaires completed by nurses. A total of 1,476 medications for 115 patients were observed. After automated dispensing system implementation, we observed a reduced percentage of total opportunities for error in the study compared to the control unit (13.5% and 18.6%, respectively; p<.05); however, no significant difference was observed before automated dispensing system implementation (20.4% and 19.3%, respectively; not significant). Before-and-after comparisons in the study unit also showed a significantly reduced percentage of total opportunities for error (20.4% and 13.5%; p<.01). An analysis of detailed opportunities for error showed a significant impact of the automated dispensing system in reducing preparation errors (p<.05). Most errors caused no harm (National Coordinating Council for Medication Error Reporting and Prevention category C). The automated dispensing system did not reduce errors causing harm. Finally, the mean for working conditions improved from 1.0±0.8 to 2.5±0.8 on the four-point Likert scale.CONCLUSIONS:The implementation of an automated dispensing system reduced overall medication errors related to picking, preparation, and administration of drugs in the intensive care unit. Furthermore, most nurses favored the new drug dispensation organization

Mont’Prospect2.0: Prospecter les montagnes autrement

International audienc

Probabilistic treatment planning for pancreatic cancer treatment: prospective incorporation of respiratory motion shows only limited dosimetric benefit

<p><b>Background:</b> We introduced a probabilistic treatment planning approach that prospectively incorporates respiratory-induced motion in the treatment plan optimization. The aim of this study was to determine the potential dosimetric benefit by comparing this approach to the use of an internal target volume (ITV).</p> <p><b>Material and method:</b> We retrospectively compared the probabilistic respiratory motion-incorporated (RMI) approach to the ITV approach for 18 pancreatic cancer patients, for seven simulated respiratory amplitudes from 5 to 50 mm in the superior-inferior (SI) direction. For each plan, we assessed the target coverage (required: D_98%≥95% of 50 Gy prescribed dose). For the RMI plans, we investigated whether target coverage was robust against daily variations in respiratory amplitude. We determined the distance between the clinical target volume and the 30 Gy isodose line (i.e. dose gradient steepness) in the SI direction. To investigate the clinical benefit of the RMI approach, we created for each patient an ITV and RMI treatment plan for the three-dimensional (3D) respiratory amplitudes observed on their pretreatment 4D computed tomography (4DCT). We determined D_mean, V_30Gy, V_40Gy and V_50Gy for the duodenum.</p> <p><b>Results:</b> All treatment plans yielded good target coverage. The RMI plans were robust against respiratory amplitude variations up to 10 mm, as D_98% remained ≥95%. We observed steeper dose gradients compared to the ITV approach, with a mean decrease from 25.9 to 19.2 mm for a motion amplitude of 50 mm. For the 4DCT motion amplitudes, the RMI approach resulted in a mean decrease of 0.43 Gy, 1.1 cm³, 1.4 cm³ and 0.9 cm³ for the D_mean, V_30Gy, V_40Gy and V_50Gy of the duodenum, respectively.</p> <p><b>Conclusion:</b> The probabilistic treatment planning approach yielded significantly steeper dose gradients and therefore significantly lower dose to surrounding healthy tissues than the ITV approach. However, the observed dosimetric gain for clinically observed respiratory motion amplitudes for this patient group was limited.</p