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Background: Early enteral nutrition (EN) is recommended for patients with critical illness to maintain intestinal immunity. However, the optimal timing of the commencement of EN remains unclear, particularly after cardiovascular surgery., Objectives: We herein focused on Persistent Inflammation, Immunosuppression, and Catabolism Syndrome (PICS) as a predisposing immunodeficiency and investigated its association with very early EN (VEEN) (<24 h) in patients who underwent cardiovascular surgery., Methods: In this retrospective study, we used an administrative claims database with laboratory examinations between 2008 and 2021 to identify adult patients admitted to the intensive care unit after cardiovascular surgery. Patients who received EN the day after surgery were assigned to the EN <24 h group, whereas those who received EN on day 2 or day 3 were assigned to the control group. The primary outcome was a composite of the incidence of PICS and mortality on day 14 after surgery. We defined PICS as patients who were hospitalized for >14 day and meeting ≥2 of the following conditions: a lymphocyte count <800/μL, albumin <3.0 g/dL, and C-reactive protein >2.0 mg/dL. We compared the 2 groups using propensity score analysis., Results: A propensity score matching generated 2082 pairs. The primary outcome was significantly lower in the EN <24 h group than in the control group on days 14 {risk difference [95% confidence interval (CI)]: -3.1% [-5.9%, -0.3%]} and 28 (risk difference [95% CI]: -2.1% [-3.7%, -0.4%]). Mortality did not significantly differ between the 2 groups. The length of hospital stay was significantly shorter in the EN <24 h group: the difference (95% CI) was -2.2 (-3.7, -0.7) d., Conclusions: Among patients who underwent cardiovascular surgery, VEEN provided on the day after surgery was associated with a lower incidence of PICS and a shorter length of hospital stay than EN provided 2 day or 3 day after surgery., Competing Interests: Conflict of interest The authors report no conflicts of interest., (Copyright © 2024 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.)

Introduction: Persistent inflammation, immunosuppression, and catabolism syndrome (PICS) has been proposed as an endotype of chronic critical illness (CCI). The aim of this systematic review is to synthesise the available evidence of risk factors, biomarkers, and biological mechanisms underlying PICS., Methods: MEDLINE, CENTRAL, and EMBASE were searched on June 2, 2023. Our population of interest was adult intensive care unit survivors. The exposure group was patients with PICS and the comparator group was patients with no PICS, CCI, or rapid recovery. Mean differences were pooled for each biomarker using a random effects DerSimonian-Laird method. Risk of bias assessment was done using the Newcastle-Ottawa Scale., Results: Six papers were included. Five were single-centre retrospective cohort studies, and one was a prospective cohort study, with sample sizes ranging from 22 to 391 patients. Two studies showed an increased incidence of PICS with age, and two studies showed an association between PICS and Charlson Comorbidity Index scores. PICS was associated with requiring mechanical ventilation in four studies. Meta-analysis showed a 34.4 mg L -1 higher C-reactive protein (95% confidence interval [CI] 12.7-56.2 mg L -1 ; P<0.01), a 4.4 g L -1 lower albumin (95% CI 0.5-8.3 g L -1 ; P<0.01), and a 0.36×10 9 L -1 lower lymphocyte count (95% CI 0.25-0.47×10 9 L -1 ; P=0.01) in the PICS compared with the non-PICS group. There are a large variety of other potential biomarkers but limited validation studies. The overall quality of evidence is limited, and these results should be interpreted accordingly., Conclusions: While older patients and those with co-morbidities could be at greater risk for PICS, acquired risk factors, such as injury severity, are potentially more predictive of PICS than intrinsic patient characteristics. There are many potential biomarkers for PICS, but limited validation studies have been conducted. Persistent myeloid-derived suppressor cell expansion, the continual release of danger-associated molecular patterns and pathogen-associated molecular patterns propagating inflammation, and bioenergetic failure are all mechanisms underlying PICS that could offer potential for novel biomarkers and therapeutic interventions., Clinical Trial Registration: International Prospective Register of Systematic Reviews (PROSPERO; CRD42023427749)., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background & Aims: Early enteral nutrition (EEN) potentially improves immune-related outcomes via the maintenance of intestinal immunity; however, the effects of EEN on clinical outcomes, including infectious complications, are controversial. Therefore, we herein investigated whether EEN affected persistent inflammation, immunosuppression, and catabolism syndrome (PICS), which represents the immunocompromised state after critical illness., Methods: This retrospective cohort study utilized the administrative claims database of inpatients and laboratory findings. Patients admitted to and treated in the intensive care unit (ICU) for more than 3 consecutive days were included. The primary outcome, a composite of PICS or mortality on day 14 after admission, was compared between the EEN group, which received enteral nutrition (EN) on the first 3 days (day 0, 1, or 2), and the late enteral nutrition (LEN) group, which did not receive EN on the first 3 days, but then received EN on days 3 through 7, using a propensity score-matched analysis. Secondary outcomes included the composite outcome on day 28, in-hospital mortality, the Barthel index, and laboratory data. Patients who met at least two of the following conditions were diagnosed with PICS: CRP >2.0 mg/dL, albumin <3.0 g/dL, and a lymphocyte count <800/μL., Results: A total of 7530 matched pairs were generated after propensity score matching. The primary outcome was significantly lower in the EEN group (risk difference -3.0%, 95% confidence interval (CI) -4.5 to -1.4%), whereas mortality did not significantly differ. The 28-day composite outcome was similar in the 2 groups (risk difference -1.5%, 95% CI -2.8% to -0.2%, no significant difference in mortality). There was no significant difference in in-hospital mortality between the EEN and LEN groups; however, the Barthel index at discharge was higher in the EEN group (the medians, 50 vs 45, P = 0.001). Laboratory data showed lower Albumin and CRP on day 14 in the EEN group, but no other significant differences., Conclusions: In patients admitted to the ICU, EEN was associated with a lower incidence of PICS on days 14 and 28, but was not associated with mortality. This positive association was not observed in sepsis, cardiac diseases, or gastrointestinal diseases., Competing Interests: Conflict of interest None., (Copyright © 2024 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

This work aimed to explore whether the persistent inflammation induced by lipopolysaccharide (LPS) ameliorates fat accumulation by promoting adipose browning in vitro and in vivo. LPS over 1 ng/mL reduced lipid accumulation while increasing the expressions of specific genes involved in inflammation, mitochondrial biogenesis, and adipose browning in 3T3-L1 adipocytes. Moreover, LPS in intraperitoneal injection decreased white adipose tissue weight and elevated interscapular brown adipose tissue weight in mice. According to RT-PCR and western blot analysis results, the expressions of genes and proteins related to inflammation, mitochondrial biogenesis, lipolysis, and brown or beige markers in different tissues were elevated after LPS intervention. Cumulatively, LPS-induced persistent inflammation may potentially ameliorate fat accumulation by facilitating adipose browning in 3T3-L1 adipocytes and mice. These results offer new perspectives into the effect of persistent inflammation induced by LPS on regulating fat metabolism, thereby reducing fat accumulation by boosting adipose browning procedure., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2023. Published by Elsevier B.V.)

The prevention of fractures induced by inflammatory bone disease remains a clinical challenge. This is because of a lack of bone formation to fill in the bone defects, which are believed to be due in part to persistent inflammation caused by the imbalance of M1 over M2 macrophages. In this study, gold nanoparticles (AuNPs) were synthesized to shift the balance of macrophages at the site of bone damage to improve osteanagenesis in a mouse model of LPS-induced inflammatory bone erosion. Specifically, the AuNPs treatment improved bone structure and increased bone mineral density (BMD) by ~14% compared with model group. Macrophages recruited by LPS treatment were reduced by ~11% after AuNPs injection. Compared to LPS treatment only, the percentage of M2 macrophages increased threefold by AuNPs, while the proportion of M1 macrophages decreased by 59%. This promoted the regeneration of bone matrix proteins in the bone defect site, which finally leads to increased bone mass and improved bone structure in model mice. These data suggest that AuNPs could be a novel candidate therapeutic for inflammatory bone disease rather than a drug carrier., (Copyright © 2021 Elsevier Inc. All rights reserved.)