American journal of respiratory and critical care medicine
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Am. J. Respir. Crit. Care Med. · Apr 2023
NRF2 Activation Reprogrammes Defects in Oxidative Metabolism to Restore Macrophage Function in COPD.
Rationale: Chronic obstructive pulmonary disease (COPD) is a disease characterized by persistent airway inflammation and disordered macrophage function. The extent to which alterations in macrophage bioenergetics contribute to impaired antioxidant responses and disease pathogenesis has yet to be fully delineated. Objectives: Through the study of COPD alveolar macrophages (AMs) and peripheral monocyte-derived macrophages (MDMs), we sought to establish if intrinsic defects in core metabolic processes drive macrophage dysfunction and redox imbalance. ⋯ Consequently, selective activation of NRF2 resets the COPD transcriptome, resulting in increased generation of TCA cycle intermediaries, improved energetic status, favorable redox balance, and recovery of macrophage function. Conclusions: In COPD, an inherent loss of metabolic plasticity leads to metabolic exhaustion and reduced redox capacity, which can be rescued by activation of the NRF2 pathway. Targeting these defects, via NRF2 augmentation, may therefore present an attractive therapeutic strategy for the treatment of the aberrant airway inflammation described in COPD.
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Am. J. Respir. Crit. Care Med. · Apr 2023
Meta AnalysisMinimal Clinically Important Difference in the Six-Minute Walk Distance for Patients with Pulmonary Arterial Hypertension.
Rationale: The 6-minute-walk distance (6MWD) is an important clinical and research metric in pulmonary arterial hypertension (PAH); however, there is no consensus about what minimal change in 6MWD is clinically significant. Objectives: We aimed to determine the minimal clinically important difference in the 6MWD. Methods: We performed a meta-analysis using individual participant data from eight randomized clinical trials of therapy for PAH submitted to the U. ⋯ The minimal clinically important difference did not differ by age, sex, race, pulmonary hypertension etiology, body mass index, use of background therapy, or World Health Organization functional class. Conclusions: We estimated a 6MWD minimal clinically important difference of approximately 33 meters for adults with PAH. Our findings can be applied to the design of clinical trials of therapies for PAH.
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Am. J. Respir. Crit. Care Med. · Apr 2023
Multicenter Study Observational StudyNurse-to-Nurse Familiarity and Mortality in the Critically Ill. A Multicenter Observational Study.
Rationale: Nurse-to-nurse familiarity at work should strengthen the components of teamwork and enhance its efficiency. However, its impact on patient outcomes in critical care remains poorly investigated. Objectives: To explore the role of nurse-to-nurse familiarity on inpatient deaths during ICU stay. ⋯ The adjusted model showed a lower risk of a shift with mortality when nurse-to-nurse familiarity increased in the shift (relative risk, 0.90; 95% confidence interval per 10 shifts, 0.82-0.98; P = 0.012). Low nurse-to-nurse familiarity during the shift combined with suboptimal patient-to-nurse and patient-to-assistant nurse ratios (suboptimal if >2.5 and >4, respectively) were associated with increased risk of shift with mortality (relative risk, 1.84; 95% confidence interval, 1.15-2.96; P < 0.001). Conclusions: Shifts with low nurse-to-nurse familiarity were associated with an increased risk of patient deaths.