Background: Post-intensive care syndrome (PICS) affects the quality of life (QOL) of survivors of critical illness. Although PICS persists for a long time, the longitudinal changes in each component and their interrelationships over time both remain unclear. This multicenter prospective study investigated the 2-year trajectory of PICS and its components as well as factors contributing to deterioration or recovery in mechanically ventilated patients with coronavirus disease 2019 (COVID-19), and also attempted to identify possible countermeasures. Methods: Patients who survived COVID-19 requiring mechanical ventilation completed questionnaires on the Barthel index, Short-Memory Questionnaire, Hospital Anxiety and Depression Scale, and EuroQol 5 dimensions 5-level every six months over a two-year period. Scores were weighted to account for dropouts, and the trajectory of each functional impairment was evaluated with alluvial diagrams. The prevalence of PICS and factors impairing or restoring function were examined using generalized estimating equations considering trajectories. Results: Among 334 patients, PICS prevalence rates in the four completed questionnaires were 72.1, 78.5, 77.6, and 82.0%, with cognitive impairment being the most common and lower QOL being noted when multiple impairments coexisted. Physical function and QOL indicated that many patients exhibited consistent trends of either recovery or deterioration. In contrast, cognitive function and mental health revealed considerable variability, with many patients showing fluctuating ratings in the later surveys. Delirium was associated with worse physical and mental health and poor QOL, while prolonged ventilation was associated with poor QOL. Living with family was associated with the recovery of all functions and QOL, while extracorporeal membrane oxygenation (ECMO) was associated with the recovery of cognitive function and mental health. Conclusions: Critically ill patients had PICS for a long period and followed different trajectories for each impairment component. Based on trajectories, known PICS risk factors such as prolonged ventilation and delirium were associated with impaired recovery, while ECMO and the presence of family were associated with recovery from PICS. In critically ill COVID-19 patients, delirium management and family interventions may play an important role in promoting recovery from PICS. Trial registration number: UMIN000041276, August 01, 2020.

Doxorubicin (DOX) induces dose-dependent cardiotoxicity via oxidative stress and abnormal mitochondrial function in the myocardium. Therefore, a noninvasive in vivo imaging procedure for monitoring the redox status of the heart may aid in monitoring diseases and developing treatments. However, an appropriate technique has yet to be developed. In this study, we demonstrate a technique for detecting and visualizing the redox status of the heart using in vivo dynamic nuclear polarization–magnetic resonance imaging (DNP–MRI) with 3-carbamoyl-PROXYL (CmP) as a molecular imaging probe. Male C57BL/6N mice were administered DOX (20 mg/kg) or saline. DNP–MRI clearly showed a slower DNP signal reduction in the DOX group than in the control group. Importantly, the difference in the DNP signal reduction rate between the two groups occurred earlier than that detected by physiological examination or clinical symptoms. In an in vitro experiment, KCN (an inhibitor of complex IV in the mitochondrial electron transport chain) and DOX inhibited the electron paramagnetic resonance change in H9c2 cardiomyocytes, suggesting that the redox metabolism of CmP in the myocardium is mitochondrion-dependent. Therefore, this molecular imaging technique has the potential to monitor the dynamics of redox metabolic changes in DOX-induced cardiomyopathy and facilitate an early diagnosis of this condition.

Acute exacerbation of interstitial pneumonia (AE-IP) is associated with high mortality rates. Although the risk factors for AE-IP have been extensively studied, given the small sample sizes, only a few risk factors have been established. This study aimed to investigate the postoperative mortality and factors associated with AE-IP. This retrospective study included 482 patients with a preoperative diagnosis of IP who underwent noncardiac surgery between December 2012 and April 2020. AE-IP was diagnosed by a radiologist using computed tomography when worsening respiratory symptoms were observed within 1 month postoperatively. The Cox proportional hazards model was used to compare mortality rates. Candidate factors associated with AE-IP were identified through logistic regression analysis using the variable selection method, followed by case-control analysis using propensity score matching to determine possible factors associated with AE-IP. The multivariable-adjusted hazard ratios for all-cause and IP-related deaths were significantly higher in patients with AE-IP than in those without AE-IP. Multivariable analysis with variable selection suggested that male sex, higher C-reactive protein (CRP) levels, fraction of inspired oxygen (FiO2) ≥ 60%, and non-lung surgery were candidate factors associated with AE-IP. Case-control analysis using propensity score matching demonstrated that patients with AE-IP had higher CRP levels (P = 0.044) and frequency of FiO2 ≥ 60% (P = 0.035) than those without AE-IP. Furthermore, a positive, nearly linear relationship was observed between FiO2 ≥ 60% duration and AE-IP incidence. Intraoperative management with FiO2 ≥ 60% and high preoperative CRP levels were significantly associated with postoperative AE-IP.

Objective: To implement early rehabilitation interventions by physical therapists is recommended. However, the effectiveness of early rehabilitation for severe coronavirus disease 2019 (COVID-19) patients in the prevention of post-intensive care syndrome (PICS) is unclear. We analyzed a multicenter prospective observational study (Post-Intensive Care outcomeS in patients with COronaVIrus Disease 2019) to examine the association between early rehabilitation interventions and PICS physical impairment.Methods: An analysis was performed on COVID-19 patients who were admitted to intensive care units (ICUs) between March 2020 and March 2021, and required mechanical ventilation. The primary outcome was the incidence of PICS physical impairment (Barthel Index≤90) after one year. Multivariate logistic regression analysis was used to estimate the association between early rehabilitation interventions and PICS physical impairment by adjusting ICU mobility scale (IMS) during seven-day following ICU admission, and clinically relevant risk factors.Results: The analysis included 259 patients, 54 of whom developed PICS physical impairment one year later. In 81 patients, physical therapists intervened within seven days of ICU admission. There was no significant difference in mean IMS by day seven of admission between the early and non-early rehabilitation patients (0.70 and 0.61, respectively). Multivariate logistic regression analysis showed that early rehabilitation interventions were significantly associated with a low incidence of PICS physical impairment (odds ratio, 0.294; 95% confidence interval, 0.123–0.706; p=0.006).Conclusion: Early rehabilitation interventions by physical therapists were an independent factor associated with the decreased development of PICS physical impairment at one year, even though early rehabilitation had no significant effect on IMS.