Could extracellular vesicles derived from mesenchymal stem cells be a potential therapy for acute pancreatitis-induced cardiac injury?

Acute pancreatitis(AP)often leads to a high incidence of cardiac injury,posing significant challenges in the treatment of severe AP and contributing to increased mortality rates.Mesenchymal stem cells(MSCs)release bioactive molecules that participate in various inflammatory diseases.Similarly,extracellular vesicles(EVs)secreted by MSCs have garnered extensive attention due to their comparable anti-inflammatory effects to MSCs and their potential to avoid risks associated with cell transplantation.Recently,the therapeutic potential of MSCs-EVs in various inflammatory diseases,including sepsis and AP,has gained increasing recognition.Although preclinical research on the utilization of MSCs-EVs in AP-induced cardiac injury is limited,several studies have demonstrated the positive effects of MSCs-EVs in regulating inflammation and immunity in sepsis-induced cardiac injury and cardiovascular diseases.Furthermore,clinical studies have been conducted on the therapeutic application of MSCs-EVs for some other diseases,wherein the contents of these EVs could be deliberately modified through prior modulation of MSCs.Consequently,we hypothesize that MSCs-EVs hold promise as a potential therapy for AP-induced cardiac injury.This paper aims to discuss this topic.However,additional research is essential to comprehensively elucidate the underlying mechanisms of MSCs-EVs in treating AP-induced cardiac injury,as well as to ascertain their safety and efficacy.

Role of penehyclidine in acute organophosphorus pesticide poisoning

BACKGROUND:Penehyclidine is a newly developed anticholinergic agent.We aimed to investigate the role of penehyclidine in acute organophosphorus pesticide poisoning(OP)patients.METHODS:We searched the Pubmed,Cochrane library,EMBASE,Chinese National Knowledge Infrastructure(CNKI),Chinese Biomedical literature(CBM)and Wanfang databases.Randomized controlled trials(RCTs)recruiting acute OP patients were identifi ed for meta-analysis.Main outcomes included cure rate,mortality rate,time to atropinization,time to 60%normal acetylcholinesterase(AchE)level,rate of intermediate syndrome(IMS)and rate of adverse drug reactions(ADR).RESULTS:Sixteen RCTs involving 1,334 patients were identifi ed.Compared with the atropineor penehyclidine-alone groups,atropine combined with penehyclidine significantly increased the cure rate(penehyclidine+atropine vs.atropine,0.97 vs.0.86,RR 1.13,95%CI[1.07–1.19];penehyclidine+atropine vs.penehyclidine,0.93 vs.0.80,RR 1.08,95%CI[1.01–1.15])and reduced the mortality rate(penehyclidine+atropine vs.atropine,0.015 vs.0.11,RR 0.17,95%CI[0.06–0.49];penehyclidine+atropine vs.penehyclidine,0.13 vs.0.08,RR 0.23,95%CI[0.04–1.28]).Atropine combined with penehyclidine in OP patients also helped reduce the time to atropinization and AchE recovery,the rate of IMS and the rate of ADR.Compared with a single dose of atropine,a single dose of penehyclidine also signifi cantly elevated the cure rate,reduced times to atropinization,AchE recovery,and rate of IMS.CONCLUSION:Atropine combined with penehyclidine benefi ts OP patients by enhancing the cure rate,mortality rate,time to atropinization,AchE recovery,IMS rate,total ADR and duration of hospitalization.Penehyclidine combined with atropine is likely a better initial therapy for OP patients than atropine alone.

Efficacy and safety of corticosteroids in immunocompetent patients with septic shock

BACKGROUND: The use of corticosteroids in septic shock has been studied for many decades but yielded conflicting results. We conducted a systematic review to evaluate the efficacy and the safety of corticosteroids in immunocompetent patients with septic shock.METHODS: Medline via Pub Med, Cochrane Central Register of Controlled Trials(CENTRAL) in the Cochrane Library, and EMBASE were searched from inception to March 2020. Two reviewers independently identified randomized controlled trials(RCTs) comparing corticosteroids with a control group for immunocompetent patients with septic shock. Data were abstracted and reported following the Cochrane Handbook for Systematic Review of Intervention and Preferred Reporting Items for Systematic Reviews and Meta-Analyses(PRISMA) statement. The efficacy outcome included mortality and shock reversal. The safety outcomes were infection, gastrointestinal bleeding, and hyperglycemia.RESULTS: Nine RCTs with a total of 1,298 patients were included. Compared with the control group, corticosteroid group did not lower the short-term(28 or 30 days) mortality(risk ratio [RR] 0.95, 95% confidence interval(CI) 0.85 to 1.06, inconsistency [I2]=0%, trial sequential analysis [TSA]-adjusted CI 0.83 to 1.09, moderate-certainty evidence). Corticosteroids significantly shortened the time to shock reversal compared with the control group(mean difference [MD] –21.56 hours;95% CI –32.95 to –10.16, I2=0%;TSA-adjusted CI –33.33 to –9.78, moderate-certainty evidence). The corticosteroid treatment was associated with an increased risk of hyperglycemia but not the infection or gastrointestinal bleeding.CONCLUSIONS: The corticosteroid treatment is not associated with lower short-or longterm mortality compared with placebo in immunocompetent patients with septic shock. However, corticosteroids significantly shorten the time to shock reversal without increasing the risk of infection. The patient's immune status should also be considered during clinical treatment and clinical trials in future.

Is rosuvastatin protective against sepsis-associated encephalopathy? A secondary analysis of the SAILS trial

BACKGROUND:Sepsis is a common cause of death in emergency departments and sepsis-associated encephalopathy(SAE)is a major complication.Rosuvastatin may play a neuroprotective role due to its protective effects on the vascular endothelium and its anti-inflammatory functions.Our study aimed to explore the potential protective function of rosuvastatin against SAE.METHODS:Sepsis patients without any neurological dysfunction on admission were prospectively enrolled in the“Rosuvastatin for Sepsis-Associated Acute Respiratory Distress Syndrome”study(SAILS trial,ClinicalTrials.gov number:NCT00979121).Patients were divided into rosuvastatin and placebo groups.This is a secondary analysis of the SAILS dataset.Baseline characteristics,therapy outcomes,and adverse drug events were compared between groups.RESULTS:A total of 86 patients were eligible for our study.Of these patients,51 were treated with rosuvastatin.There were significantly fewer cases of SAE in the rosuvastatin group than in the placebo group(32.1%vs.57.1%,P=0.028).However,creatine kinase levels were significantly higher in the rosuvastatin group than in the placebo group(233[22-689]U/L vs.79[12-206]U/L,P=0.034).CONCLUSION:Rosuvastatin appears to have a protective role against SAE but may result in a higher incidence of adverse events.

β-receptor blocker influences return of spontaneous circulation and chemical examination in rats during cardiopulmonary resuscitation

Objective:We investigated the influence of β-receptor blocker metoprolol on return of spontaneous circulation(ROSC) during cardiopulmonary resuscitation(CPR) in rats with induced myocardial infarction(MI).Methods:Male Sprague-Dawley rats were randomly divided into three groups:the sham-operated group,the MI group without metoprolol,which was fed the vehicle,and the MI+metoprolol group receiving intragastric metoprolol.Each group was further divided randomly into three subgroups,depending on the dosage of epinephrine administered during subsequent CPR applied after the induction of asphyxial cardiac arrest.Results:The ROSC rate was significantly decreased in the low dose subgroup of MI group,unchanged in the medium dose subgroup of MI group,and significantly decreased in the high dose subgroup of MI group,compared with the same dose subgroup of sham-operated group.MI+metoprolol group had a lower ROSC rate than MI group in the medium dose subgroup,and a higher ROSC rate than MI group in the high dose subgroup.There was no difference in blood K+ values of successful rats between MI group and MI+metoprolol group.The rats with successful CPR had lower blood K+ values than rats with unsuccessful CPR in each of the three treatment groups.Conclusions:Metoprolol administered to MI rats over a long period significantly improved ROSC rates under an appropriate dose of epinephrine during CPR.An increasing high blood K+ value would attenuate the rate of a successful CPR.