| ObjectiveAcute upper gastrointestinal bleeding(AUGIB)is one of the most common acute and critical illnesses worldwide,with a high mortality rate,and most of the dead patients have past comorbidities.Acute dangerous upper gastrointestinal bleeding refers to bleeding that causes hemodynamic disorders and organ dysfunction within less than 24 hours due to excessive bleeding(bleeding volume>1000ml or more than 20%of circulating blood volume).Acute dangerous upper gastrointestinal bleeding is one of the common causes of emergency treatment,characterized by acute onset,large bleeding volume,and high mortality rate.It is a key focus that emergency physicians need to pay attention to.The first part of this study focuses on patients with acute dangerous upper gastrointestinal bleeding as the research object,collects relevant epidemiological,treatment,prognosis and other data,identifies the high-risk population for acute dangerous upper gastrointestinal bleeding,and analyzes the risk factors for death in patients with acute dangerous upper gastrointestinal bleeding.The second part of this study mainly investigates the changes in intestinal microbiota in patients with acute dangerous upper gastrointestinal bleeding using macrogene sequencing technology,providing a basis for further exploration of the role of intestinal microbiota in the treatment of patients with acute dangerous upper gastrointestinal bleeding.The third part of this study compared the clinical outcomes of acute dangerous upper gastrointestinal bleeding patients with or without prophylactic antibiotic,to determine the population stratification that requires prophylactic antibiotic.MethodIn the first part of this study,we collected patients with acute dangerous upper gastrointestinal bleeding who were admitted to the emergency department of Peking Union Medical College Hospital,Chinese Academy of Medical Sciences from January 1,2019 to December 31,2021.Collect patients’ past history,medication history,onset status,etiology,treatment interventions,outcomes,and causes of death,and identify high-risk factors related to death.In the second part of this study,a prospective study was conducted,selecting three groups of study subjects:healthy adults,patients with non-variceal gastrointestinal bleeding,and patients with cirrhotic variceal bleeding.Fecal samples were collected,and their intestinal microbiota was studied using metagenomic method,to analyze changes in the patient’s intestinal microbiota.The third part of this study collect patients with acute dangerous upper gastrointestinal bleeding admitted between 1 January 2019 and 31 December 2021 in the Emergency Department Rescue Room of Peking Union Medical College Hospital,Chinese Academy of Medical Sciences.Patients were divided into prophylactic antibiotics and non-prophylactic antibiotics groups.The primary outcome was in-hospital mortality,and the secondary outcome was new infection.The patients were also divided into two groups considering whether they developed infections in-hospital.The risk factors for infection were analyzed,and population stratification for prophylactic antibiotics was determined.collected the patients with acute dangerous upper gastrointestinal bleeding who were admitted to the emergency department of Peking Union Medical College Hospital,Chinese Academy of Medical Sciences from January 1,2019 to December 31,2021.The patients were divided into antibiotic exposure group and nonexposure group,with the main outcome indicator being hospital death and the secondary outcome indicator being new infections in the hospital.Then divide the patients into two groups based on whether they are infected,analyze the risk factors for infection,and discuss the population stratification for preventive antibiotic use.ResultThe first part of the study showed that the most common cause of acute dangerous upper gastrointestinal bleeding is variceal bleeding(38.42%).The risk factors of death for patients with variceal bleeding are advanced age(P=0.001),use of anticoagulants(P=0.030),higher particle to lymphocyte ratio(P=0.001),lower platelets(P=0.024),higher Cr(P=0.000)and BUN(P=0.000),higher Nt-ProBNP(P=0.003),lower pH(P=0.024),higher Lac(P=0.020),higher PT(P=0.000),INR(P=0.000),APTT(P=0.000),and lower Fbg(P=0.043),and tracheal intubation(P=0.000),plasma infusion(P=0.014),and platelet therapy(P=0.000)were performed,and followed by myocardial injury(P=0.000)and hospital infection(P=0.045)after bleeding.The independent risk factor is advanced age(OR:1.128,95%CI:1.033-1.231,P=0.007).The risk factors of death for non-variceal bleeding patients are advanced age(P=0.014),male(P=0.045),GCS<15(P=0.003),fever(P=0.014),lower hemoglobin(P=0.023)and hematocrit(P=0.026).lower albumin(P=0.047),higher BUN(P=0.034),lower partial pressure of carbon dioxide(P=0.035),higher lactate(P=0.009),and longer APTT(P=0.030),and tracheal intubation(P=0.000),no endoscopy(P=0.001),plasma infusion(P=0.001),and platelet therapy(P=0.000),and myocardial injury after bleeding(P=0.000).The independent risk factors were advanced age(OR:1.067,95%CI:1.006-1.131,P=0.031),male(OR:0.085,95%CI:0.011-0.649,P=0.017),and no endoscopic examination(OR:8.569,95%CI:2.09735.014,P=0.003).The second part of the study showed that there was a significant difference in the abundance of intestinal microbiota at the phylum level between patients with varicose and non-varicose acute dangerous upper gastrointestinal bleeding and healthy adults(P<0.05).Compared with healthy adults,the abundance of Actinobacteria communities in patients with acute upper gastrointestinal bleeding significantly decreased(P<0.01).while the abundance of Bacteroides and Proteobacteria communities significantly increased(P<0.01);Compared to non-variceal bleeding patients and healthy adults,the abundance of the Verrucomicrobia in patients with variceal bleeding significantly decreased(P<0.01),while the abundance of the Campylobacter genus community significantly increased(P<0.05).Compared to the healthy adult group,the pathogenicity and mobile elements of the intestinal microbiota in patients with acute dangerous upper gastrointestinal bleeding were upregulated(P<0.05),while biofilm formation was downregulated(P<0.05),indicating that the above phenotypes of intestinal microbiota in patients with acute dangerous upper gastrointestinal bleeding were abnormal;Compared to non-variceal bleeding patients,the pathogenicity and anaerobic status of intestinal microbiota in patients with variceal bleeding were upregulated(P<0.05),while the mobile element was downregulated(P<0.05),indicating that the above phenotypes of intestinal microbiota in patients with variceal bleeding was abnormal.The third part of the study showed that the mortality rates were significantly lower in patients with versus without prophylactic antibiotics(6.41%versus 17.12%,respectively;P=0.001).The risk factors for infection were varicose veins(P=0.045)and endotracheal intubation(P=0.005)in patients with prophylactic antibiotics,and endoscopic treatment(P=0.010)in patients without prophylactic antibiotics.Stratified analyses showed that patients aged≥65 years,with endotracheal intubation,endoscopic treatment,and acute dangerous upper gastrointestinal bleeding of variceal etiologies benefited from prophylactic antibiotics.ConclusionThe most common cause of acute dangerous upper gastrointestinal bleeding in emergency patients is variceal bleeding.The risk factors for death in patients with variceal bleeding is advanced age;the risk factors for death in patients with non-variceal bleeding are advanced age,male,and no endoscopic examination.In patients with acute dangerous upper gastrointestinal bleeding,the dominant species of intestinal microbiota have changed,and the concentration of beneficial bacteria has decreased.Varicose bleeding may be related to a decrease in the concentration of Verrucomicrobia,and an increase in the concentration of harmful bacteria.The main pathogenic bacteria may be Bacteroidetes and Proteobacteria.The pathogenicity of intestinal microbiota in patients with acute upper gastrointestinal bleeding is enhanced,and regulating intestinal microbiota may have certain benefits for treatment.The current study suggested that patients with acute dangerous upper gastrointestinal bleeding benefited from prophylactic antibiotics to decrease mortality,especially those aged≥65 years and those with endotracheal intubation,endoscopic treatment,and variceal etiologies. |