Background: The investigation of mesenchymal stromal cell (MSC)-conditioned medium or extracellular vesicles (exosomes or microvesicles) as a remedy for acute lung injury (ALI) or acute respiratory distress syndrome (ARDS) has become a fast-growing field in recent years. Our purpose was to conduct a meta-analysis to investigate the efficacy of MSC-derived therapies (MDTs) for ALI/ARDS in animal models.Methods: A meta-analysis of MDTs for ALI/ARDS in animal trials was performed. PubMed and EMBASE were searched to screen relevant preclinical trials with a predetermined search strategy.Results: A total of 17 studies that compared MDT with the ALI control group were included in our study. The pooled result derived from the comparison of the two groups suggested that MDT could significantly reduce the lung injury score (standardized mean difference (SMD) = -4.02, 95% CI [- 5.28, -2.23], P < 0.0001) and improve animal survival (OR = -6.45, 95% CI [2.78, 14.97], P <0.0001). MDT mitigated the infiltration of neutrophils in alveoli (SMD = -3.38, 95% CI [-4.58, -2.18], P < 0.00001). MDT also reduced the wet-dry weight ratio of the lung (SMD = -2.34, 95% CI [-3.42, -1.26], P< 0.0001) and the total protein in BALF (SMD = -2.23, 95% CI [-3.07, -1.40], P < 0.00001). Furthermore, MDT was found to downregulate proinflammatory mediators such as IL-1, IL-6 and TNF-a and to upregulate anti-inflammatory mediators such as IL-10.Conclusion: MDT reduces lung injury and improves survival in animal ARDS models since it can ameliorate lung permeability, decrease inflammatory cell infiltration, downregulate proinflammatory mediators, and upregulate anti-inflammatory mediators. However, more animal studies and human trials are needed for further investigation.
Background: Although immunosuppression has been investigated in adult septic patients, early immune status remains unclear. In this study, we aimed to assess early immune status in adult patients with sepsis stratified by age and its relevance to hospital mortality. Methods: From post hoc analysis of a multicenter, randomized controlled trial, 273 patients whose levels of monocyte human leukocyte antigen-DR (mHLA-DR) were obtained within 48 hours after onset of sepsis were enrolled. All patients were divided into elderly (≥60yrs) group and non-elderly (<60yrs) group. Early immune status was evaluated by the percentage of mHLA-DR in total monocytes within 48 hours after onset of sepsis and it was classified as immunosuppression (mHLA-DR≤30%) or non-immunosuppression (>30%). Changes in immune status were assessed by the value change in mHLA-DR on day 3 compared with the first measurement. Three logistic regression models were conducted to test the associations between early immunosuppression and hospital mortality. We also did a sensitivity analysis to find out if the definition of early immune status (24 vs. 48 hours after onset of sepsis) affects the outcomes. Results: Of the 181 elderly and 92 non-elderly septic patients, 71 (39.2%) elderly and 25 (27.2%) non-elderly died in hospital. The percentage of early immunosuppression in the elderly was twice of that of the non-elderly patients (32% vs. 16%, p=0.006). Immunosuppressed elderly had higher hospital mortality than the non-immunosuppressed elderly (53.4% vs. 32.5%, p=0.009), but there was no significant difference in mortality between immunosuppresed non-elderly patients and non-immunosuppressed non-elderly patients (33.5% vs. 26.0%, p=0.541). In all of the three logistic regression models, we found that early immunosuppression was independently associated with increased hospital mortality in elderly, but not in non-elderly patients. Sensitivity analysis further confirmed the definition of early immune status did not affect the outcomes. In addition, immune status improvement on day 3 was associated with reduced hospital mortality in both elderly and non-elderly patients. Conclusion: In adult patients with sepsis, the elderly were more susceptible to early immunosuppression after onset of sepsis. Early immunosuppression was independently associated with poor prognosis in elderly patients. Trial registration: ClinicalTrials.gov NCT00711620 , 9 July 2008, https://clinicaltrials.gov/ct2/show/NCT00711620
Background Hand, foot, and mouth disease (HFMD) is an acute infectious disease caused by human enterovirus 71 (EV71), coxsackievirus, or echovirus, which are particularly common in preschool children. Severe HFMD is prone to cause pulmonary edema, and successively progresses to respiratory and circulatory failure; thus hemodynamic monitoring and fluid management are important in the treatment process. Methods We reviewed young patients with severe HFMD, caused by EV71, and who had been successfully treated in our department. A total of 20 patients met the inclusion criteria. Eight cases were monitored by the pulse indicator continuous cardiac output (PiCCO) technique, and fluid management was administered according to its parameters. With regard to the treatment with PiCCO monitoring, patients were divided into two groups: the PiCCO group (8 patients) and the control group (12 patients). The groups were then compared comprehensively to evaluate whether PiCCO monitoring could improve the clinical outcomes. Results After analysis, the findings were that although PiCCO failed to shorten the length of ICU stay, reduce the days of vasoactive drug usage, or reduce the number of cases which needed mechanical ventilation, it did reduce the incidence of fluid overload (p=0.085) and shortened the days of mechanical ventilation (p=0.028). After effective treatment, PiCCO monitoring showed that the cardiac index (CI) increased gradually(p<0.0001), whereas the pulse (P, p<0.0001), the extra vascular lung water index (EVLWI, p<0.0001), the global end diastolic volume index (GEDVI, p=0.0043), and the systemic vascular resistance index (SVRI, p<0.0001) all decreased gradually. Conclusion Our study discovered that PiCCO hemodynamic monitoring in young children with severe HFMD has potential clinical benefits, such as reducing fluid overload and duration of mechanical ventilation. However, whether it can ameliorate the severity of the disease, reduce mortality, or prevent multiple organ dysfunction remain to be further investigated.
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