Jesus Gonzalez-Bermejo

Background Diaphragm pacing offers an alternative to mechanical ventilation for diaphragm paralysis, yet commercial devices use fixed parameters and lack real-time physiological feedback. We developed and bench-validated an embedded diaphragmatic stimulator that classifies respiratory status and trend from real-time measurements of end-tidal CO2 (PetCO2) and oxygen saturation (SpO2). Methods We engineered a fuzzy-logic–based embedded controller to identify patient condition and trend from real-time PetCO2 and SpO2. The bench setup used an ASL5000 breathing simulator and CapnoStream as the PetCO2 reference; SpO2 was varied with a Vpad-A1 simulator. Multiple clinical scenarios and state transitions were reproduced to reflect real-world contexts. We quantified PetCO2 agreement (Bland–Altman, intraclass correlation coefficient [ICC]) and assessed classification agreement for status (normal/abnormal/critical) and trend (improving/stable/deteriorating) using weighted Cohen’s Kappa. Results Across 379 measurements covering standard and hypocapnic patient profiles, PetCO2 exhibited a mean bias of 0.22 mmHg relative to the reference capnometer, with Bland–Altman limits of agreement −1.7 to 1.25 mmHg and ICC = 0.99. Classification of respiratory status (normal/abnormal/critical) showed perfect agreement with the computational reference (weighted Cohen’s κ = 1.0), and trend classification demonstrated excellent agreement (κ > 0.92). Conclusion The embedded electrical stimulator developed successfully integrates PetCO2 and SpO2 monitoring to identify patient status and trends with high agreement, across physiological situations reproduced in a bench model. This represents a key step toward a closed-loop system capable of modulating breathing patterns based on physiological respiratory inputs.

Examples of cardiac and skeletal muscle pathology findings on autopsies of 2 patients

Treatment modalities and reported adverse events by quartile of period of inclusion.

Methods concerning Immune-checkpoint proteins profiling on peripheral blood mononuclear cells and Circulating immune checkpoint agents drug monitoring

Proposed management algorithm for ICI-myotoxicities as a function of severity criteria grading

Delay between presentation for ICI myocarditis, appearance of life-threatening myotoxicity criteria (severity grade 4, Supplementary Table 5 for details concerning grading) and start of the immunosuppressive treatments (with dose) in severe ICI-myocarditis patients requiring abatacept.

Example of the first severe ICI-myocarditis case treated with abatacept guided by real-time immune-monitoring assessment of CD86RO (CD86 receptor occupancy) on circulating monocytes.

Diagnostic certainty criteria for ICI-myocarditis

Diagnostic work-up for suspected ICI-myocarditis and evaluation of severity criteria

Definitions used for adjudication and grading of the different evaluated events