Background: This systematic review and meta-analysis of randomized clinical trials aimed to investigate the efficacy of early mobilization among critically ill adult patients. Methods: We searched CENTRAL, MEDLINE, and Igaku-Chuo-Zasshi (a Japanese bibliographic database) databases until April 2019 and included randomized control trials to compare early mobilization started within 1 week of intensive care unit (ICU) admission and earlier-than-usual care with the usual care or mobilization initiated later than the intervention. Two authors independently extracted the data of the included studies and assessed their quality. The primary outcomes were in-hospital mortality, length of ICU/hospital stay, and health-related quality of life (QOL). Results: Among 1085 titles/abstracts screened, 11 studies (including 1322 patients) were included in the meta-analysis, which was conducted using the random-effects model. The pooled relative risk for in-hospital mortality comparing early mobilization to usual care (control) was 1.12 (95% CI [confidence interval]: 0.80 to 1.58, I² = 0%). The pooled mean differences for duration of ICU and hospital stay were -1.54 (95% CI: -3.33 to 0.25, I² = 90%) and -2.86 (95% CI: -5.51 to -0.21, I² = 85%), respectively. The pooled mean differences at 6 months post-discharge, as measured by the Short Form 36-Item Health Survey and Euro-QOL EQ-5D, were 4.65 (95% CI: -16.13 to 25.43, I² = 86%) for physical functioning and 0.29 (95% CI: -11.19 to 11.78, I² = 66%) for the visual analog scale. Conclusions: Our study indicated no apparent differences between early mobilization and usual care in terms of in-hospital mortality and health-related QOL. Detailed larger studies are warranted to evaluate the impact of early mobilization on in-hospital mortality and health-related QOL in critically ill patients. Trial registration: PROSPERO (identifier CRD42019139265)

Background: Although the combination of rehabilitation and nutrition may be important for the prevention of intensive care unit (ICU)-acquired weakness, a protocolized intervention of this combination has not yet been reported. We herein developed an original combined protocol and evaluated its efficacy. Methods: In this single-center historical control study, we enrolled adult patients admitted to the ICU. Patients in the control group received standard care, while those in the intervention group received the protocol-based intervention. The ICU mobility scale was used to set goals for early mobilization and a neuromuscular electrical stimulation was employed when patients were unable to stand. The nutritional status was assessed for nutritional therapy, and target calorie delivery was set at 20 or 30 kcal/kg/day and target protein delivery at 1.8 g/kg/day in the intervention group. The primary endpoint was a decrease in femoral muscle volume in 10 days assessed by computed tomography. Results: Forty-five patients in the control group and 56 in the intervention group were included in the analysis. Femoral muscle volume loss was significantly lower in the intervention group (11.6 vs 14.5%, p = 0.03). The absolute risk difference was 2.9% (95% CI 0.1–5.6%). Early mobilization to a sitting position by day 10 was achieved earlier (p = 0.03), and mean calorie delivery (20.1 vs. 16.8 kcal/kg/day, p = 0.01) and mean protein delivery (1.4 vs. 0.8 g/kg/day, p < 0.01) were higher in the intervention group. Conclusion: The protocolized intervention, combining early mobilization and high-protein nutrition, contributed to the achievement of treatment goals and prevention of femoral muscle volume loss. Trial registration number: The present study is registered at the University Hospital Medical Information Network-clinical trials registry (UMIN000040290, Registration date: May 7, 2020).

Pediatric patients, especially in the preverbal stage, cannot self-report intensity of pain therefore several validated observational tools, including the Face, Legs, Activity, Cry, Consolability (FLACC) Behavioral Scale, have been used as a benchmark to evaluate pediatric pain. Unfortunately, this scale is currently unavailable in Japanese, precluding its widespread use in Japanese hospitals. To translate and verify the validity and reliability of the Japanese version of the FLACC Behavioral Scale. Back-translation was first conducted by eight medical researchers, then an available sample of patients at the University of Tsukuba Pediatric Intensive Care Unit (from May 2017 to August 2017) was enrolled in a clinical study. Two researchers evaluated the validity of the translated FLACC Behavioral Scale by weighted kappa coefficient and intraclass correlation coefficients (ICC). Observational pain was simultaneously measured by the visual analog scale (VAS obs) and reliability was evaluated by correlation analysis. The original author approved the translation. For the clinical study, a total of 121 observations were obtained from 24 pediatric patients. Agreement between observers was highly correlated for each of the FLACC categories (Face: κ = 0.85, Leg: κ = 0.74, Activity: κ = 0.89, Cry: κ = 0.93, Consolability: κ = 0.93) as well as the total score (Total: κ = 0.95,). Correlation analysis demonstrated a good criterion validation between the FLACC scale and the VAS obs. (r = 0.96) Our Japanese version of the FLACC Behavioral Scale shows high validity and reliability.

Since December 2019, the SARS-CoV-2 (COVID-19) pandemic has transfixed the medical world. COVID-19 symptoms vary from mild to severe and underlying chronic conditions such as pulmonary/cardiovascular disease and diabetes induce excessive inflammatory responses to COVID-19 and these underlying chronic diseases are mediated by endothelial dysfunction. Acute respiratory distress syndrome (ARDS) is the most common cause of death in COVID-19 patients, but coagulation induced by excessive inflammation, thrombosis, and disseminated intravascular coagulation (DIC) also induce death by multiple-organ dysfunction syndrome. These associations imply that maintaining endothelial integrity is crucial for favorable prognoses with COVID-19 and therapeutic intervention to support this may be beneficial. Here, we summarize the extent of heart injuries, ischemic stroke and hemorrhage, acute kidney injury, and liver injury caused by immune-mediated endothelial dysfunction that result in the phenomenon of multi-organ dysfunction seen in COVID-19 patients. Moreover, the potential therapeutic effect of angiotensin receptor blockers and angiotensin-converting enzyme inhibitors that improve endothelial dysfunction as well as the bradykinin storm are discussed.

Among the dysfunctions and pathologies associated with sepsis, the underlying molecular mechanisms of sepsis-induced acute lung injury (ALI) are poorly understood. Endothelin (ET)-1, a potent vasoconstrictor and pro-inflammatory peptide, is known to be involved in the pathogenesis of ALI in a rat model of sepsis. Here, we investigated whether landiolol hydrochloride, an ultra-short-acting β-blocker, plays a crucial role in ameliorating and attenuating LPS-induced ALI through modulation of the ET-1 system. Male Wistar rats at 8weeks of age were administered with either saline or lipopolysaccharide (LPS) for three hours (3h) and some of the LPS-administered rats were continuously treated with landiolol for 3h. ALI was induced by LPS, including levels of both circulatory and pulmonary TNF-α and IL-6 but [PaO2] was significantly decreased. LPS also induced a significant increase in levels of pulmonary ET-1 and ET-A receptor, but levels of ET-B receptor, which has vasodilating effects, were remarkably diminished. Further, LPS administration upregulated the pulmonary expression of HIF-1α. Finally, the treatment of LPS-administered rats with landiolol for 3h ameliorated and prevented ALI, normalized the altered levels of pulmonary ET-1 and ET-A receptors. Landiolol also induced significant down-regulation of ET-B receptor in lung tissues in the early hours (phase) of sepsis. However, Landiolol treatment had no effect on the up-regulated inflammatory mediators (TNF-α, IL-6) in both plasma and lung tissues during sepsis, and expression of pulmonary HIF-1α also remained unchanged after landiolol treatment. Collectively, these data led us to conclude that landiolol may ameliorate sepsis-induced ALI via the pulmonary ET system.

Aim To determine the relationship between the delirium of patients with mechanical ventilation during intensive care unit (ICU) stay and delusional memory after ICU discharge. Design Prospective cohort study. Methods Delirium in adult patients who received mechanical ventilation for more than 24 hr was assessed twice daily using the Confusion Assessment Method for the ICU. Delusional memories were evaluated using the ICU Memory Tool 5–10 days after ICU discharge. The associations between the presence of delirium during the ICU stay and delusional memories were evaluated. Results Of 60 enrolled patients, 62% had delirium during their ICU stay, and 68% experienced delusional memories 5–10 days after discharge. Delirium during ICU stay was an independent factor to experience delusional memories following discharge. Preventing delirium during ICU stay might reduce delusional memory. We recommend that patients with delirium during their ICU stay should be carefully followed up after discharge from the ICU.