Survivorship after critical illness is an increasingly important health-care concern as ICU use continues to increase while ICU mortality is decreasing. Survivors of critical illness experience marked disability and impairments in physical and cognitive function that persist for years after their initial ICU stay. Newfound impairment is associated with increased health-care costs and use, reductions in health-related quality of life, and prolonged unemployment. Weakness, critical illness neuropathy and/or myopathy, and muscle atrophy are common in patients who are critically ill, with up to 80% of patients admitted to the ICU developing some form of neuromuscular dysfunction. ICU-acquired weakness (ICUAW) is associated with longer durations of mechanical ventilation and hospitalization, along with greater functional impairment for survivors. Although there is increasing recognition of ICUAW as a clinical entity, significant knowledge gaps exist concerning identifying patients at high risk for its development and understanding its role in long-term outcomes after critical illness. This review addresses the epidemiologic and pathophysiologic aspects of ICUAW; highlights the diagnostic challenges associated with its diagnosis in patients who are critically ill; and proposes, to our knowledge, a novel strategy for identifying ICUAW.Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

Critically ill patients often acquire neuropathy and/or myopathy labeled ICU-acquired weakness. The current insights into incidence, pathophysiology, diagnostic tools, risk factors, short- and long-term consequences and management of ICU-acquired weakness are narratively reviewed. PubMed was searched for combinations of "neuropathy", "myopathy", "neuromyopathy", or "weakness" with "critical illness", "critically ill", "ICU", "PICU", "sepsis" or "burn". ICU-acquired weakness affects limb and respiratory muscles with a widely varying prevalence depending on the study population. Pathophysiology remains incompletely understood but comprises complex structural/functional alterations within myofibers and neurons. Clinical and electrophysiological tools are used for diagnosis, each with advantages and limitations. Risk factors include age, weight, comorbidities, illness severity, organ failure, exposure to drugs negatively affecting myofibers and neurons, immobility and other intensive care-related factors. ICU-acquired weakness increases risk of in-ICU, in-hospital and long-term mortality, duration of mechanical ventilation and of hospitalization and augments healthcare-related costs, increases likelihood of prolonged care in rehabilitation centers and reduces physical function and quality of life in the long term. RCTs have shown preventive impact of avoiding hyperglycemia, of omitting early parenteral nutrition use and of minimizing sedation. Results of studies investigating the impact of early mobilization, neuromuscular electrical stimulation and of pharmacological interventions were inconsistent, with recent systematic reviews/meta-analyses revealing no or only low-quality evidence for benefit. ICU-acquired weakness predisposes to adverse short- and long-term outcomes. Only a few preventive, but no therapeutic, strategies exist. Further mechanistic research is needed to identify new targets for interventions to be tested in adequately powered RCTs.

To investigate the effects of early standardized enteral nutrition (EN) on the cross-sectional area of erector spine muscle (ESMcsa), plasma growth differentiation factor-15 (GDF-15), and 28-day mortality of acute exacerbation of chronic obstructive pulmonary disease (AECOPD) patients with invasive mechanical ventilation (MV).A total of 97 AECOPD patients with invasive MV were screened in the ICUs of the First People's Hospital of Lianyungang. The conventional EN group (stage I) and early standardized EN group (stage II) included 46 and 51 patients, respectively. ESMcsa loss and GDF-15 levels on days 1 and 7 of ICU admission and 28-day survival rates were analyzed.On day 7, the ESMcsa of the early standardized EN group was significantly higher than that of the conventional EN group, while the plasma GDF-15 levels were significantly lower than those in the conventional EN group (ESMcsa: 28.426±6.130 cm vs. 25.205±6.127 cm; GDF-15: 1661.608±558.820 pg/mL vs. 2541.000±634.845 pg/mL; all <0.001]. The 28-day survival rates of the patients in the early standardized EN group and conventional EN group were 80.40% and 73.90%, respectively (=0.406).ESMcsa loss in AECOPD patients with MV was correlated with GDF-15 levels, both of which indicated acute muscular atrophy and skeletal muscle dysfunction. Early standardized EN may prevent acute muscle loss and intensive care unit-acquired weakness (ICU-AW) in AECOPD patients.Copyright: © World Journal of Emergency Medicine.

Intensive care unit-acquired weakness (ICU-AW; ICD-10 Code: G72.81) is a syndrome of generalized weakness described as clinically detectable weakness in critically ill patients with no other credible cause. The risk factors for ICU-AW include hyperglycemia, parenteral nutrition, vasoactive drugs, neuromuscular blocking agents, corticosteroids, sedatives, some antibiotics, immobilization, the disease severity, septicemia and systemic inflammatory response syndrome, multiorgan failure, prolonged mechanical ventilation (MV), high lactate levels, older age, female sex, and pre-existing systemic morbidities. There is a definite association between the duration of ICU stay and MV with ICU-AW. However, the interpretation that these are modifiable risk factors influencing ICU-AW, appears to be flawed, because the relationship between longer ICU stays and MV with ICU-AW is reciprocal and cannot yield clinically meaningful strategies for the prevention of ICU-AW. Prevention strategies must be based on other risk factors. Large multicentric randomized controlled trials as well as meta-analysis of such studies can be a more useful approach towards determining the influence of these risk factors on the occurrence of ICU-AW in different populations.©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.

While sepsis mortality is reducing in developed countries due to advances in intensive care medicine, morbidity is increasing due to aging and obesity. ICU-acquired weakness (ICU-AW) is a respiratory and limb muscle weakness experienced by many sepsis survivors and is present in 50-75% of sepsis patients. ICU-AW can persist for several years, making reintegration of sepsis survivors difficult and leading to a secondary decrease in long-term survival. Exposure of septic patients to multiple muscle-damaging factors during ICU admission, including hyperglycemia, immobility, mechanical ventilation, administration of muscle relaxants, and administration of steroidal anti-inflammatory drugs, may compound the hyper cytokine, hyper nitric oxide, and hyper oxidative conditions, leading to the development of ICU-AW. However, the pathogenesis of ICU-AW remains unclear, and the pathophysiology of ICU-AW awaits further elucidation to develop therapeutic strategies. Recent ICU-AW studies have also revealed that skeletal muscle itself is a key organ in the inflammatory response and metabolic abnormalities in sepsis. In this article, we review the pathophysiology of skeletal muscle in sepsis and international trends in the development of therapeutic agents based on our research results.

Sepsis is one of the main causes of mortality in intensive care units (ICUs). Early prediction is critical for reducing injury. As approximately 36% of sepsis occur within 24 h after emergency department (ED) admission in Medical Information Mart for Intensive Care (MIMIC-IV), a prediction system for the ED triage stage would be helpful. Previous methods such as the quick Sequential Organ Failure Assessment (qSOFA) are more suitable for screening than for prediction in the ED, and we aimed to find a light-weight, convenient prediction method through machine learning.We accessed the MIMIC-IV for sepsis patient data in the EDs. Our dataset comprised demographic information, vital signs, and synthetic features. Extreme Gradient Boosting (XGBoost) was used to predict the risk of developing sepsis within 24 h after ED admission. Additionally, SHapley Additive exPlanations (SHAP) was employed to provide a comprehensive interpretation of the model's results. Ten percent of the patients were randomly selected as the testing set, while the remaining patients were used for training with 10-fold cross-validation.For 10-fold cross-validation on 14,957 samples, we reached an accuracy of 84.1%±0.3% and an area under the receiver operating characteristic (ROC) curve of 0.92±0.02. The model achieved similar performance on the testing set of 1,662 patients. SHAP values showed that the five most important features were acuity, arrival transportation, age, shock index, and respiratory rate.Machine learning models such as XGBoost may be used for sepsis prediction using only a small amount of data conveniently collected in the ED triage stage. This may help reduce workload in the ED and warn medical workers against the risk of sepsis in advance.Copyright: © World Journal of Emergency Medicine.

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%,  = 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,  = 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,  = 0.071). In conclusion, SPN in the acute phase had a positive impact on physical PICS for ventilated patients with COVID-19.Copyright © 2024 JCBN.

Acute skeletal muscle wasting in critical illness is associated with excess morbidity and mortality. Continuous feeding may suppress muscle protein synthesis as a result of the muscle-full effect, unlike intermittent feeding, which may ameliorate it.Does intermittent enteral feed decrease muscle wasting compared with continuous feed in critically ill patients?In a phase 2 interventional single-blinded randomized controlled trial, 121 mechanically ventilated adult patients with multiorgan failure were recruited following prospective informed consultee assent. They were randomized to the intervention group (intermittent enteral feeding from six 4-hourly feeds per 24 h, n = 62) or control group (standard continuous enteral feeding, n = 59). The primary outcome was 10-day loss of rectus femoris muscle cross-sectional area determined by ultrasound. Secondary outcomes included nutritional target achievements, plasma amino acid concentrations, glycemic control, and physical function milestones.Muscle loss was similar between arms (-1.1% [95% CI, -6.1% to -4.0%]; P =.676). More intermittently fed patients received 80% or more of target protein (OR, 1.52 [1.16-1.99]; P <.001) and energy (OR, 1.59 [1.21-2.08]; P =.001). Plasma branched-chain amino acid concentrations before and after feeds were similar between arms on trial day 1 (71 μM [44-98 μM]; P =.547) and trial day 10 (239 μM [33-444 μM]; P =.178). During the 10-day intervention period the coefficient of variation for glucose concentrations was higher with intermittent feed (17.84 [18.6-20.4]) vs continuous feed (12.98 [14.0-15.7]; P <.001). However, days with reported hypoglycemia and insulin usage were similar in both groups. Safety profiles, gastric intolerance, physical function milestones, and discharge destinations did not differ between groups.Intermittent feeding in early critical illness is not shown to preserve muscle mass in this trial despite resulting in a greater achievement of nutritional targets than continuous feeding. However, it is feasible and safe.ClinicalTrials.gov; No.: NCT02358512; URL: www.clinicaltrials.gov.Copyright © 2020 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

To explore the therapeutic effects of early enteral nutrition (EEN) on patients with sepsis on mechanical ventilation.Patients with sepsis on mechanical ventilation in the medical intensive care unit (ICU) from January 2013 to March 2016 were treated with enteral nutrition. Patients treated within 48 hours of initiation of mechanical ventilation were assigned to the EEN group, and the rest were assigned to the delayed enteral nutrition (DEN) group. Peripheral blood Th17 cells and Treg cells, endotoxin (ET) level, 28-day mortality, duration of mechanical ventilation, lengths of ICU stay and hospital stay, and incidence of ICU-acquired weakness (ICU-AW) were analyzed between the 2 groups.The proportion of Th17 cells and ET levels in the EEN group were significantly lower than those in the DEN group, whereas the proportion of Treg cells in the EEN group was remarkably higher than that in the DEN group (<.05). The duration of mechanical ventilation, lengths of ICU stay and hospital stay, and incidence of ICU-AW were higher in the DEN group than in the EEN group (<.05), but there was no significant difference in the 28-day mortality between the 2 groups.Patients with sepsis mainly present with an increased proportion of Th17 cells in the early stage, manifesting as enhanced immune response. Early enteral nutrition can inhibit the excessive immune response, shorten the duration of mechanical ventilation, lengths of ICU stay and hospital stay, and reduce the incidence of ICU-AW, but it has no obvious effect on 28-day mortality.

Previous studies demonstrate an accumulation of transferrin and transferrin receptor 1 (TfR1) in regenerating peripheral nerves. However, the expression and function of transferrin and TfR1 in the denervated skeletal muscle remain poorly understood. In this study, a mouse model of denervation was produced by complete tear of the left brachial plexus nerve. RNA-sequencing revealed that transferrin expression in the denervated skeletal muscle was upregulated, while TfR1 expression was downregulated. We also investigated the function of TfR1 during development and in adult skeletal muscles in mice with inducible deletion or loss of TfR1. The ablation of TfR1 in skeletal muscle in early development caused severe muscular atrophy and early death. In comparison, deletion of TfR1 in adult skeletal muscles did not affect survival or glucose metabolism, but caused skeletal muscle atrophy and motor functional impairment, similar to the muscular atrophy phenotype observed after denervation. These findings suggest that TfR1 plays an important role in muscle development and denervation-induced muscular atrophy. This study was approved by the Institutional Animal Care and Use Committee of Beijing Institute of Basic Medical Sciences, China (approval No. SYXK 2017-C023) on June 1, 2018.

There is clinical evidence that patients with heart failure and concomitant iron deficiency have increased skeletal muscle fatigability and impaired exercise tolerance. It was expected that a skeletal muscle cell line subjected to different degrees of iron availability and/or concomitant hypoxia would demonstrate changes in cell morphology and in the expression of atrophy markers. L6G8C5 rat skeletal myocytes were cultured in normoxia or hypoxia at optimal, reduced or increased iron concentrations. Experiments were performed to evaluate the iron content in cells, cell morphology, and the expression of muscle specific atrophy markers [Atrogin1 and muscle‑specific RING‑finger 1 (MuRF1)], a gene associated with the atrophy/hypertrophy balance [mothers against decapentaplegic homolog 4 (SMAD4)] and a muscle class‑III intermediate filament protein (Desmin) at the mRNA and protein level. Hypoxic treatment caused, as compared to normoxic conditions, an increase in the expression of Atrogin‑1 (P<0.001). Iron‑deficient cells exhibited morphological abnormalities and demonstrated a significant increase in the expression of Atrogin‑1 (P<0.05) and MuRF1 (P<0.05) both in normoxia and hypoxia, which indicated activation of the ubiquitin proteasome pathway associated with protein degradation during muscle atrophy. Depleted iron in cell culture combined with hypoxia also induced a decrease in SMAD4 expression (P<0.001) suggesting modifications leading to atrophy. In contrast, cells cultured in a medium enriched with iron during hypoxia exhibited inverse changes in the expression of atrophy markers (both P<0.05). Desmin was upregulated in cells subjected to both iron depletion and iron excess in normoxia and hypoxia (all P<0.05), but the greatest augmentation of mRNA expression occurred when iron depletion was combined with hypoxia. Notably, in hypoxia, an increased expression of Atrogin‑1 and MuRF1 was associated with an increased expression of transferrin receptor 1, reflecting intracellular iron demand (R=0.76, P<0.01; R=0.86, P<0.01). Hypoxia and iron deficiency when combined exhibited the most detrimental impact on skeletal myocytes, especially in the context of muscle atrophy markers. Conversely, iron supplementation in in vitro conditions acted in a protective manner on these cells.

Sarcopenia greatly reduces the quality of life of the elderly, and iron metabolism plays an important role in muscle loss. This study aimed to investigate the association between iron status and sarcopenia. A total of 286 adult patients hospitalized between 2019 and 2021 were included in this study, of which 117 were diagnosed with sarcopenia. Serum iron, total iron binding capacity (TIBC), transferrin, and transferrin saturation levels were compared between groups with and without sarcopenia and were included in the logistic analyses, with significant variables further included in the logistic regression model for the prediction of sarcopenia. Serum iron, TIBC, and transferrin levels decreased significantly in the sarcopenia group (p < 0.05), and were negatively associated with handgrip strength, relative skeletal muscle index, and multiple test performances (p < 0.05). Multivariate logistic analysis showed that sex, age, body mass index (BMI), and serum iron level were independent risk factors for sarcopenia. In the final logistic regression model, male sex (odds ratio [OR] 3.65, 95% confidence interval [CI] 1.67-7.98), age > 65 years (OR 5.40, 95% CI 2.25-12.95), BMI < 24 kg/m (OR 0.17, 95% CI 0.08-0.36), and serum iron < 10.95 μmol/L (OR 0.39, 95% CI 0.16-0.93) were included. Our study supported the impact of iron metabolism on muscle strength and performance.© 2024. The Author(s).

Serum tumor markers (STM), extensively used for the diagnosis, monitoring and prognostic assessment of tumors, can be increased in some non-malignant lung diseases. To date, there is a paucity of studies regarding the clinical characteristics of non-cystic fibrosis bronchiectasis patients with positive STMs.To investigate the clinical characteristics and indicators of bronchiectasis with positive STMs.The clinical data of 377 bronchiectasis patients was retrospectively collected from January 2017 to December 2019 from Beijing Chaoyang Hospital. Patients were divided into the STM negative group, the single STM positive group and the ≥2 STMs positive group according to the number of the positive STMs. The clinical characteristics are described and compared separately. The multivariate logistic regression analysis model was used to investigate the indicators regarding positive STMs.Patients in the ≥2 STMs positive group were older (P = 0.015), had higher mMRC scores (P < 0.001) and developed higher fever (P = 0.027). Additionally, these patients also had lower Albumin/Globulin Ratio (A/G), albumin (ALB), prealbumin (PAB) (P < 0.001, P < 0.001, P < 0.001, respectively) and higher CRP, ESR and Fbg (P < 0.001, P < 0.001 and P < 0.001, respectively). Age (OR 1.022, 95%CI 1.003-1.042; P = 0.026) and the number of affected lobes (OR 1.443, 95%CI 1.233-1.690; P < 0.001) were independently associated with one and ≥ 2 positive STMs in bronchiectasis patients.The ≥2 positive STMs are associated with a higher inflammation status and severer radiologic manifestations in bronchiectasis patients.© 2024. The Author(s).