Role of mesenchymal stem cells in sepsis and their therapeutic potential in sepsis­associated myopathy (Review).

Sepsis­induced myopathy (SIM) is one of the leading causes of death in critically ill patients. SIM mainly involves the respiratory and skeletal muscles of patients, resulting in an increased risk of lung infection, aggravated respiratory failure, and prolonged mechanical ventilation and hospital stay. SIM is also an independent risk factor associated with increased mortality in critically ill patients. At present, no effective treatment for SIM has yet been established. However, mesenchymal stem cells (MSCs) have emerged as a promising therapeutic approach and have been utilized in the treatment of various clinical conditions. A significant body of basic and clinical research supports the efficacy of MSCs in managing sepsis and muscle­related diseases. This literature review aims to explore the relationship between MSCs and sepsis, as well as their impact on skeletal muscle­associated diseases. Additionally, the present review discusses the potential mechanisms and therapeutic benefits of MSCs in the context of SIM.

PEI/MMNs@LNA-542 nanoparticles alleviate ICU-acquired weakness through targeted autophagy inhibition and mitochondrial protection.

Intensive care unit-acquired weakness (ICU-AW) is prevalent in critical care, with limited treatment options. Certain microRNAs, like miR-542, are highly expressed in ICU-AW patients. This study investigates the regulatory role and mechanisms of miR-542 in ICU-AW and explores the clinical potential of miR-542 inhibitors. ICU-AW models were established in C57BL/6 mice through cecal ligation and puncture (CLP) and in mouse C2C12 myoblasts through TNF-α treatment. In vivo experiments demonstrated decreased muscle strength, muscle fiber atrophy, widened intercellular spaces, and increased miR-542-3p/5p expression in ICU-AW mice model. In vitro experiments indicated suppressed ATG5, ATG7 and LC3II/I, elevated MDA and ROS levels, decreased SOD levels, and reduced MMP in the model group. Similar to animal experiments, the expression of miR-542-3p/5p was upregulated. Gel electrophoresis explored the binding of polyethyleneimine/mesoporous silica nanoparticles (PEI/MMNs) to locked nucleic acid (LNA) miR-542 inhibitor (LNA-542). PEI/MMNs@LNA-542 with positive charge (3.03 ± 0.363 mV) and narrow size (206.94 ± 6.19 nm) were characterized. Immunofluorescence indicated significant internalization with no apparent cytotoxicity. Biological activity, examined through intraperitoneal injection, showed that PEI/MMNs@LNA-542 alleviated muscle strength decline, restored fiber damage, and recovered mitochondrial injury in mice. In conclusion, PEI/MMNs nanoparticles effectively delivered LNA-542, targeting ATG5 to inhibit autophagy and alleviate mitochondrial damage, thereby improving ICU-AW.

Macrophages modulate skeletal muscle wasting and recovery in acute lung injury in mice.

Skeletal muscle dysfunction in critical illnesses leaves survivors weak and functionally impaired. Macrophages infiltrate muscles; however, their functional role is unclear. We aim to examine muscle leukocyte composition and the effect of macrophages on muscle mass and function in the murine acute lung injury (ALI)-associated skeletal muscle wasting model. We performed flow cytometry of hindlimb muscle to identify myeloid cells pre-injury and time points up to 29 days after intratracheal lipopolysaccharide ALI. We evaluated muscle force and morphometrics after systemic and intramuscular clodronate-induced macrophage depletions between peak lung injury and recovery (day 5-6) versus vehicle control. Our results show muscle leukocytes changed over ALI course with day 3 neutrophil infiltration (130.5 ± 95.6cells/mg control to 236.3 ± 70.6cells/mg day 3) and increased day 10 monocyte abundance (5.0 ± 3.4%CD45+CD11b+ day 3 to 14.0 ± 2.6%CD45+CD11b+ day 10, p = 0.005). Although macrophage count did not significantly change, pro-inflammatory (27.0 ± 7.2% day 3 to 7.2 ± 3.8% day 10, p = 0.02) and anti-inflammatory (30.5 ± 11.1% day 3 to 52.7 ± 9.7% day 10, p = 0.09) surface marker expression changed over the course of ALI. Macrophage depletion following peak lung injury increased muscle mass and force generation. These data suggest muscle macrophages beyond peak lung injury limit or delay muscle recovery. Targeting macrophages could augment muscle recovery following lung injury.

Comparison between Effect of Indirect Calorimetry vs Weight-based Equation (25 kcal/kg/day)-guided Nutrition on Quadriceps Muscle Thickness as Assessed by Bedside Ultrasonography in Medical Intensive Care Unit Patients: A Randomized Clinical Trial.

Aim and background: Sarcopenia is a substantial contributor to intensive care unit (ICU)-acquired weakness and is associated with significant short- and long-term outcomes. It can, however, be mitigated by providing appropriate nutrition. Indirect calorimetry (IC) is believed to be the gold standard in determining caloric targets in the dynamic environment of critical illness. We conducted this study to compare the effect of IC vs weight-based (25 kcal/kg/day) feeding on quadriceps muscle thickness (QMT) by ultrasound in critically ill patients. Materials and methods: A prospective study was conducted on 60 mechanically ventilated patients randomized to two groups [weight-based equation (WBE) group or the IC group] in medical ICU after obtaining institutional ethics committee approval, and fed accordingly. The right QMT measurement using ultrasound and caloric targets were documented on day 1, 3 and 7 and analyzed statistically. The IC readings were obtained from the metabolic cart E-COVX ModuleTM. Results: The baseline demographics, APACHE-II, NUTRIC score, and SOFA scores on day 1, 3, and 7 were comparable between the two groups. The resting energy expenditure (REE) obtained in the IC group was significantly less than the WBE energy targets and the former were fed with significantly less calories. A significantly less percent reduction of QMT in the IC group compared with the WBE group was observed from day 1 to day 3, day 3 to day 7, and day 1 to day 7. Conclusion: From our study, we conclude that IC-REE-based nutrition is associated with lesser reduction in QMT and lesser calories fed in critically ill mechanically ventilated patients compared from WBE. CTRI registration-CTRI/2023/01/049119. How to cite this article: Chandrasekaran A, Pal D, Harne R, Patel SJ, Jagadeesh KN, Pachisia AV, et al. Comparison between Effect of Indirect Calorimetry vs Weight-based Equation (25 kcal/kg/day)-guided Nutrition on Quadriceps Muscle Thickness as Assessed by Bedside Ultrasonography in Medical Intensive Care Unit Patients: A Randomized Clinical Trial. Indian J Crit Care Med 2024;28(6):587-594.

Advancing critical care recovery: The pivotal role of machine learning in early detection of intensive care unit-acquired weakness.

This editorial explores the significant challenge of intensive care unit-acquired weakness (ICU-AW), a prevalent condition affecting critically ill patients, characterized by profound muscle weakness and complicating patient recovery. Highlighting the paradox of modern medical advances, it emphasizes the urgent need for early identification and intervention to mitigate ICU-AW's impact. Innovatively, the study by Wang et al is showcased for employing a multilayer perceptron neural network model, achieving high accuracy in predicting ICU-AW risk. This advancement underscores the potential of neural network models in enhancing patient care but also calls for continued research to address limitations and improve model applicability. The editorial advocates for the development and validation of sophisticated predictive tools, aiming for personalized care strategies to reduce ICU-AW incidence and severity, ultimately improving patient outcomes in critical care settings.

Intensive care unit-acquired weakness - preventive, and therapeutic aspects; future directions and special focus on lung transplantation.

In this editorial, comments are made on an interesting article in the recent issue of the World Journal of Clinical Cases by Wang and Long. The authors describe the use of neural network model to identify risk factors for the development of intensive care unit (ICU)-acquired weakness. This condition has now become common with an increasing number of patients treated in ICUs and continues to be a source of morbidity and mortality. Despite identification of certain risk factors and corrective measures thereof, lacunae still exist in our understanding of this clinical entity. Numerous possible pathogenetic mechanisms at a molecular level have been described and these continue to be increasing. The amount of retrievable data for analysis from the ICU patients for study can be huge and enormous. Machine learning techniques to identify patterns in vast amounts of data are well known and may well provide pointers to bridge the knowledge gap in this condition. This editorial discusses the current knowledge of the condition including pathogenesis, diagnosis, risk factors, preventive measures, and therapy. Furthermore, it looks specifically at ICU acquired weakness in recipients of lung transplantation, because - unlike other solid organ transplants- muscular strength plays a vital role in the preservation and survival of the transplanted lung. Lungs differ from other solid organ transplants in that the proper function of the allograft is dependent on muscle function. Muscular weakness especially diaphragmatic weakness may lead to prolonged ventilation which has deleterious effects on the transplanted lung - ranging from ventilator associated pneumonia to bronchial anastomotic complications due to prolonged positive pressure on the anastomosis.

Anabolic Strategies for ICU-Acquired Weakness. What Can We Learn from Bodybuilders?

The study aimed to show the potential clinical application of supplements used among sportsmen for patients suffering from Intensive Care Unit-acquired Weakness (ICUAW) treatment. ICUAW is a common complication affecting approximately 40% of critically ill patients, often leading to long-term functional disability. ICUAW comprises critical illness polyneuropathy, critical illness myopathy, or a combination of both, such as critical illness polyneuromyopathy. Muscle degeneration begins shortly after the initiation of mechanical ventilation and persists post-ICU discharge until proteolysis and autophagy processes normalize. Several factors, including prolonged bedrest and muscle electrical silencing, contribute to muscle weakness, resulting from an imbalance between protein degradation and synthesis. ICUAW is associated with tissue hypoxia, oxidative stress, insulin resistance, reduced glucose uptake, lower adenosine triphosphate (ATP) formation, mitochondrial dysfunction, and increased free-radical production. Several well-studied dietary supplements and pharmaceuticals commonly used by athletes are proven to prevent the aforementioned mechanisms or aid in muscle building, regeneration, and maintenance. While there is no standardized treatment to prevent the occurrence of ICUAW, nutritional interventions have demonstrated the potential for its mitigation. The use of ergogenic substances, popular among muscle-building sociates, may offer potential benefits in preventing muscle loss and aiding recovery based on their work mechanisms.

Unveiling significant risk factors for intensive care unit-acquired weakness: Advancing preventive care.

In this editorial, we discuss an article titled, "Significant risk factors for intensive care unit-acquired weakness: A processing strategy based on repeated machine learning," published in a recent issue of the World Journal of Clinical Cases. Intensive care unit-acquired weakness (ICU-AW) is a debilitating condition that affects critically ill patients, with significant implications for patient outcomes and their quality of life. This study explored the use of artificial intelligence and machine learning techniques to predict ICU-AW occurrence and identify key risk factors. Data from a cohort of 1063 adult intensive care unit (ICU) patients were analyzed, with a particular emphasis on variables such as duration of ICU stay, duration of mechanical ventilation, doses of sedatives and vasopressors, and underlying comorbidities. A multilayer perceptron neural network model was developed, which exhibited a remarkable impressive prediction accuracy of 86.2% on the training set and 85.5% on the test set. The study highlights the importance of early prediction and intervention in mitigating ICU-AW risk and improving patient outcomes.

Machine learning insights on intensive care unit-acquired weakness.

Intensive care unit-acquired weakness (ICU-AW) significantly hampers patient recovery and increases morbidity. With the absence of established preventive strategies, this study utilizes advanced machine learning methodologies to unearth key predictors of ICU-AW. Employing a sophisticated multilayer perceptron neural network, the research methodically assesses the predictive power for ICU-AW, pinpointing the length of ICU stay and duration of mechanical ventilation as pivotal risk factors. The findings advocate for minimizing these elements as a preventive approach, offering a novel perspective on combating ICU-AW. This research illuminates critical risk factors and lays the groundwork for future explorations into effective prevention and intervention strategies.

Increasing role of post-intensive care syndrome in quality of life of intensive care unit survivors.

In this editorial we comment on the detrimental consequences that post-intensive care syndrome (PICS) has in the quality of life of intensive care unit (ICU) survivors, highlighting the importance of early onset of multidisciplinary rehabilitation from within the ICU. Although, the syndrome was identified and well described early in 2012, more awareness has been raised on the long-term PICS related health problems by the increased number of coronavirus disease 2019 ICU survivors. It is well outlined that the syndrome affects both the patient and the family and is described as the appearance or worsening of impairment in physical, cognitive, or mental health as consequence of critical illness. PICS was described in order: (1) To raise awareness among clinicians, researchers, even the society; (2) to highlight the need for a multilevel screening of these patients that starts from within the ICU and continues after discharge; (3) to present preventive strategies; and (4) to offer guidelines in terms of rehabilitation. An early multidisciplinary approach is the key element form minimizing the incidence of PICS and its consequences in health related quality of life of both survivors and their families.

Corrigendum: Survival outcomes and mobilization during venovenous extracorporeal membrane oxygenation: a retrospective cohort study.

[This corrects the article DOI: 10.3389/fmed.2023.1271540.].

Pioneering role of machine learning in unveiling intensive care unit-acquired weakness.

In the research published in the World Journal of Clinical Cases, Wang and Long conducted a quantitative analysis to delineate the risk factors for intensive care unit-acquired weakness (ICU-AW) utilizing advanced machine learning methodologies. The study employed a multilayer perceptron neural network to accurately predict the incidence of ICU-AW, focusing on critical variables such as ICU stay duration and mechanical ventilation. This research marks a significant advancement in applying machine learning to clinical diagnostics, offering a new paradigm for predictive medicine in critical care. It underscores the importance of integrating artificial intelligence technologies in clinical practice to enhance patient management strategies and calls for interdisciplinary collaboration to drive innovation in healthcare.

Predicting intensive care unit-acquired weakness: A multilayer perceptron neural network approach.

In this editorial, we comment on the article by Wang and Long, published in a recent issue of the World Journal of Clinical Cases. The article addresses the challenge of predicting intensive care unit-acquired weakness (ICUAW), a neuromuscular disorder affecting critically ill patients, by employing a novel processing strategy based on repeated machine learning. The editorial presents a dataset comprising clinical, demographic, and laboratory variables from intensive care unit (ICU) patients and employs a multilayer perceptron neural network model to predict ICUAW. The authors also performed a feature importance analysis to identify the most relevant risk factors for ICUAW. This editorial contributes to the growing body of literature on predictive modeling in critical care, offering insights into the potential of machine learning approaches to improve patient outcomes and guide clinical decision-making in the ICU setting.

Significant risk factors for intensive care unit-acquired weakness: A processing strategy based on repeated machine learning.

BACKGROUND: Intensive care unit-acquired weakness (ICU-AW) is a common complication that significantly impacts the patient's recovery process, even leading to adverse outcomes. Currently, there is a lack of effective preventive measures. AIM: To identify significant risk factors for ICU-AW through iterative machine learning techniques and offer recommendations for its prevention and treatment. METHODS: Patients were categorized into ICU-AW and non-ICU-AW groups on the 14th day post-ICU admission. Relevant data from the initial 14 d of ICU stay, such as age, comorbidities, sedative dosage, vasopressor dosage, duration of mechanical ventilation, length of ICU stay, and rehabilitation therapy, were gathered. The relationships between these variables and ICU-AW were examined. Utilizing iterative machine learning techniques, a multilayer perceptron neural network model was developed, and its predictive performance for ICU-AW was assessed using the receiver operating characteristic curve. RESULTS: Within the ICU-AW group, age, duration of mechanical ventilation, lorazepam dosage, adrenaline dosage, and length of ICU stay were significantly higher than in the non-ICU-AW group. Additionally, sepsis, multiple organ dysfunction syndrome, hypoalbuminemia, acute heart failure, respiratory failure, acute kidney injury, anemia, stress-related gastrointestinal bleeding, shock, hypertension, coronary artery disease, malignant tumors, and rehabilitation therapy ratios were significantly higher in the ICU-AW group, demonstrating statistical significance. The most influential factors contributing to ICU-AW were identified as the length of ICU stay (100.0%) and the duration of mechanical ventilation (54.9%). The neural network model predicted ICU-AW with an area under the curve of 0.941, sensitivity of 92.2%, and specificity of 82.7%. CONCLUSION: The main factors influencing ICU-AW are the length of ICU stay and the duration of mechanical ventilation. A primary preventive strategy, when feasible, involves minimizing both ICU stay and mechanical ventilation duration.

Effects of acute phase intensive electrical muscle stimulation in COVID-19 patients requiring invasive mechanical ventilation: an observational case-control study.

We investigated the effects of acute-phase intensive electrical muscle stimulation (EMS) on physical function in COVID-19 patients with respiratory failure requiring invasive mechanical ventilation (IMV) in the intensive care unit (ICU). Consecutive COVID-19 patients requiring IMV admitted to a university hospital ICU between January and April 2022 (EMS therapy group) or between March and September 2021 (age-matched historical control group) were included in this retrospective observational case-control study. EMS was applied to both upper and lower limb muscles for up to 2 weeks in the EMS therapy group. The study population consisted of 16 patients undergoing EMS therapy and 16 age-matched historical controls (median age, 71 years; 81.2% male). The mean period until initiation of EMS therapy after ICU admission was 3.2 ± 1.4 days. The EMS therapy group completed a mean of 6.2 ± 3.7 EMS sessions, and no adverse events occurred. There were no significant differences between the two groups in Medical Research Council sum score (51 vs. 53 points, respectively; P = 0.439) or ICU mobility scale at ICU discharge. Addition of upper and lower limb muscle EMS therapy to an early rehabilitation program did not result in improved physical function at ICU discharge in severe COVID-19 patients.

Achievement of adequate nutrition contributes to maintaining the skeletal muscle area in patients with sepsis undergoing early mobilization: a retrospective observational study.

BACKGROUND: The onset of muscle loss in critically ill patients, known as intensive care unit-acquired weakness (ICU-AW), worsens their outcomes. Preventing muscle loss, which begins in the early phase of critical illness, is crucial in patient care. Adequate nutrition management may contribute to maintaining muscles; however, its evidence in patients with sepsis is insufficient. This study aimed to analyze the association between energy achievement rate in the first 7-days of critical care and muscle area changes evaluated by computed tomography (CT). METHODS: This was a retrospective observational study. Patients with sepsis admitted to the intensive care (ICU) of a tertiary care hospital in Japan were included. They were divided into three groups according to tertiles of the first 7-day energy achievement rate calculated using administered energy doses and basement energy expenditure. Skeletal muscle area (SMA) and changes in SMA were determined by CT on ICU admission and within days 7-10 of ICU admission. SMA maintenance was defined as SMA change ≥ 100%. Logistic regression analyses were performed to analyze the association of energy achievement rate with SMA changes (primary outcome) and in-hospital 28-day mortality (secondary outcome). RESULTS: Patients (n = 93) were classified into low, middle, and high groups according to their 7-day energy achievement rate (median rates, 16.8%, 38.8%, and 73.4%, respectively). The CT scans showed that SMA decreased between the CT scans in the low and middle groups, whereas it was maintained in the high group (median changes, -8.5%, -11.7%, and 2.8%, respectively). Univariate and multivariate logistic regression analyses showed that high energy achievement rate was significantly associated with SMA maintenance (reference, middle energy achieved group; univariate, odds ratio [95% confidence interval] 6.23 [2.04-19.10], P = 0.0013; multivariate, odds ratio [95% confidence interval] 5.92 [1.90-18.40], P = 0.0021). There was no significant difference in the association between energy achievement rate and mortality among the three groups. CONCLUSIONS: Our study found that a fulfillment of energy achievement in the first 7 days of hospitalization was associated with maintenance of muscle area. Thus, satisfying adequate energy should be considered even in patients with sepsis.

Early Mobilization and Rehabilitation of Critically-Ill Patients.

Post-intensive care unit (ICU) syndrome may occur after ICU treatment and includes ICU-acquired weakness (ICU-AW), cognitive decline, and mental problems. ICU-AW is muscle weakness in patients treated in the ICU and is affected by the period of mechanical ventilation. Diaphragmatic weakness may also occur because of respiratory muscle unloading using mechanical ventilators. ICU-AW is an independent predictor of mortality and is associated with longer duration of mechanical ventilation and hospital stay. Diaphragm weakness is also associated with poor outcomes. Therefore, pulmonary rehabilitation with early mobilization and respiratory muscle training is necessary in the ICU after appropriate patient screening and evaluation and can improve ICU-related muscle weakness and functional deterioration.

Intensive care unit-acquired weakness: Recent insights.

Intensive care unit-acquired weakness (ICU-AW) is a common complication in critically ill patients and is associated with a variety of adverse outcomes. These include the need for prolonged mechanical ventilation and ICU stay; higher ICU, in-hospital, and 1-year mortality; and increased in-hospital costs. ICU-AW is associated with multiple risk factors including age, underlying disease, severity of illness, organ failure, sepsis, immobilization, receipt of mechanical ventilation, and other factors related to critical care. The pathological mechanism of ICU-AW remains unclear and may be considerably varied. This review aimed to evaluate recent insights into ICU-AW from several aspects including risk factors, pathophysiology, diagnosis, and treatment strategies; this provides new perspectives for future research.

A Predictive Nomogram for Intensive Care-Acquired Weakness after Cardiopulmonary Bypass.

PURPOSE: Intensive care unit-acquired weakness (ICUAW) affects patient prognosis after cardiopulmonary bypass (CPB) surgery, but its risk factors remain unclear. We investigated these risk factors and developed a nomogram for predicting ICUAW after CPB. METHODS: Baseline characteristics, preoperative laboratory data, and intra- and postoperative variables of 473 patients after CPB were determined in this prospective cohort study. Lower limb muscles on bedside ultrasound images were compared 1 day before and 7 days after CPB. Risk factors were assessed using logistic regression models. RESULTS: Approximately 50.95% of the patients developed ICUAW after CPB. The body mass index (BMI), New York Heart Association (NYHA) class, lactate, albumin, aortic clamping time, operation time, and acute physiological and chronic health evaluation II were determined as independent risk factors. The average absolute error of coincidence was 0.019; the area under the curve, sensitivity, and specificity were 0.811, 0.727, and 0.733, respectively, for the predictive nomogram. CONCLUSION: A high BMI, poor NYHA class, preoperative high serum lactate, low serum albumin, long surgical duration, aortic clamping, and high acute physiological and chronic health evaluation II score are risk factors for ICUAW after CPB. This robust and easy-to-use nomogram was developed for clinical decision-making.

Effect of neuromuscular electrical stimulation and early physical activity on ICU-acquired weakness in mechanically ventilated patients: A randomized controlled trial.

BACKGROUND: Intensive care unit-acquired weakness (ICU-AW) is common in critically ill patients and increases the duration of mechanical ventilation (MV) and weaning time. Early mobilization, range of motion (ROM) exercises, and neuromuscular electrical stimulation (NMES) can prevent ICU-AW by maintaining muscle mass. However, studies highlighting the effects of combining NMES with early physical activity in ICU patients are limited. AIM: To evaluate the effect of NMES and early physical activity on ICU-AW in mechanically ventilated patients. DESIGN: A single-blinded randomized controlled trial was conducted in Alexandria, Egypt. METHOD: Patients were randomly assigned to one of four groups: NMES, ROM, combined therapy (ROM + NMES), or conventional care (control group). The Medical Research Council (MRC) scale was used to assess the ICU-AW for the study patients over a 7-day period. The duration of the patient's MV and ICU stays were recorded. RESULTS: Of the 180 patients who were assessed for eligibility, 124 were randomly assigned to one of four groups: 32 patients in ROM exercises, 30 in NMES, 31 in combined therapy (ROM + NMES), and 31 in the control group. On day 7, ROM + NMES and NMES groups showed higher MRC scores than ROM and control groups (50.37 ± 2.34, 49.77 ± 2.19, 44.97 ± 3.61, and 41.10 ± 3.84, respectively). ANOVA test results indicated significant differences (p < .001) across the four groups. ICU-AW occurred in 0% of the ROM + NMES group, 60% of the ROM group, 13% of the NMES group, and 100% of the control group (p < .001). The MV duration (in days) in the ROM + NMES group was shorter (12.80 ± 3.800) than in the ROM, NMES, or control groups (21.80 ± 4.460, 18.73 ± 4.748, and 20.70 ± 3.932, respectively). ICU-LOS was shorter in the ROM + NMES group (17.43 ± 3.17 days) compared with the ROM group (22.53 ± 4.51 days), the NMES group (21.10 ± 5.0 days), and the control group (21.50 ± 4.42 days) with significant differences (p < .001) between the four groups. CONCLUSION: Daily sessions of NMES and early physical activity were well tolerated, preserved muscle strength, prevented ICU-AW, and decreased the duration of the MV and ICU stay. RELEVANCE TO CLINICAL PRACTICE: The findings of this study support the use of NMES and early physical exercises by critical care nurses as part of routine care for critically ill patients.