Development and external validation of a prediction model for the transition from mild to moderate or severe form of COVID-19.

OBJECTIVES: COVID-19 pandemic seems to be under control. However, despite the vaccines, 5 to 10% of the patients with mild disease develop moderate to critical forms with potential lethal evolution. In addition to assess lung infection spread, chest CT helps to detect complications. Developing a prediction model to identify at-risk patients of worsening from mild COVID-19 combining simple clinical and biological parameters with qualitative or quantitative data using CT would be relevant to organizing optimal patient management. METHODS: Four French hospitals were used for model training and internal validation. External validation was conducted in two independent hospitals. We used easy-to-obtain clinical (age, gender, smoking, symptoms' onset, cardiovascular comorbidities, diabetes, chronic respiratory diseases, immunosuppression) and biological parameters (lymphocytes, CRP) with qualitative or quantitative data (including radiomics) from the initial CT in mild COVID-19 patients. RESULTS: Qualitative CT scan with clinical and biological parameters can predict which patients with an initial mild presentation would develop a moderate to critical form of COVID-19, with a c-index of 0.70 (95% CI 0.63; 0.77). CT scan quantification improved the performance of the prediction up to 0.73 (95% CI 0.67; 0.79) and radiomics up to 0.77 (95% CI 0.71; 0.83). Results were similar in both validation cohorts, considering CT scans with or without injection. CONCLUSION: Adding CT scan quantification or radiomics to simple clinical and biological parameters can better predict which patients with an initial mild COVID-19 would worsen than qualitative analyses alone. This tool could help to the fair use of healthcare resources and to screen patients for potential new drugs to prevent a pejorative evolution of COVID-19. CLINICAL TRIAL REGISTRATION: NCT04481620. CLINICAL RELEVANCE STATEMENT: CT scan quantification or radiomics analysis is superior to qualitative analysis, when used with simple clinical and biological parameters, to determine which patients with an initial mild presentation of COVID-19 would worsen to a moderate to critical form. KEY POINTS: • Qualitative CT scan analyses with simple clinical and biological parameters can predict which patients with an initial mild COVID-19 and respiratory symptoms would worsen with a c-index of 0.70. • Adding CT scan quantification improves the performance of the clinical prediction model to an AUC of 0.73. • Radiomics analyses slightly improve the performance of the model to a c-index of 0.77.

Secreted phospholipase A2 XIIA triggers a mitochondrial damage-induced senescence in chronic obstructive pulmonary disease fibroblasts.

RATIONALE: Lung fibroblast senescence is involved in the pathophysiology of chronic obstructive pulmonary disease (COPD). However, the mechanisms underlining this phenomenon are still poorly understood. Secreted phospholipases (sPLA2, a subclass of phospholipases) are secreted by senescent cells and can in turn induce senescence. However, their role in fibroblasts senescence in COPD is unknown. OBJECTIVES: The aim of this study was to analyze the role of sPLA2 in pulmonary fibroblast senescence. METHODS: Fibroblasts were isolated from patients with COPD and control subjects, and senescence markers and inflammatory profile was analyzed. sPLA2 levels were quantified in serum of COPD and controls. MAIN RESULTS: In comparison with non-smokers and smoker controls, senescent lung COPD fibroblasts exhibited a higher mRNA and protein expression of the sPLA2 isoform XIIA and of syndecan 4 (one of its receptors). sPLA2 XIIA induced in turn senescence of non-senescent pulmonary fibroblasts via a pathway involving consecutively syndecan 4, activation of MAPK and p-serine 727 STAT-3, increased mitochondrial ROS production, and activation of AMPK/p53. This pathway was associated with a specific inflammatory secretome (IL-10, IL-12 and TNFα), globally suggesting occurrence of a mitochondrial damage-induced senescence. COPD fibroblasts were more susceptible to this sPLA2 XIIA effect than cells from controls subjects. sPLA2 XIIA levels were significantly higher in serum from COPD patients as compared to controls. CONCLUSION: sPLA2 XIIA is involved in senescence in COPD and could be a potential target to dampen this process.

Monitoring Systems in Home Ventilation.

Non-invasive ventilation (NIV) is commonly used at home for patient with nocturnal hypoventilation caused by a chronic respiratory failure. Monitoring NIV is required to optimize the ventilator settings when the lung condition changes over time, and to detect common problems such as unintentional leaks, upper airway obstructions, and patient-ventilator asynchronies. This review describes the accuracy and limitations of the data recorded by the ventilator. To efficiently interpret this huge amount of data, clinician assess the daily use and regularity of NIV utilization, the unintentional leaks and their repartition along the NIV session, the apnea-hypopnea index and the flow waveform, and the patient-ventilator synchrony. Nocturnal recordings of gas exchanges are also required to detect nocturnal alveolar hypoventilation. This review describes the indication, validity criteria, and interpretation of nocturnal oximetry and transcutaneous capnography. Polygraphy and polysomnography are indicated in specific cases to characterize upper airway obstruction. Telemonitoring of the ventilator is a useful tool that should be integrated in the monitoring strategy. The technical solution, information, and limitations are discussed. In conclusion, a basic monitoring package is recommended for all patients complemented by advanced monitoring for specific cases.

Quality versus emergency: How good were ventilation fittings produced by additive manufacturing to address shortages during the COVID19 pandemic?

OBJECTIVE: The coronavirus disease pandemic (COVID-19) increased the risk of shortage in intensive care devices, including fittings with intentional leaks. 3D-printing has been used worldwide to produce missing devices. Here we provide key elements towards better quality control of 3D-printed ventilation fittings in a context of sanitary crisis. MATERIAL AND METHODS: Five 3D-printed designs were assessed for non-intentional (junctional and parietal) and intentional leaks: 4 fittings 3D-printed in-house using FDeposition Modelling (FDM), 1 FDM 3D-printed fitting provided by an independent maker, and 2 fittings 3D-printed in-house using Polyjet technology. Five industrial models were included as controls. Two values of wall thickness and the use of coating were tested for in-house FDM-printed devices. RESULTS: Industrial and Polyjet-printed fittings had no parietal and junctional leaks, and satisfactory intentional leaks. In-house FDM-printed fittings had constant parietal leaks without coating, but this post-treatment method was efficient in controlling parietal sealing, even in devices with thinner walls (0.7 mm vs 2.3 mm). Nevertheless, the use of coating systematically induced absent or insufficient intentional leaks. Junctional leaks were constant with FDM-printed fittings but could be controlled using rubber junctions rather than usual rigid junctions. The properties of Polyjet-printed and FDM-printed fittings were stable over a period of 18 months. CONCLUSIONS: 3D-printing is a valid technology to produce ventilation devices but requires care in the choice of printing methods, raw materials, and post-treatment procedures. Even in a context of sanitary crisis, devices produced outside hospitals should be used only after professional quality control, with precise data available on printing protocols. The mechanical properties of ventilation devices are crucial for efficient ventilation, avoiding rebreathing of CO2, and preventing the dispersion of viral particles that can contaminate health professionals. Specific norms are still required to formalise quality control procedures for ventilation fittings, with the rise of 3D-printing initiatives and the perspective of new pandemics.