Inspiratory muscle training for intensive care patients: A multidisciplinary practical guide for clinicians

ObjectivesTo describe a multidisciplinary approach to inspiratory muscle training (IMT) for patients in the intensive care unit (ICU).BackgroundInspiratory muscle weakness is a known consequence of prolonged mechanical ventilation, and there is emerging evidence that specific IMT can ameliorate this weakness. However, IMT is not yet standard practice in many ICUs, possibly because of the wide variety of methods reported and a lack of published practical guidelines. While the optimal parameters for IMT are yet to be established, we share our detailed methodology which has been shown to be safe in selected ventilator-dependent patients and is the only approach which has been shown to increase quality of life in ICU patients.MethodsPatients who have experienced invasive mechanical ventilation for at least 7 days can commence IMT in either the ventilator-dependent phase or when weaned from mechanical ventilation. Intensity should be prescribed based on maximum inspiratory pressure, which is measurable through the tracheostomy or endotracheal tube via the ventilator or a respiratory pressure meter. Using a removable threshold device, we recommend high-intensity training (5 sets of 6 breaths at a minimum of 50% of maximum inspiratory pressure) performed once per day, supervised by the physiotherapist, with intensity increased daily such that patients can only just complete the 6th breath in each set.ResultsUsing this high-intensity approach, IMT is likely to improve not only inspiratory muscle strength but also quality of life in patients recently weaned from mechanical ventilation of 7 days' duration or longer. Effective IMT requires a multidisciplinary approach to maximise feasibility, with doctors, nurses, and therapists working closely to optimise conditions for successful IMT.ConclusionsThis multidisciplinary approach to implement IMT in ICU patients should assist clinicians in translating best-available evidence into practice, with the potential to enhance patient recovery.     

Notch promotes recurrence of dormant tumor cells following HER2/neu-targeted therapy

Breast cancer mortality is principally due to recurrent tumors that arise from a reservoir of residual tumor cells that survive therapy. Remarkably, breast cancers can recur after extended periods of clinical remission, implying that at least some residual tumor cells pass through a dormant phase prior to relapse. Nevertheless, the mechanisms that contribute to breast cancer recurrence are poorly understood. Using a mouse model of recurrent mammary tumorigenesis in combination with bioinformatics analyses of breast cancer patients, we have identified a role for Notch signaling in mammary tumor dormancy and recurrence. Specifically, we found that Notch signaling is acutely upregulated in tumor cells following HER2/neu pathway inhibition, that Notch signaling remains activated in a subset of dormant residual tumor cells that persist following HER2/neu downregulation, that activation of Notch signaling accelerates tumor recurrence, and that inhibition of Notch signaling by either genetic or pharmacological approaches impairs recurrence in mice. Consistent with these findings, meta-analysis of microarray data from over 4,000 breast cancer patients revealed that elevated Notch pathway activity is independently associated with an increased rate of recurrence. Together, these results implicate Notch signaling in tumor recurrence from dormant residual tumor cells and provide evidence that dormancy is a targetable stage of breast cancer progression.     

Ferulic Acid Modulates Dysfunctional Metabolic Pathways and Purinergic Activities,While Stalling Redox Imbalance and Cholinergic Activities in Oxidative Brain Injury

Neurotoxicity Research - The neuroprotective activities of phenolics have been demonstrated in several studies, with their antioxidant properties playing an influential role. In this study, the...