Sex Disparities in Applied Force on Maxillary Incisors Among Novices During Laryngoscopy Using a High-Fidelity Simulator: A Prospective Observational Study.

Endotracheal intubation (ETI) is a common and crucial intervention. Whether the performance of ETI differs according to the sex of the laryngoscopist remains unclear. The aim of this study was to assess sex disparities in markers of ETI performance among novices using a high-fidelity simulator. This prospective observational study was conducted from April 2017 to March 2019 in a public medical university. In total, 209 medical students (4th and 5th grade) without clinical ETI experience were recruited. Of the 209 students, 64 (30.6%) were female. The participants used either a Macintosh direct laryngoscope or C-MAC video laryngoscope in combination with a stylet or gum-elastic bougie to perform ETI on a high-fidelity simulator. The primary endpoint was the maximum force applied on the maxillary incisors during laryngoscopy. The secondary endpoint was the time to ETI. The implanted sensors in the simulator automatically quantified the force and time to ETI. The maximum force applied on the maxillary incisors was approximately 30% lower in the male than female group for all laryngoscopes and intubation aids examined (all P < 0.001). Similarly, the time to ETI was approximately 10% faster in the male than female group regardless of the types of laryngoscopes and intubation aids used (all P < 0.05). In this study, male sex was associated with a lower maximum force applied on the maxillary incisors during both direct and indirect laryngoscopy performed by novices. A clinical study focusing on sex differences in ETI performance is needed to validate our findings.

Postintensive care syndrome family: A comprehensive review.

Families of critically ill patients are predisposed to tremendous burdens when their relatives are admitted to the intensive care unit (ICU). Postintensive care syndrome family (PICS-F) can be described as a devastated life, encompassing psychological, physical, and socioeconomical burdens that begin with the emotional impact experienced by the family when the patient is admitted to the ICU. PICS-F was primarily proposed as a clinically significant psychological impairment, but it needs to be extended beyond the psychological impairment of the family to include physical and socioeconomical impairments in the future. The prevalence of physiological problems including depression, anxiety and post-traumatic syndrome is 20-40%, and that of non-physiological problems including fatigue is 15% at 6 months after the ICU stay. Assessment of PICS-F was frequently conducted at 3- or 6-month points, although the beginning of the evaluation was based on different assessment points among each of the studies. Families of ICU patients need to be given and understand accurate information, such as the patient's diagnosis, planned care, and prognosis. Prevention of PICS-F requires a continuous bundle of multifaceted and/or multidisciplinary interventions including providing a family information leaflet, ICU diary, communication facilitators, supportive grief care, and follow-up, for the patient and families from during the ICU stay to after discharge from the ICU. This is the first comprehensive review of PICS-F to address the concept, risk factors, assessment tools, prevalence, and management to prevent PICS-F to facilitate acute care physicians' understanding of PICS-F.

Post-intensive care syndrome: Recent advances and future directions.

Post-intensive care syndrome comprises physical, cognitive, and mental impairments in patients treated in an intensive care unit (ICU). It occurs either during the ICU stay or following ICU discharge and is related to the patients' long-term prognosis. The same concept also applies to pediatric patients, and it can greatly affect the mental status of family members. In the 10 years since post-intensive care syndrome was first proposed, research has greatly expanded. Here, we summarize the recent evidence on post-intensive care syndrome regarding its pathophysiology, epidemiology, assessment, risk factors, prevention, and treatments. We highlight new topics, future directions, and strategies to overcome post-intensive care syndrome among people treated in an ICU. Clinical and basic research are still needed to elucidate the mechanistic insights and to discover therapeutic targets and new interventions for post-intensive care syndrome.

Post-infarction Left Ventricular Free Wall Rupture Diagnosed by Contrast-Enhanced Computed Tomography: A Case Report.

A 70-year-old Japanese woman with hypertension, dyslipidemia, and diabetes mellitus complained of abdominal discomfort and vomiting and was brought to our emergency department by ambulance two days later with impaired consciousness. Her vital signs suggested shock with a heart rate of 120 bpm. Electrocardiogram and initial transthoracic echocardiography suggested an inferior wall ST-elevation myocardial infarction, but the altered consciousness was inconsistent. Contrast-enhanced computed tomography was urgently performed to further clarify the cause. It revealed pericardial effusion and apparent extravasation from the left ventricular wall, confirming the early definitive diagnosis of left ventricular free wall rupture. The patient underwent successful emergent surgical repair without sequelae. Differential diagnosis of left ventricular free wall rupture is important in patients with ST-elevation myocardial infarction and impaired consciousness. Contrast-enhanced computed tomography allows early diagnosis and treatment of this life-threatening complication.

Relationship between critical care nutrition and post-intensive care syndrome in surviving ventilated patients with COVID-19: a multicenter prospective observational study.

The impact of nutrition therapy in the acute phase on post-intensive care syndrome (PICS) remains unclear. We conducted a multicenter prospective study on adult patients with COVID-19 who required mechanical ventilation for more than three days. The questionnaire was mailed after discharge. Physical PICS, defined as less than 90 points on the Barthel index (BI), was assigned as the primary outcome. We examined the types of nutrition therapy in the first week that affected PICS components. 269 eligible patients were evaluated 10 months after discharge. Supplemental parenteral nutrition (SPN) >400 kcal/day correlated with a lower occurrence of physical PICS (10% vs 21.92%, p = 0.042), whereas the amounts of energy and protein provided, early enteral nutrition, and a gradual increase in nutrition delivery did not, and none correlated with cognitive or mental PICS. A multivariable regression analysis revealed that SPN had an independent impact on physical PICS (odds ratio 0.33, 95% CI 0.12-0.92, p = 0.034), even after adjustments for age, sex, body mass index and severity. Protein provision ≥1.2 g/kg/day was associated with a lower occurrence of physical PICS (odds ratio 0.42, 95% CI 0.16-1.08, p = 0.071). In conclusion, SPN in the acute phase had a positive impact on physical PICS for ventilated patients with COVID-19.

Novel Peritoneal Sclerosis Rat Model Developed by Administration of Bleomycin and Lansoprazole.

In our preliminary experiment, peritoneal sclerosis likely induced by peritoneal dialysis was unexpectedly observed in the livers of rats given bleomycin and lansoprazole. We examined whether this peritoneal thickening around the liver was time-dependently induced by administration of both drugs. Male Wistar rats were injected with bleomycin and/or lansoprazole for 2 or 4 weeks. The 3YB-1 cell line derived from rat fibroblasts was treated by bleomycin and/or lansoprazole for 24 h. The administration of both drugs together, but not individually, thickened the peritoneal tissue around the liver. There was accumulation of collagen fibers, macrophages, and eosinophils under mesothelial cells. Expressions of Col1a1, Mcp1 and Mcp3 genes were increased in the peritoneal tissue around the liver and in 3YB-1 cells by the administration of both drugs together, and Opn genes had increased expressions in this tissue and 3YB-1 cells. Mesothelial cells indicated immunoreactivity against both cytokeratin, a mesothelial cell marker, and αSMA, a fibroblast marker, around the livers of rats given both drugs. Administration of both drugs induced the migration of macrophages and eosinophils and induced fibrosis associated with the possible activation of fibroblasts and the possible promotion of the mesothelial-mesenchymal transition. This might become a novel model of peritoneal sclerosis for peritoneal dialysis.

Instruments to assess post-intensive care syndrome assessment: a scoping review and modified Delphi method study.

BACKGROUND: The assessment of post-intensive care syndrome (PICS) is challenging due to the numerous types of instruments. We herein attempted to identify and propose recommendations for instruments to assess PICS in intensive care unit (ICU) survivors. METHODS: We conducted a scoping review to identify PICS follow-up studies at and after hospital discharge between 2014 and 2022. Assessment instruments used more than two times were included in the modified Delphi consensus process. A modified Delphi meeting was conducted three times by the PICS committee of the Japanese Society of Intensive Care Medicine, and each score was rated as not important (score: 1-3), important, but not critical (4-6), and critical (7-9). We included instruments with ≥ 70% of respondents rating critical and ≤ 15% of respondents rating not important. RESULTS: In total, 6972 records were identified in this scoping review, and 754 studies were included in the analysis. After data extraction, 107 PICS assessment instruments were identified. The modified Delphi meeting reached 20 PICS assessment instrument recommendations: (1) in the physical domain: the 6-min walk test, MRC score, and grip strength, (2) in cognition: MoCA, MMSE, and SMQ, (3) in mental health: HADS, IES-R, and PHQ-9, (4) in the activities of daily living: the Barthel Index, IADL, and FIM, (5) in quality of life: SF-36, SF-12, EQ-5D-5L, 3L, and VAS (6), in sleep and pain: PSQI and Brief Pain Inventory, respectively, and (7) in the PICS-family domain: SF-36, HADS, and IES-R. CONCLUSION: Based on a scoping review and the modified Delphi method, 20 PICS assessment instruments are recommended to assess physical, cognitive, mental health, activities of daily living, quality of life, sleep, and pain in ICU survivors and their families.

Gender Disparities in First Authorship at Three Medical Universities in an Area Affected by the Great East Japan Earthquake.

The Great East Japan Earthquake that occurred on March 11, 2011, was one of the largest natural disasters in modern times. Publication in medical journals is important aspects of the academic promotion process, and is thus important for all scientists. However, little is known about whether and how substantial natural disasters affect gender disparities in academic productivity in disaster-affected areas. We hypothesized that the Great East Japan Earthquake widened the existing disparities in scientific publishing between male and female researchers. To test this hypothesis, this retrospective observational study using existing databases was conducted. We extracted from the MEDLINE database all types of biomedical articles published from March 11, 2007, to March 11, 2015, by three medical universities in a disaster-affected area of Japan. Differences in the proportion of female first authorship during the 4 years before and after the Great East Japan Earthquake were compared. A total of 5,873 papers were analyzed. The proportion of female first authors significantly declined after the Great East Japan Earthquake (20.5% vs. 14.1%; odds ratio 0.64; 95% confidence interval 0.56-0.73). A similar trend was identified across all prespecified subgroups, including clinical department; original article; public medical university; and prestigious journal with impact factor >6. Reference data from two medical universities minimally affected by the Great East Japan Earthquake showed the opposite trend. These results collectively suggest that large natural disasters can reinforce existing gender disparities in first authorship in biomedicine.

Ultrasound-based upper limb muscle thickness is useful for screening low muscularity during intensive care unit admission: A retrospective study.

BACKGROUND & AIMS: Malnutrition is associated with poor outcomes. Muscle mass is an important malnutrition indicator included in Global Leadership Initiative on Malnutrition (GLIM) criteria. Although bioelectrical impedance analysis and dual-energy X-ray absorptiometry are common muscle mass assessment methods, they are unreliable during intensive care unit (ICU) admission due to the influence of dynamic fluid changes. We hypothesized that ultrasound-based upper limb muscle assessment would be useful for assessing muscularity at ICU admission. METHODS: We retrospectively analyzed prospectively obtained ultrasound data from patients admitted to an ICU. We excluded patients without computed tomography (CT) imaging of the third lumbar vertebra within 2 days of ICU admission. Primary outcomes were the diagnostic utility of ultrasound-based upper limb muscle thickness for assessing low muscularity by CT. Low muscularity was defined as a skeletal muscle index of 36.0 cm2/m2 for males and 29.0 cm2/m2 for females at the cross-sectional area of the third lumbar vertebrae. Secondary outcomes of this study included the relationships between upper limb muscle thickness and biceps brachii muscle cross-sectional area, quadriceps femoris thickness, rectus femoris cross-sectional area. RESULTS: Among 64 patients assessed by ultrasound, 52 had CT examination records and were included in the analysis. The mean age was 70 ± 13 years, and the mean body mass index was 23.3 ± 4.2 kg/m2. Upper limb muscle thickness had the discriminative power to assess low muscularity at an area under the curve of 0.77 (95% CI [confidence interval], 0.63-0.91); the cutoff value (26.8 cm) had 84.6% sensitivity and 66.7% specificity. The upper limb muscle index had the discriminative power to assess low muscularity at an area under the curve of 0.80 (95% CI, 0.68-0.93); the cutoff value (9.9 mm/m2) had 76.9% sensitivity and 71.8% specificity. Upper limb muscle thickness was correlated with upper limb muscle cross-sectional area, quadriceps femoris muscle thickness, rectus femoris muscle cross-sectional area (r = 0.39-0.76, p < 0.01, n = 52). CONCLUSIONS: Ultrasound-based upper limb muscle thickness assessments can screen for low muscularity upon ICU admission.

Effects of Mobilization within 72 h of ICU Admission in Critically Ill Patients: An Updated Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Previous systematic review and meta-analysis indicates that rehabilitation within a week of intensive care unit (ICU) admission benefits physical function in critically ill patients. This updated systematic review and meta-analysis aim to clarify effects of initiating rehabilitation within 72 h of ICU admission on long-term physical, cognitive, and mental health. We systematically searched the MEDLINE, Cochrane Central Register of Controlled Trials, and Igaku Chuo Zasshi for randomized controlled trials (RCTs) between April 2019 and November 2022 to add to the previous review. Two investigators independently selected and extracted data. Pooled effect estimates for muscle strength, cognitive function, mental health after discharge, and adverse events were calculated. Evidence certainty was assessed via Grading of Recommendations, Assessment, Development, and Evaluations. Eleven RCTs were included in the meta-analysis. Early rehabilitation may improve muscle strength (three trials; standard mean difference [SMD], 0.16; 95% confidence interval [CI], -0.04-0.36) and cognitive function (two trials; SMD, 0.54; 95% CI, -0.13-1.20). Contrastingly, early mobilization showed limited impact on mental health or adverse events. In summary, initiating rehabilitation for critically ill patients within 72 h may improve physical and cognitive function to prevent post-intensive care syndrome without increasing adverse events. The effect on mental function remains uncertain.

Impact of the coronavirus disease 2019 (COVID-19) pandemic on the operational efficiency of emergency medical services and its association with out-of-hospital cardiac arrest survival rates: A population-based cohort study in Kobe, Japan.

Aim: To identify whether the coronavirus disease 2019 (COVID-19) pandemic affects the operational efficiency of emergency medical services (EMS) and the survival rate of out-of-hospital cardiac arrest (OHCA) in prehospital settings. Methods: We conducted a population-based cohort study in Kobe, Japan, between March 1, 2020, and September 31, 2022. In study 1, the operational efficiency of EMS, such as the total out-of-service time for ambulances, the daily occupancy rate of EMS, and response time, was compared between the pandemic and nonpandemic periods. In study 2, the impacts of the changes in EMS operational efficiency were investigated among patients with OHCA, with 1-month survival as the primary outcome and return of spontaneous circulation, 24-h survival, 1-week survival, and favorable neurological outcomes as the secondary outcomes. Logistic regression analysis was conducted to identify the factors associated with survival among patients with OHCA. Results: The total out-of-service time, occupancy rate, and response time significantly increased during the pandemic period (p < 0.001). The response time during the pandemic period increased significantly per pandemic wave. Regarding OHCA outcomes, 1-month survival rates during the pandemic period significantly decreased compared with those during the nonpandemic period (pandemic 3.7% vs. nonpandemic 5.7%; p < 0.01). Similarly, 24-h survival (9.9% vs. 12.8%), and favorable neurological outcomes significantly decreased during the pandemic period. In the logistic regression analysis, response time was associated with lower OHCA survival in all outcomes (p < 0.05). Conclusion: The COVID-19 pandemic has been associated with reduced operational efficiency of EMS and decreased OHCA survival rates. Further research is required to improve the efficiency of EMS and OHCA survival rates.

Effect of Neuromuscular Electrical Stimulation in Patients With Critical Illness: An Updated Systematic Review and Meta-Analysis of Randomized Controlled Trials.

OBJECTIVES: Neuromuscular electrical stimulation (NMES) is used in the rehabilitation of patients with critical illness. However, it is unclear whether NMES prevents ICU-acquired weakness (ICU-AW). For this purpose, we conducted an updated systematic review and meta-analysis. DATA SOURCES: We searched the MEDLINE, Cochrane Central Register of Controlled Trials, and Igaku Chuo Zasshi databases from April 2019 to November 2022 to identify new randomized controlled trials to the previous meta-analysis. STUDY SELECTION: We systematically searched the literature for all randomized controlled trials on the effect of NMES in patients with critical illness. DATA EXTRACTION: Two authors independently selected the studies and extracted data. They calculated the pooled effect estimates associated with the occurrence of ICU-AW and adverse events as primary outcomes and muscle mass change, muscle strength, length of ICU stay, mortality, and quality of life as secondary outcomes. The certainty of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation approach. DATA SYNTHESIS: Overall, eight studies were added to the previous 10 studies. Evidence suggests that the use of NMES reduces the occurrence of ICU-AW (six trials; risk ratio [RR], 0.48; 95% CI, 0.32-0.72); however, NMES may have little to no effect on pricking sensation in patients (eight trials; RR, 6.87; 95% CI, 0.84-56.50). NMES is likely to reduce the change in muscle mass (four trials; mean difference, -10.01; 95% CI, -15.54 to -4.48) and may increase muscle strength (six trials; standardized mean difference, 0.43; 95% CI, 0.19-0.68). Further, NMES may result in little to no difference in the length of ICU stay, and the evidence is uncertain about the effect on mortality and quality of life. CONCLUSIONS: This updated meta-analysis revealed that the use of NMES may result in a lower occurrence of ICU-AW in patients with critical illness, but its use may have little to no effect on pricking sensation in patients.

Current practice and barriers in the implementation of ultrasound-based assessment of muscle mass in Japan: A nationwide, web-based cross-sectional study.

Muscle mass is an important factor for surviving an illness. Ultrasound has gained increased attention as a muscle mass assessment method because of its noninvasiveness and portability. However, data on the frequency of ultrasound-based muscle mass assessment are limited, and there are some barriers to its implementation. Hence, a web-based cross-sectional survey was conducted on healthcare providers in Japan, which comprised four parts: 1) participant characteristics; 2) general muscle mass assessment; 3) ultrasound-based muscle mass assessment; and 4) the necessity of, interest in, and barriers to its implementation. Necessity and interest were assessed using an 11-point Likert scale, whereas barriers were assessed using a 5-point Likert scale, in which "Strongly agree" and "Agree" were counted for the analysis. Of the 1,058 responders, 1,026 participants, comprising 282 physicians, 489 physical therapists, 84 occupational therapists, 120 nurses, and 51 dieticians, were included in the analysis. In total, 93% of the participants were familiar with general muscle mass assessment, and 64% had conducted it. Ultrasound-based muscle mass assessment was performed by 21% of the participants. Necessity and interest scored 7 (6-8) and 8 (7-10), respectively for ultrasound-based muscle mass assessment. The barriers to its implementation included lack of relevant education (84%), limited staff (61%), and absence of fixed protocol (61%). Regardless of the necessity of and interest in ultrasound-based muscle mass assessment, it was only conducted by one-fifth of the healthcare providers, and the most important barrier to its implementation was lack of education.

Sepsis causes neutrophil infiltration in muscle leading to muscle atrophy and weakness in mice.

Background: Sepsis-induced muscle atrophy leads to prolonged physical dysfunction. Although the interaction of muscle atrophy and macrophage has been reported in sepsis, the role of neutrophils in muscle atrophy has not been thoroughly investigated. This study sought to investigate the long-term changes in muscle-localized neutrophils after sepsis induction and their possible role in sepsis. Methods: Sepsis was induced in seven-week-old male C57BL/6J mice 8-12 (cecal slurry [CS] model) via intraperitoneal injection of 1 mg/g cecal slurry. The percentage change in body weight and grip strength was evaluated. The tibialis anterior muscles were dissected for microscopic examination of the cross-sectional area of myofibers or Fluorescence-activated cell sorting (FACS) analysis of immune cells. These changes were evaluated in the following conditions: (1) Longitudinal change until day 61, (2) CS concentration-dependent change on day 14 at the low (0.3 mg/g), middle (1.0 mg/g), and high (2.0 mg/g) concentrations, and (3) CS mice on day 14 treated with an anti-Ly6G antibody that depletes neutrophils. Results: Body weight and grip strength were significantly lower in the CS model until day 61 (body weight: 123.1% ± 1.8% vs. 130.3% ± 2.5%, p = 0.04; grip strength: 104.5% ± 3.8% vs. 119.3% ± 5.3%, p = 0.04). Likewise, cross-sectional muscle area gradually decreased until day 61 from the CS induction (895.6 [606.0-1304.9] µm2 vs. 718.8 [536.2-937.0] µm2, p < 0.01). The number of muscle-localized neutrophils increased from 2.3 ± 0.6 cell/mg on day 0 to 22.2 ± 13.0 cell/mg on day 14, and decreased thereafter. In terms of CS concentration-dependent change, cross-sectional area was smaller (484.4 ± 221.2 vs. 825.8 ± 436.2 µm2 [p < 0.001]) and grip strength was lower (71.4% ± 12.8% vs. 116.3% ± 7.4%, p = 0.01) in the CS High group compared with the control, with increased neutrophils (p = 0.03). Ly6G-depleted mice demonstrated significant increase of muscle cross-sectional area and grip strength compared with control mice (p < 0.01). Conclusions: Sepsis causes infiltration of neutrophils in muscles, leading to muscle atrophy and weakness. Depletion of neutrophils in muscle reverses sepsis-induced muscle atrophy and weakness. These results suggest that neutrophils may play a critical role in sepsis-induced muscle atrophy and weakness.

Prevalence and Risk Factor Analysis of Post-Intensive Care Syndrome in Patients with COVID-19 Requiring Mechanical Ventilation: A Multicenter Prospective Observational Study.

INTRODUCTION: Post-intensive care syndrome (PICS) is an emerging problem in critically ill patients and the prevalence and risk factors are unclear in patients with severe coronavirus disease 2019 (COVID-19). This multicenter prospective observational study aimed to investigate the prevalence and risk factors of PICS in ventilated patients with COVID-19 after ICU discharge. METHODS: Questionnaires were administered twice in surviving patients with COVID-19 who had required mechanical ventilation, concerning Barthel Index, Short-Memory Questionnaire, and Hospital Anxiety and Depression Scale scores. The risk factors for PICS were examined using a multivariate logistic regression analysis. RESULTS: The first and second PICS surveys were obtained at 5.5 and 13.5 months (mean) after ICU discharge, with 251 and 209 patients completing the questionnaires and with a prevalence of PICS of 58.6% and 60.8%, respectively, along with the highest percentages of cognitive impairment. Delirium (with an odds ratio of (OR) 2.34, 95% CI 1.1-4.9, and p = 0.03) and the duration of mechanical ventilation (with an OR of 1.29, 95% CI 1.05-1.58, and p = 0.02) were independently identified as the risk factors for PICS in the first PICS survey. CONCLUSION: Approximately 60% of the ventilated patients with COVID-19 experienced persistent PICS, especially delirium, and required longer mechanical ventilation.

Prevalence and Long-Term Prognosis of Post-Intensive Care Syndrome after Sepsis: A Single-Center Prospective Observational Study.

Post-intensive care syndrome (PICS) comprises physical, mental, and cognitive disorders following a severe illness. The impact of PICS on long-term prognosis has not been fully investigated. This study aimed to: (1) clarify the frequency and clinical characteristics of PICS in sepsis patients and (2) explore the relationship between PICS occurrence and 2-year survival. Patients with sepsis admitted to intensive care unit were enrolled. Data on patient background; clinical information since admission; physical, mental, and cognitive impairments at 3-, 6-, and 12-months post-sepsis onset; 2-year survival; and cause of death were obtained from electronic medical records and telephonic interviews with patients and their families. At 3 months, comparisons of variables were undertaken in the PICS group and the non-PICS group. Among the 77 participants, the in-hospital mortality rate was 11% and the 2-year mortality rate was 52%. The frequencies of PICS at 3, 6, and 12 months were 70%, 60%, and 35%, respectively. The 2-year survival was lower in the PICS group than in the non-PICS group (54% vs. 94%, p < 0.01). More than half of the survivors had PICS at 3 and 6 months after sepsis. Among survivors with sepsis, those who developed PICS after 3 months had a lower 2-year survival.

Post-Intensive Care Syndrome-10 Years after Its Proposal and Future Directions.

With the development of intensive care medicine and the standardization of various therapeutic guidelines and education systems, mortality rates in critically ill patients have improved markedly [...].

Mobilization and Rehabilitation Practice in ICUs During the COVID-19 Pandemic.

BACKGROUND: Mobilization and acute rehabilitation are essential in the intensive care unit (ICU), with substantial evidence supporting their benefits. This study aimed to characterize ICU mobilization practices during the COVID-19 pandemic for patients with and without COVID-19. METHODS: This was a secondary analysis of an international point prevalence study. All ICUs across the world were eligible to participate and were required to enroll all patients in each ICU on the survey date, 27 January 2021. The primary outcome was the achievement of mobilization at the level of sitting over the edge of the bed. Independent factors associated with mobilization, including COVID-19 infection, were analyzed by multivariable analysis. RESULTS: A total of 135 ICUs in 33 countries participated, for inclusion of 1229 patients. Among patients who were not receiving mechanical ventilation (MV), those with COVID-19 infection were mobilized more than those without COVID-19 (60% vs. 34%, p < 0.001). Among patients who were receiving MV, mobilization was low in both groups (7% vs. 9%, p = .56). These findings were consistent irrespective of ICU length of stay. Multivariable analysis showed that COVID-19 infection was associated with achievement of mobilization in patients without (adjusted odds ratio [aOR] = 4.48, 95% confidence interval [CI] = 2.71-7.42) and with MV (aOR = 2.13, 95% CI = 1.00-4.51). Factors that prevented mobilization were prone positioning in patients without MV and continuous use of neuromuscular blockade and sedation agents in patients with MV, whereas facilitating factors were the presence of targets/goals in both groups. CONCLUSION: Mobilization rates for ICU patients across the globe are severely low, with the greatest immobility observed in mechanically ventilated patients. Although COVID-19 is not an independent barrier to the mobilization of patients with or without MV, this study has highlighted the current lack of mobility practice for all ICU patients during the COVID-19 pandemic.(299 words).

Relation between nutrition therapy in the acute phase and outcomes of ventilated patients with COVID-19 infection: a multicenter prospective observational study.

BACKGROUND: Optimal nutrition therapy has not yet been established for the acute phase of severe coronavirus disease 2019 (COVID-19) infection. OBJECTIVES: We aimed to examine the effects of nutrition delivery in the acute phase on mortality and the long-term outcomes of post-intensive care syndrome (PICS). METHODS: A multicenter prospective study was conducted on adult patients with COVID-19 infection requiring mechanical ventilation during an intensive care unit (ICU) stay. Daily total energy (kcal/kg) and protein (g/kg) deliveries in the first week of the ICU stay were calculated. The questionnaire for PICS evaluation was mailed within a median of 6 mo after hospital discharge. The primary outcome was in-hospital mortality, and secondary outcomes were the PICS components of physical impairment, cognitive dysfunction, and mental illness. RESULTS: Among 414 eligible patients, 297 who received mechanical ventilation for 7 d or longer were examined. PICS was evaluated in 175 patients among them. High protein delivery on days 4-7 correlated with a low in-hospital mortality rate. In contrast, high protein delivery on days 1-3 correlated with physical impairment. A multivariate logistic regression analysis adjusted for age, sex, BMI, and severity revealed that average energy and protein deliveries on days 4-7 correlated with decreased in-hospital mortality (OR: 0.94; 95% CI: 0.89, 0.99; P = 0.013 and OR: 0.40; 95% CI: 0.17, 0.93; P = 0.031, respectively). Nutrition delivery did not correlate with PICS outcomes after adjustments. In the multivariate regression using a restricted cubic spline model, in-hospital mortality monotonically decreased with increases in average nutrition delivery on days 4-7. CONCLUSIONS: In patents with COVID-19 on mechanical ventilation for ≥7 d, nutrition delivery in the late period of the acute phase was monotonically associated with a decrease in in-hospital mortality. Adequate protein delivery is needed on days 4-7.This trial was registered at https://www.umin.ac.jp as UMIN000041276.

C188-9, a specific inhibitor of STAT3 signaling, prevents thermal burn-induced skeletal muscle wasting in mice.

Burn injury is the leading cause of death and disability worldwide and places a tremendous economic burden on society. Systemic inflammatory responses induced by thermal burn injury can cause muscle wasting, a severe involuntary loss of skeletal muscle that adversely affects the survival and functional outcomes of these patients. Currently, no pharmacological interventions are available for the treatment of thermal burn-induced skeletal muscle wasting. Elevated levels of inflammatory cytokines, such as interleukin-6 (IL-6), are important hallmarks of severe burn injury. The levels of signal transducer and activator of transcription 3 (STAT3)-a downstream component of IL-6 inflammatory signaling-are elevated with muscle wasting in various pro-catabolic conditions, and STAT3 has been implicated in the regulation of skeletal muscle atrophy. Here, we tested the effects of the STAT3-specific signaling inhibitor C188-9 on thermal burn injury-induced skeletal muscle wasting in vivo and on C2C12 myotube atrophy in vitro after the administration of plasma from burn model mice. In mice, thermal burn injury severity dependently increased IL-6 in the plasma and tibialis anterior muscles and activated the STAT3 (increased ratio of phospho-STAT3/STAT3) and ubiquitin-proteasome proteolytic pathways (increased Atrogin-1/MAFbx and MuRF1). These effects resulted in skeletal muscle atrophy and reduced grip strength. In murine C2C12 myotubes, plasma from burn mice activated the same inflammatory and proteolytic pathways, leading to myotube atrophy. In mice with burn injury, the intraperitoneal injection of C188-9 (50 mg/kg) reduced activation of the STAT3 and ubiquitin-proteasome proteolytic pathways, reversed skeletal muscle atrophy, and increased grip strength. Similarly, pretreatment of murine C2C12 myotubes with C188-9 (10 µM) reduced activation of the same inflammatory and proteolytic pathways, and ameliorated myotube atrophy induced by plasma taken from burn model mice. Collectively, these results indicate that pharmacological inhibition of STAT3 signaling may be a novel therapeutic strategy for thermal burn-induced skeletal muscle wasting.