Continuous veno-venous hemofiltration with oXiris hemofilters for the treatment of Fournier's gangrene: A case report series.

Background: Fournier's gangrene (FG) is a severe form of necrotizing fasciitis primarily caused by gram-negative bacteria. FG can rapidly progress to septic shock, resulting in high mortality rates. In the past, the management of the inflammatory response caused by gram-negative bacteria has been limited. Continuous Veno-Venous Hemofiltration with oXiris hemofilters (oXiris-CVVH) has shown promise in adsorbing inflammatory factors and endotoxins, making it an attractive approach for treating FG. This study aims to provide insights into the characteristics of patients with FG and septic shock who have been successfully treated using oXiris-CVVH, based on a series of patient cases. Results: This study presents the management of 4 cases in the intensive care units of a tertiary hospital in southern China. The use of oXiris-CVVH in patients with septic shock and FG yielded valuable practical insights. Conclusion: Based on the experience gained from these 4 cases, the utilization of oXiris-CVVH demonstrated potential in reducing the Sequential Organ Failure Assessment (SOFA) score, improving prognosis, and effectively lowering the levels of lactic acid and procalcitonin (PCT) in the blood. Additionally, it facilitated a reduction in the dosage of noradrenaline. Therefore, oXiris-CVVH should be considered as an adjunctive therapy in the treatment of patients with FG and septic shock.

CCL21 contributes to Th17 cell migration in neuroinflammation in obese mice following lead exposure.

Obesity and lead exposure can independently cause neuroinflammation, which is associated with neurodegenerative diseases. Although Th17 cells play critical roles in inflammatory diseases of the central nervous system, few studies have evaluated their role in neuroinflammation in the background of obesity and lead exposure. In this study, the mechanism underlying inflammatory injury was evaluated in a mouse model of high fat diet-induced obesity following lead exposure. Neuroinflammation was aggravated in mice with obesity following lead exposure, and this was accompanied by increases in Th17 cells in the brain and IL-17A and IL-22 secretion. An antibody array using Z310, a choroid plexus epithelium cell line, revealed that CCL21 was the most highly altered chemokine. CCL21 expression was higher in the choroid plexus of obese mice treated with lead than in mice with obesity or lead treatment alone and was higher in Z310 cells treated with lead and palmitic acid. CCL21 knockout reduced chemotaxis. Our findings suggest that lead exposure can aggravate inflammation in brain tissues of obese mice, possibly by the CCL21-mediated regulation of the passage of Th17 cells through the blood-cerebrospinal fluid barrier. Our findings provide new insights into the mechanism underlying the combined effects of lead and obesity.

Weaning critically ill patients from mechanical ventilation: a protocol from a multicenter retrospective cohort study.

BACKGROUND: Mechanical ventilation (MV) is an important lifesaving method in intensive care unit (ICU). Prolonged MV is associated with ventilator associated pneumonia (VAP) and other complications. However, premature weaning from MV may lead to higher risk of reintubation or mortality. Therefore, timely and safe weaning from MV is important. In addition, identification of the right patient and performing a suitable weaning process is necessary. Although several guidelines about weaning have been reported, compliance with these guidelines is unknown. Therefore, the aim of this study is to explore the variation of weaning in China, associations between initial MV reason and clinical outcomes, and factors associated with weaning strategies using a multicenter cohort. METHODS: This multicenter retrospective cohort study will be conducted at 17 adult ICUs in China, that included patients who were admitted in this 17 ICUs between October 2020 and February 2021. Patients under 18 years of age and patients without the possibility for weaning will be excluded. The questionnaire information will be registered by a specific clinician in each center who has been evaluated and qualified to carry out the study. DISCUSSION: In a previous observational study of weaning in 17 ICUs in China, weaning practices varies nationally. Therefore, a multicenter retrospective cohort study is necessary to be conducted to explore the present weaning methods used in China. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR) (No. ChiCTR2100044634).

Circulating microRNAs as novel diagnostic biomarkers and prognostic predictors for septic patients.

This study was to find out novel miRNAs whether could be used as diagnostic or prognostic biomarkers in sepsis. We used miRNAs microarray assays and further confirmed the levels of miRNAs in 151 septic patients' plasma. 56 miRNAs were up-regulated and 74 miRNAs down-regulated in septic patients compared with the healthy volunteers. But only miR-519c-5p and miR-3622b-3p were up-regulated in both septic and septic shock patients. The levels of miR-519c-5p and miR-3622b-3p were statistically higher in 151 septic patients than healthy controls on day 1. The AUC for miR-519c-5p was 0.79 (95% CI, 0.688-0.892, p = 0.001) in the diagnosis of sepsis, and the AUC for miR-3622b-3p 0.752 (95% CI, 0.622-0.881, p = 0.003). The AUC for the combination of these two miRNAs was 0.831 (95% CI, 0.74-0.923, p < 0.001). Besides, the AUC for miR-519c-5p was 0.597 (p = 0.043) in predicting 28-day mortality. MiR-519c-5p, miR-3622b-3p were novel biomarkers for diagnosing septic patients. High miR-519c-5p levels suggest a worse short-term prognosis. CLINICAL TRIAL REGISTRATION INFORMATION: Name of the registry: Diagnostic and prognostic value of circulating miRNA in patients with sepsis; Trial registration ID: ChiCTR-DDD-17013150; registered 30 October 2017; http://www.chictr.org.cn/edit.aspx?pid=22528&htm=4.

Cathepsin B aggravates acute pancreatitis by activating the NLRP3 inflammasome and promoting the caspase-1-induced pyroptosis.

OBJECTIVES: Cathepsin B (CTSB), nod-like receptor family pyrin domain-containing 3 (NLRP3), and caspase-1 play an important role in the development of Acute Pancreatitis (AP). Besides, the relationship between the proteins remains poorly understood. In addition, whereas previous studies have found caspase-1 activation in AP, pyroptosis, a caspase-1 induced cell death mode, has never been proposed and proved in AP. METHODS: We induced AP in mice by intraperitoneal injection of cerulein. Mice in the inhibitor group of CTSB were pretreated with injection of CA-074me, while mice in the inhibitor group of caspase-1 were of Ac-YVAD-CHO, 1 h earlier. We evaluated the inflammation of the pancreas and the detected expression of activated CTSB, NLRP3, ASC, caspase-1p20, IL-1ß and IL-18. TUNEL staining was used to detect acinar cell death. RESULTS: The inflammation of the pancreas in the two inhibitor groups was significantly reduced compared with that in the AP group. We observed that CA-074me not only inhibits CTSB, but also suppresses the expression and activity of NLRP3, ASC and caspase-1. We found that CA-074me further inhibits the downstream event of caspase-1, including pro-inflammatory cytokine secretion and pyroptosis. Whereas Ac-YVAD-CHO inhibited caspase-1 and decreased pro-inflammatory cytokine secretion and pyroptosis, it did not down-regulate the expression and activity ofCTSB, NLRP3 and ASC. CONCLUSION: The results indicate that CTSB may aggravate AP by activating the NLRP3 inflammasome and promoting Caspase-1-induced pyroptosis. These provide clues about the pathophysiological mechanisms of AP, shedding light on new ideas and potential targets for the prevention and treatment of AP.

The utility of MEWS for predicting the mortality in the elderly adults with COVID-19: a retrospective cohort study with comparison to other predictive clinical scores.

BACKGROUND: Older adults have been reported to be a population with high-risk of death in the COVID-19 outbreak. Rapid detection of high-risk patients is crucial to reduce mortality in this population. The aim of this study was to evaluate the prognositc accuracy of the Modified Early Warning Score (MEWS) for in-hospital mortality in older adults with COVID-19. METHODS: A retrospective cohort study was conducted in Wuhan Hankou Hospital in China from 1 January 2020 to 29 February 2020. Receiver operating characteristic (ROC) analysis was used to evaluate the predictive value of MEWS, Acute Physiology and Chronic Health Evaluation II (APACHE II), Sequential Organ Function Assessment (SOFA), quick Sequential Organ Function Assessment (qSOFA), Pneumonia Severity Index (PSI), Combination of Confusion, Urea, Respiratory Rate, Blood Pressure, and Age ≥65 (CURB-65), and the Systemic Inflammatory Response Syndrome Criteria (SIRS) for in-hospital mortality. Logistic regression models were performed to detect the high-risk older adults with COVID-19. RESULTS: Among the 235 patients included in this study, 37 (15.74%) died and 131 (55.74%) were male, with an average age of 70.61 years (SD 8.02). ROC analysis suggested that the capacity of MEWS in predicting in-hospital mortality was as good as the APACHE II, SOFA, PSI and qSOFA (Difference in AUROC: MEWS vs. APACHE II, -0.025 (95% CI [-0.075 to 0.026]); MEWS vs. SOFA, -0.013 (95% CI [-0.049 to 0.024]); MEWS vs. PSI, -0.015 (95% CI [-0.065 to 0.035]); MEWS vs. qSOFA, 0.024 (95% CI [-0.029 to 0.076]), all P > 0.05), but was significantly higher than SIRS and CURB-65 (Difference in AUROC: MEWS vs. SIRS, 0.218 (95% CI [0.156-0.279]); MEWS vs. CURB-65, 0.064 (95% CI [0.002-0.125]), all P < 0.05). Logistic regression models implied that the male patients (≥75 years) had higher risk of death than the other older adults (estimated coefficients: 1.16, P = 0.044). Our analysis further suggests that the cut-off points of the MEWS score for the male patients (≥75 years) subpopulation and the other elderly patients should be 2.5 and 3.5, respectively. CONCLUSIONS: MEWS is an efficient tool for rapid assessment of elderly COVID-19 patients. MEWS has promising performance in predicting in-hospital mortality and identifying the high-risk group in elderly patients with COVID-19.

MiRNA-133a aggravates inflammatory responses in sepsis by targeting SIRT1.

BACKGROUND: Sepsis is a systemic inflammatory response syndrome. MicroRNA (miRNA) plays an important role in immune cell activation, inflammatory cytokine release and immune response. However, the mechanism of miR-133a in sepsis remains largely unknown. METHODS: Sepsis mice models were established by applying the cecal ligation and puncture (CLP) method. Quantitative real-time polymerase chain reaction (qRT-PCR) assay was performed to detect the relative expression of miR-133a and inflammatory cytokines. Hematoxylin and eosin (H&E) staining and enzyme-linked immunosorbent assay (Elisa) were used to evaluate organ injury and inflammatory response. Besides, lipopolysaccharide (LPS)-induced RAW264.7 macrophages were used to construct sepsis cell models. Further, dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay were carried out to confirm the relationship between miR-133a and sirtuin-1 (SIRT1). In addition, western blot (WB) assay was performed to measure the relative SIRT1 protein level. RESULTS: MiR-133a was highly expressed in sepsis patients and CLP mice models. Knockdown of miR-133a inhibited sepsis-induced lung, liver and kidney injuries and inflammatory response in CLP mice models. Besides, miR-133a inhibitor also alleviated the inflammatory response of RAW264.7 macrophages induced by LPS. SIRT1 was a target of miR-133a, and silenced SIRT1 could reverse the anti-inflammatory effect of miR-133a inhibitor on LPS-induced sepsis cell models. CONCLUSION: MiR-133a promoted the inflammatory response of sepsis by inhibiting the expression of SIRT1, which might provide a new therapeutic strategy for sepsis.