Project description:Reverse triggering is an underdiagnosed form of patient-ventilator asynchrony in which a passive ventilator-delivered breath triggers a neural response resulting in involuntary patient effort and diaphragmatic contraction. Reverse triggering may significantly impact patient outcomes, and the unique physiology underscores critical potential implications for drug-device-patient interactions. The purpose of this review is to summarize what is known of reverse triggering and its pharmacotherapeutic consequences, with a particular focus on describing reported cases, physiology, historical context, epidemiology, and management. The PubMed database was searched for publications that reported patients presenting with reverse triggering. The current body of evidence suggests that deep sedation may predispose patients to episodes of reverse triggering; as such, providers may consider decreasing sedation or modifying ventilator settings in patients exhibiting ventilator asynchrony as an initial measure. Increased clinician awareness and research focus are necessary to understand appropriate management of reverse triggering and its association with patient outcomes.
Project description:Based on recent single-cell experiments showing that longitudinal myocyte stretch produces both parallel and serial addition of sarcomeres, we developed an anisotropic growth constitutive model with elastic myofiber stretch as the growth stimuli to simulate long-term changes in biventricular geometry associated with alterations in cardiac electromechanics. The constitutive model is developed based on the volumetric growth framework. In the model, local growth evolutions of the myocyte's longitudinal and transverse directions are driven by the deviations of maximum elastic myofiber stretch over a cardiac cycle from its corresponding local homeostatic set point, but with different sensitivities. Local homeostatic set point is determined from a simulation with normal activation pattern. The growth constitutive model is coupled to an electromechanics model and calibrated based on both global and local ventricular geometrical changes associated with chronic left ventricular free wall pacing found in previous animal experiments. We show that the coupled electromechanics-growth model can quantitatively reproduce the following: (1) Thinning and thickening of the ventricular wall respectively at early and late activated regions and (2) Global left ventricular dilation as measured in experiments. These findings reinforce the role of elastic myofiber stretch as a growth stimulant at both cellular level and tissue-level.
Project description:Mechanical ventilation is used to sustain respiratory function in patients with acute respiratory failure. To aid clinicians in consistently selecting lung- and diaphragm-protective ventilation settings, a physiology-based decision support system is needed. To form the foundation of such a system, a comprehensive physiological model which captures the dynamics of ventilation has been developed. The Lung and Diaphragm Protective Ventilation (LDPV) model centers around respiratory drive and incorporates respiratory system mechanics, ventilator mechanics, and blood acid-base balance. The model uses patient-specific parameters as inputs and outputs predictions of a patient's transpulmonary and esophageal driving pressures (outputs most clinically relevant to lung and diaphragm safety), as well as their blood pH, under various ventilator and sedation conditions. Model simulations and global optimization techniques were used to evaluate and characterize the model. The LDPV model is demonstrated to describe a CO2 respiratory response that is comparable to what is found in literature. Sensitivity analysis of the model indicate that the ventilator and sedation settings incorporated in the model have a significant impact on the target output parameters. Finally, the model is seen to be able to provide robust predictions of esophageal pressure, transpulmonary pressure and blood pH for patient parameters with realistic variability. The LDPV model is a robust physiological model which produces outputs which directly target and reflect the risk of ventilator-induced lung and diaphragm injury. Ventilation and sedation parameters are seen to modulate the model outputs in accordance with what is currently known in literature.
Project description:Mechanical ventilation can cause acute diaphragm atrophy and injury, and this is associated with poor clinical outcomes. Although the importance and impact of lung-protective ventilation is widely appreciated and well established, the concept of diaphragm-protective ventilation has recently emerged as a potential complementary therapeutic strategy. This Perspective, developed from discussions at a meeting of international experts convened by PLUG (the Pleural Pressure Working Group) of the European Society of Intensive Care Medicine, outlines a conceptual framework for an integrated lung- and diaphragm-protective approach to mechanical ventilation on the basis of growing evidence about mechanisms of injury. We propose targets for diaphragm protection based on respiratory effort and patient-ventilator synchrony. The potential for conflict between diaphragm protection and lung protection under certain conditions is discussed; we emphasize that when conflicts arise, lung protection must be prioritized over diaphragm protection. Monitoring respiratory effort is essential to concomitantly protect both the diaphragm and the lung during mechanical ventilation. To implement lung- and diaphragm-protective ventilation, new approaches to monitoring, to setting the ventilator, and to titrating sedation will be required. Adjunctive interventions, including extracorporeal life support techniques, phrenic nerve stimulation, and clinical decision-support systems, may also play an important role in selected patients in the future. Evaluating the clinical impact of this new paradigm will be challenging, owing to the complexity of the intervention. The concept of lung- and diaphragm-protective ventilation presents a new opportunity to potentially improve clinical outcomes for critically ill patients.
Project description:Surgical treatment of bronchobiliary fistula (BBF) is difficult. A 47-year-old woman presented with a cough with yellow yielding sputum due to BBF. The patient had the adhesion of the liver, diaphragm, and lung. We performed liver, diaphragm, and lung resections. Patient had a large defect of diaphragm. Diaphragm reconstruction was performed using a pedicled reverse latissimus dorsi muscle flap. No flap necrosis was observed. Seven months after surgery, the patient did not present yellow yielding sputum and the BBF was not observed in the computed tomography. This surgical procedure was useful for treating the diaphragm defect both safely and easily. We believe that the reverse pedicled latissimus dorsi muscle flap is a reliable alternative for large diaphragm reconstruction after severe BBF.
Project description:TIGIT (T cell immunoreceptor with Ig and ITIM domains) is a co-inhibitory receptor expressed on various immune cells, including T cells, NK cells, and dendritic cells. TIGIT interacts with different ligands, such as CD155 and CD112, which are highly expressed on cancer cells, leading to the suppression of immune responses. Recent studies have highlighted the importance of TIGIT in regulating immune cell function in the tumor microenvironment and its role as a potential therapeutic target, especially in the field of lung cancer. However, the role of TIGIT in cancer development and progression remains controversial, particularly regarding the relevance of its expression both in the tumor microenvironment and on tumor cells, with prognostic and predictive implications that remain to date essentially undisclosed. Here, we provide a review of the recent advances in TIGIT-blockade in lung cancer, and also insights on TIGIT relevance as an immunohistochemical biomarker and its possible theranostic implications.
Project description:BACKGROUND:QRS duration is commonly used to select heart failure patients for cardiac resynchronization therapy (CRT). However, not all patients respond to CRT, and recent data suggest that direct assessments of mechanical dyssynchrony may better predict chronic response. Echo-Doppler methods are being used increasingly, but these principally rely on longitudinal motion (epsilonll). It is unknown whether this analysis yields qualitative and/or quantitative results similar to those based on motion in the predominant muscle-fiber orientation (circumferential; epsiloncc). METHODS AND RESULTS:Both epsilonll and epsiloncc strains were calculated throughout the left ventricle from 3D MR-tagged images for the full cardiac cycle in dogs with cardiac failure and a left bundle conduction delay. Dyssynchrony was assessed from both temporal and regional strain variance analysis. CRT implemented by either biventricular (BiV) or left ventricular-only (LV) pacing enhanced systolic function similarly and correlated with improved dyssynchrony based on epsiloncc-based metrics. In contrast, longitudinal-based analyses revealed significant resynchronization with BiV but not LV for the overall cycle and correlated poorly with global functional benefit. Furthermore, unlike circumferential analysis, epsilonll-based indexes indicated resynchronization in diastole but much less in systole and had a lower dynamic range and higher intrasubject variance. CONCLUSIONS:Dyssynchrony assessed by longitudinal motion is less sensitive to dyssynchrony, follows different time courses than those from circumferential motion, and may manifest CRT benefit during specific cardiac phases depending on pacing mode. These results highlight potential limitations to epsilonll-based analyses and support further efforts to develop noninvasive synchrony measures based on circumferential deformation.
Project description:ObjectivesLung- and diaphragm-protective ventilation is a novel concept that aims to limit the detrimental effects of mechanical ventilation on the diaphragm while remaining within limits of lung-protective ventilation. The premise is that low breathing effort under mechanical ventilation causes diaphragm atrophy, whereas excessive breathing effort induces diaphragm and lung injury. In a proof-of-concept study, we aimed to assess whether titration of inspiratory support based on diaphragm effort increases the time that patients have effort in a predefined "diaphragm-protective" range, without compromising lung-protective ventilation.DesignRandomized clinical trial.SettingMixed medical-surgical ICU in a tertiary academic hospital in the Netherlands.PatientsPatients (n = 40) with respiratory failure ventilated in a partially-supported mode.InterventionsIn the intervention group, inspiratory support was titrated hourly to obtain transdiaphragmatic pressure swings in the predefined "diaphragm-protective" range (3-12 cm H2O). The control group received standard-of-care.Measurements and main resultsTransdiaphragmatic pressure, transpulmonary pressure, and tidal volume were monitored continuously for 24 hours in both groups. In the intervention group, more breaths were within "diaphragm-protective" range compared with the control group (median 81%; interquartile range [64-86%] vs 35% [16-60%], respectively; p < 0.001). Dynamic transpulmonary pressures (20.5 ± 7.1 vs 18.5 ± 7.0 cm H2O; p = 0.321) and tidal volumes (7.56 ± 1.47 vs 7.54 ± 1.22 mL/kg; p = 0.961) were not different in the intervention and control group, respectively.ConclusionsTitration of inspiratory support based on patient breathing effort greatly increased the time that patients had diaphragm effort in the predefined "diaphragm-protective" range without compromising tidal volumes and transpulmonary pressures. This study provides a strong rationale for further studies powered on patient-centered outcomes.