Advances of mesenchymal stem cells and their derived extracellular vesicles as a promising therapy for acute respiratory distress syndrome: from bench to clinic.

Acute respiratory distress syndrome (ARDS) is an acute inflammatory lung injury characterized by diffuse alveolar damage. The period prevalence of ARDS was 10.4% of ICU admissions in 50 countries. Although great progress has been made in supportive care, the hospital mortality rate of severe ARDS is still up to 46.1%. Moreover, up to now, there is no effective pharmacotherapy for ARDS and most clinical trials focusing on consistently effective drugs have met disappointing results. Mesenchymal stem cells (MSCs) and their derived extracellular vesicles (EVs) have spawned intense interest of a wide range of researchers and clinicians due to their robust anti-inflammatory, anti-apoptotic and tissue regeneration properties. A growing body of evidence from preclinical studies confirmed the promising therapeutic potential of MSCs and their EVs in the treatment of ARDS. Based on the inspiring experimental results, clinical trials have been designed to evaluate safety and efficacy of MSCs and their EVs in ARDS patients. Moreover, trials exploring their optimal time window and regimen of drug administration are ongoing. Therefore, this review aims to present an overview of the characteristics of mesenchymal stem cells and their derived EVs, therapeutic mechanisms for ARDS and research progress that has been made over the past 5 years.

Impact of SARS-CoV-2 vaccination in inflammatory bowel disease patients with different biological agents: a systematic review and meta-analysis.

BACKGROUND: There are concerns regarding the effect of biological agents on SARS-CoV-2 vaccination in patients with inflammatory bowel disease (IBD). A systematic review and meta-analysis was performed about the serological responses, breakthrough infections and clinical relapse of IBD patients treated with biological agents following SARS-CoV-2 vaccination. METHODS: Electronic databases were searched to identify relevant studies. Primary outcomes were the pooled seroconversion rates, breakthrough infection rates and clinical relapse rates after SARS-CoV-2 vaccination in IBD patients treated with biological agents. Secondary outcomes were the comparison of seroconversion rates, breakthrough infection rates and clinical relapse rates in IBD patients treated with biological agents and control cohort after SARS-CoV-2 vaccination. RESULTS: Thirty-five studies were included in this meta-analysis. A high percentage of seroconversion (96.6%, 99% and 99.2%) was achieved in IBD patients treated with anti-TNF-α therapy, vedolizumab and ustekinumab after SARS-CoV-2 vaccination, respectively. The pooled breakthrough infection rate was 2.5% and 3.9% in IBD patients treated with anti-TNF-α therapy and vedolizumab, respectively. The breakthrough infection rate in IBD patients treated with anti-TNF-α therapy was significantly lower than control cohort (RR 0.178, 95% CI 0.084-0.378). The pooled clinical relapse rate in IBD patients treated with anti-TNF-α therapy, vedolizumab and ustekinumab was 6.9%, 5.4% and 5.3%, respectively. CONCLUSION: The overall seroconversion rate after SARS-CoV-2 vaccination in IBD patients treated with biological agents is high. The overall breakthrough infection rate and clinical relapse rate in IBD patients treated with biological agents were low.

The diagnostic and predictive value of fecal calprotectin and capsule endoscopy for small-bowel Crohn's disease: a systematic review and meta-analysis.

BACKGROUND: there are no clarified non-invasive methods to evaluate small bowel inflammation in Crohn's disease. AIMS: to evaluate the accuracy of fecal calprotectin and capsule endoscopy for the diagnosis of small bowel Crohn's disease and to predict relapse. METHODS: a systematic literature search was performed for studies to diagnose and predict relapse of the disease with fecal calprotectin and capsule endoscopy. The relevant pooled data including sensitivity, specificity, diagnostic odds ratio, positive likelihood ratio, negative likelihood ratio and area under curve were calculated using Stata 14.0. RESULTS: twenty-one studies were included in the final analyses. The diagnostic accuracy of the disease and relapse were obtained for capsule endoscopy, with a pooled sensitivity of 0.90 and 0.82, specificity of 0.76 and 0.56, diagnostic odds ratio of 33 and 6, and area under curve of 0.92 and 0.82, respectively. Diagnostic accuracy of the disease was calculated for fecal calprotectin values of 50, 100 and 200 ug/g; the sensitivity values were 0.84, 0.66 and 0.45; specificity values were 0.49, 0.74 and 0.87; diagnostic odds ratio were 5, 5 and 5; and area under curve were 0.74, 0.76 and 0.75, respectively. A fecal calprotectin level of 100-140 ug/g for the prediction of relapse had a pooled sensitivity of 0.68, specificity of 0.91, diagnostic odds ratio of 21, and area under curve of 0.77. CONCLUSION: capsule endoscopy is effective in diagnosing small bowel Crohn's disease and predicting relapse. Fecal calprotectin is an accurate surrogate technique to diagnose small bowel inflammation in Crohn's disease. Furthermore, the best scenario for fecal calprotectin is the prediction of relapse.