BACKGROUND Acute cholangitis is caused by bacterial infection and has high morbidity and mortality risk.The grade of cholangitis can guide clinical treatment from single antibiotic treatment to biliary drainage.With t...BACKGROUND Acute cholangitis is caused by bacterial infection and has high morbidity and mortality risk.The grade of cholangitis can guide clinical treatment from single antibiotic treatment to biliary drainage.With the introduction of white blood cell(WBC)count,C-reactive protein(CRP),and total bilirubin(T-Bil)into the diagnostic criteria and severity grading for acute cholangitis,the diagnosis rate and grading have significantly improved.However,early risk stratification assessments are challenging in the emergency department.Therefore,we hope to find an ideal predictive biomarker for cholangitis grade.Presepsin is a promising biomarker for the early diagnosis,severity,and prognosis of acute bacterial infections.AIM To assess the grading value of presepsin in patients with acute cholangitis.METHODS This clinical study was conducted at the Beijing Friendship Hospital,a 2000-bed teaching hospital with approximately 200000 emergency admissions per year.In this prospective observational study,336 patients with acute cholangitis meeting the Tokyo Guidelines 2018 diagnostic criteria in the emergency department from May 2019 to December 2020 were analyzed.WBC count,CRP,procalcitonin(PCT),presepsin,T-Bil,and blood culture results were collected.The values were compared using the Pearsonχ2 test,Fisher’s exact test,or Mann-Whitney U test.The area under the receiver operating characteristic curve(AUC)of the value was examined using the Delong test.The correlations among the key research indicators were determined using Pearson correlation.RESULTS In total,336 patients were examined,which included 107,106,and 123 patients classified as having mild,moderate,and severe cholangitis,respectively.WBC count,CRP,PCT,presepsin,T-Bil,direct bilirubin,and sequential organ failure assessment scores of moderate and severe cholangitis patients were higher than those of mild cholangitis patients(P=0.000).The AUC of presepsin in predicting moderate acute cholangitis was 0.728,which was higher than that of CRP(0.631,P=0.043)and PCT(0.585,P=0.002),and same as that of WBC count(0.746,P=0.713)and T-Bil(0.686,P=0.361).The AUC of presepsin in predicting severe acute cholangitis was 0.715,which was higher than that of WBC count(0.571,P=0.008),CRP(0.590,P=0.009),PCT(0.618,P=0.024),and T-Bil(0.559,P=0.006).The presepsin levels in the positive blood culture group were higher(2830.8pg/mLvs1987.8pg/mL,P=0.000),and the AUC of presepsin(0.688)proved that it was a good biomarker for predicting positive bacterial culture.CONCLUSION Presepsin can predict positive blood culture in patients with acute cholangitis.It is superior to WBC count,CRP,PCT,and T-Bil for the risk stratification of acute cholangitis.展开更多
Dear editor,Herpes B virus(BV),also known as Macacine herpesvirus 1(family:Herpesviridae,subfamily:Alphaherpesvirinae,genus:Simplexvirus),officially designated by the International Committee on the Taxonomy of Viruses...Dear editor,Herpes B virus(BV),also known as Macacine herpesvirus 1(family:Herpesviridae,subfamily:Alphaherpesvirinae,genus:Simplexvirus),officially designated by the International Committee on the Taxonomy of Viruses,exhibits serologic cross-reactivity with other members of the genus Simplexvirus,namely HSV type 1(HSV-1),the causative agent of oral herpetic ulcers(cold sores)in humans and HSV type 2(HSV-2),the agent of human genital herpes.[1]展开更多
BACKGROUND Acute pancreatitis(AP) is an inflammatory disorder of the pancreas with an unpredictable course of illness. A major challenge of AP is the early identification of patients at high-risk for organ failure and...BACKGROUND Acute pancreatitis(AP) is an inflammatory disorder of the pancreas with an unpredictable course of illness. A major challenge of AP is the early identification of patients at high-risk for organ failure and death. However, scoring systems are complicated and time consuming, and the predictive values for the clinical course are vague.AIM To determine whether the dynamic changes in presepsin levels can be used to evaluate the severity of disease and outcome of AP.METHODS In this multicentric cohort study, 133 patients with AP were included. Clinical severity was dynamically evaluated using the 2012 revised Atlanta Classification. Blood presepsin levels were measured at days 1, 3, 5 and 7 after admission by chemiluminescent enzyme immunoassay.RESULTS The median concentration of presepsin increased and the clearance rate of presepsin decreased with disease severity and organ failure in AP patients. The presepsin levels on days 3, 5 and 7 were independent predictors of moderately severe and severe AP with time-specific area under the curve(AUC) values of 0.827, 0.848 and 0.867, respectively. The presepsin levels positively correlated with bedside index of severity in AP, Ranson, acute physiology and chronic health evaluation II, computed tomography severity index and Marshall scores. Presepsin levels on days 3, 5 and 7 were independent predictors of 28-d mortality of AP patients with AUC values of 0.781, 0.846 and 0.843, respectively.CONCLUSION Blood presepsin levels within 7 d of admission were associated with and may be useful to dynamically predict the severity of disease course and 28-d mortality in AP patients.展开更多
BACKGROUND:This study aimed to explore the changes of programmed death-ligand 1(PDL1)and programmed death-1(PD-1)expression on antigen-presenting cells(APCs)and evaluate their association with organ failure and mortal...BACKGROUND:This study aimed to explore the changes of programmed death-ligand 1(PDL1)and programmed death-1(PD-1)expression on antigen-presenting cells(APCs)and evaluate their association with organ failure and mortality during early sepsis.METHODS:In total,40 healthy controls and 198 patients with sepsis were included in this study.Peripheral blood was collected within the first 24 h after the diagnosis of sepsis.The expression of PDL1 and PD-1 was determined on APCs,such as B cells,monocytes,and dendritic cells(DCs),by flow cytometry.Cytokines in plasma,such as interferon-γ(IFN-γ),tumor necrosis factor-α(TNF-α),interleukin-4(IL-4),IL-6,IL-10,and IL-17A were determined by Luminex assay.RESULTS:PD-1 expression decreased significantly on B cells,monocytes,myeloid DCs(mDCs),and plasmacytoid DCs(pDCs)as the severity of sepsis increased.PD-1 expression was also markedly decreased in non-survivors compared with survivors.In contrast,PD-L1 expression was markedly higher on mDCs,pDCs,and monocytes in patients with sepsis than in healthy controls and in non-survivors than in survivors.The PD-L1 expression on APCs(monocytes and DCs)was weakly related to organ dysfunction and infl ammation.The area under the receiver operating characteristic curve(AUC)of the PD-1 percentage of monocytes(monocyte PD-1%)+APACHE II model(0.823)and monocyte PD-1%+SOFA model(0.816)had higher prognostic value than other parameters alone.Monocyte PD-1%was an independent risk factor for 28-day mortality.CONCLUSION:The severity of sepsis was correlated with PD-L1 or PD-1 over-expression on APCs.PD-L1 in monocytes and DCs was weakly correlated with infl ammation and organ dysfunction during early sepsis.The combination of SOFA or APACHE II scores with monocyte PD-1%could improve the prediction ability for mortality.展开更多
BACKGROUND Bacteremia,which is a major cause of mortality in patients with acute cholangitis,induces hyperactive immune response and mitochondrial dysfunction.Presepsin is responsible for pathogen recognition by innat...BACKGROUND Bacteremia,which is a major cause of mortality in patients with acute cholangitis,induces hyperactive immune response and mitochondrial dysfunction.Presepsin is responsible for pathogen recognition by innate immunity.Acylcarnitines are established mitochondrial biomarkers.AIM To clarify the early predictive value of presepsin and acylcarnitines as biomarkers of severity of acute cholangitis and the need for biliary drainage.METHODS Of 280 patients with acute cholangitis were included and the severity was stratified according to the Tokyo Guidelines 2018.Blood presepsin and plasma acylcarnitines were tested at enrollment by chemiluminescent enzyme immunoassay and ultra-high-performance liquid chromatography-mass spectrometry,respectively.RESULTS The concentrations of presepsin,procalcitonin,short-and medium-chain acylcarnitines increased,while long-chain acylcarnitines decreased with the severity of acute cholangitis.The areas under the receiver operating characteristic curves(AUC)of presepsin for diagnosing moderate/severe and severe cholangitis(0.823 and 0.801,respectively)were greater than those of conventional markers.The combination of presepsin,direct bilirubin,alanine aminotransferase,temperature,and butyryl-L-carnitine showed good predictive ability for biliary drainage(AUC:0.723).Presepsin,procalcitonin,acetyl-L-carnitine,hydroxydodecenoyl-Lcarnitine,and temperature were independent predictors of bloodstream infection.After adjusting for severity classification,acetyl-L-carnitine was the only acylcarnitine independently associated with 28-d mortality(hazard ratio 14.396;P<0.001)(AUC:0.880).Presepsin concentration showed positive correlation with direct bilirubin or acetyl-L-carnitine.CONCLUSION Presepsin could serve as a specific biomarker to predict the severity of acute cholangitis and need for biliary drainage.Acetyl-L-carnitine is a potential prognostic factor for patients with acute cholangitis.Innate immune response was associated with mitochondrial metabolic dysfunction in acute cholangitis.展开更多
BACKGROUND:Acute pulmonary embolism(APE)with cardiac arrest(CA)is characterized by high mortality in emergency due to pulmonary arterial hypertension(PAH).This study aims to determine whether early pulmonary artery re...BACKGROUND:Acute pulmonary embolism(APE)with cardiac arrest(CA)is characterized by high mortality in emergency due to pulmonary arterial hypertension(PAH).This study aims to determine whether early pulmonary artery remodeling occurs in PAH caused by massive APE with CA and the protective effects of increasing angiotensin-converting enzyme(ACE)2-angiotensin(Ang)(1-7)-Mas receptor axis and ACE-Ang II-Ang II type 1 receptor(AT1)axis(ACE2/ACE axes)ratio on pulmonary artery lesion after return of spontaneous circulation(ROSC).METHODS:To establish a porcine massive APE with CA model,autologous thrombus was injected into the external jugular vein until mean arterial pressure dropped below 30 mmHg(1 mmHg=0.133 kPa).Cardiopulmonary resuscitation and thrombolysis were delivered to regain spontaneous circulation.Pigs were divided into four groups of five pigs each:control group,APE-CA group,ROSC-saline group,and ROSC-captopril group,to examine the endothelial pathological changes and expression of ACE2/ACE axes in pulmonary artery with or without captopril.RESULTS:Histological analysis of samples from the APE-CA and ROSC-saline groups showed that pulmonary arterioles were almost completely occluded by accumulated endothelial cells.Western blotting analysis revealed a decrease in the pulmonary arterial ACE2/ACE axes ratio and increases in angiopoietin-2/angiopoietin-1 ratio and expression of vascular endothelial growth factor(VEGF)in the APE-CA group compared with the control group.Captopril significantly suppressed the activation of angiopoietin-2/angiopoietin-1 and VEGF in plexiform lesions formed by proliferative endothelial cells after ROSC.Captopril also alleviated endothelial cell apoptosis by increasing the B-cell lymphoma-2(Bcl-2)/Bcl-2-associated X(Bax)ratio and decreasing cleaved caspase-3 expression.CONCLUSION:Increasing the ACE2/ACE axes ratio may ameliorate pulmonary arterial remodeling by inhibiting the apoptosis and proliferation of endothelial cells after ROSC induced by APE.展开更多
1.Introduction Sudden cardiac death(SCD)refers to sudden death due to a variety of cardiac causes.It is manifested as a sudden loss of consciousness,cardiac arrest,and respiratory arrest and generally shows early symp...1.Introduction Sudden cardiac death(SCD)refers to sudden death due to a variety of cardiac causes.It is manifested as a sudden loss of consciousness,cardiac arrest,and respiratory arrest and generally shows early symptoms that are atypical and not easily detected[1].According to a recent study,nearly 544000 patients suffer from SCD every year in China[2].展开更多
基金by National Natural Science Foundation of China,No.81773931Beijing Municipal Administration of Hospitals Clinical Medicine Development of Special Funding Support“Yanfan”Project,No.ZYLX201802.
文摘BACKGROUND Acute cholangitis is caused by bacterial infection and has high morbidity and mortality risk.The grade of cholangitis can guide clinical treatment from single antibiotic treatment to biliary drainage.With the introduction of white blood cell(WBC)count,C-reactive protein(CRP),and total bilirubin(T-Bil)into the diagnostic criteria and severity grading for acute cholangitis,the diagnosis rate and grading have significantly improved.However,early risk stratification assessments are challenging in the emergency department.Therefore,we hope to find an ideal predictive biomarker for cholangitis grade.Presepsin is a promising biomarker for the early diagnosis,severity,and prognosis of acute bacterial infections.AIM To assess the grading value of presepsin in patients with acute cholangitis.METHODS This clinical study was conducted at the Beijing Friendship Hospital,a 2000-bed teaching hospital with approximately 200000 emergency admissions per year.In this prospective observational study,336 patients with acute cholangitis meeting the Tokyo Guidelines 2018 diagnostic criteria in the emergency department from May 2019 to December 2020 were analyzed.WBC count,CRP,procalcitonin(PCT),presepsin,T-Bil,and blood culture results were collected.The values were compared using the Pearsonχ2 test,Fisher’s exact test,or Mann-Whitney U test.The area under the receiver operating characteristic curve(AUC)of the value was examined using the Delong test.The correlations among the key research indicators were determined using Pearson correlation.RESULTS In total,336 patients were examined,which included 107,106,and 123 patients classified as having mild,moderate,and severe cholangitis,respectively.WBC count,CRP,PCT,presepsin,T-Bil,direct bilirubin,and sequential organ failure assessment scores of moderate and severe cholangitis patients were higher than those of mild cholangitis patients(P=0.000).The AUC of presepsin in predicting moderate acute cholangitis was 0.728,which was higher than that of CRP(0.631,P=0.043)and PCT(0.585,P=0.002),and same as that of WBC count(0.746,P=0.713)and T-Bil(0.686,P=0.361).The AUC of presepsin in predicting severe acute cholangitis was 0.715,which was higher than that of WBC count(0.571,P=0.008),CRP(0.590,P=0.009),PCT(0.618,P=0.024),and T-Bil(0.559,P=0.006).The presepsin levels in the positive blood culture group were higher(2830.8pg/mLvs1987.8pg/mL,P=0.000),and the AUC of presepsin(0.688)proved that it was a good biomarker for predicting positive bacterial culture.CONCLUSION Presepsin can predict positive blood culture in patients with acute cholangitis.It is superior to WBC count,CRP,PCT,and T-Bil for the risk stratification of acute cholangitis.
基金This work was supported by the National Natural Science Foundation of China(81773931 and 81374004)as well as the Beijing Municipal Administration of Hospitals Clinical Medicine Development of Special Funding Support“YangFan”Project(ZYLX201802).
文摘Dear editor,Herpes B virus(BV),also known as Macacine herpesvirus 1(family:Herpesviridae,subfamily:Alphaherpesvirinae,genus:Simplexvirus),officially designated by the International Committee on the Taxonomy of Viruses,exhibits serologic cross-reactivity with other members of the genus Simplexvirus,namely HSV type 1(HSV-1),the causative agent of oral herpetic ulcers(cold sores)in humans and HSV type 2(HSV-2),the agent of human genital herpes.[1]
基金Supported by Beijing Municipal Administration of Hospitals Clinical Medicine Development of Special Funding Support “Yangfan” Project,No.ZYLX201802Beijing Municipal Administration of Hospitals’ Youth Program,No.QML20170105National Natural Science Foundation of China,No.81374004 and 81773931
文摘BACKGROUND Acute pancreatitis(AP) is an inflammatory disorder of the pancreas with an unpredictable course of illness. A major challenge of AP is the early identification of patients at high-risk for organ failure and death. However, scoring systems are complicated and time consuming, and the predictive values for the clinical course are vague.AIM To determine whether the dynamic changes in presepsin levels can be used to evaluate the severity of disease and outcome of AP.METHODS In this multicentric cohort study, 133 patients with AP were included. Clinical severity was dynamically evaluated using the 2012 revised Atlanta Classification. Blood presepsin levels were measured at days 1, 3, 5 and 7 after admission by chemiluminescent enzyme immunoassay.RESULTS The median concentration of presepsin increased and the clearance rate of presepsin decreased with disease severity and organ failure in AP patients. The presepsin levels on days 3, 5 and 7 were independent predictors of moderately severe and severe AP with time-specific area under the curve(AUC) values of 0.827, 0.848 and 0.867, respectively. The presepsin levels positively correlated with bedside index of severity in AP, Ranson, acute physiology and chronic health evaluation II, computed tomography severity index and Marshall scores. Presepsin levels on days 3, 5 and 7 were independent predictors of 28-d mortality of AP patients with AUC values of 0.781, 0.846 and 0.843, respectively.CONCLUSION Blood presepsin levels within 7 d of admission were associated with and may be useful to dynamically predict the severity of disease course and 28-d mortality in AP patients.
文摘BACKGROUND:This study aimed to explore the changes of programmed death-ligand 1(PDL1)and programmed death-1(PD-1)expression on antigen-presenting cells(APCs)and evaluate their association with organ failure and mortality during early sepsis.METHODS:In total,40 healthy controls and 198 patients with sepsis were included in this study.Peripheral blood was collected within the first 24 h after the diagnosis of sepsis.The expression of PDL1 and PD-1 was determined on APCs,such as B cells,monocytes,and dendritic cells(DCs),by flow cytometry.Cytokines in plasma,such as interferon-γ(IFN-γ),tumor necrosis factor-α(TNF-α),interleukin-4(IL-4),IL-6,IL-10,and IL-17A were determined by Luminex assay.RESULTS:PD-1 expression decreased significantly on B cells,monocytes,myeloid DCs(mDCs),and plasmacytoid DCs(pDCs)as the severity of sepsis increased.PD-1 expression was also markedly decreased in non-survivors compared with survivors.In contrast,PD-L1 expression was markedly higher on mDCs,pDCs,and monocytes in patients with sepsis than in healthy controls and in non-survivors than in survivors.The PD-L1 expression on APCs(monocytes and DCs)was weakly related to organ dysfunction and infl ammation.The area under the receiver operating characteristic curve(AUC)of the PD-1 percentage of monocytes(monocyte PD-1%)+APACHE II model(0.823)and monocyte PD-1%+SOFA model(0.816)had higher prognostic value than other parameters alone.Monocyte PD-1%was an independent risk factor for 28-day mortality.CONCLUSION:The severity of sepsis was correlated with PD-L1 or PD-1 over-expression on APCs.PD-L1 in monocytes and DCs was weakly correlated with infl ammation and organ dysfunction during early sepsis.The combination of SOFA or APACHE II scores with monocyte PD-1%could improve the prediction ability for mortality.
基金National Natural Science Foundation of China,No.81773931Beijing Municipal Administration of Hospitals’ Youth Program,No.QML20170105Beijing Municipal Administration of Hospitals Clinical Medicine Development of Special Funding Support "Yangfan" Project,No.ZYLX201804
文摘BACKGROUND Bacteremia,which is a major cause of mortality in patients with acute cholangitis,induces hyperactive immune response and mitochondrial dysfunction.Presepsin is responsible for pathogen recognition by innate immunity.Acylcarnitines are established mitochondrial biomarkers.AIM To clarify the early predictive value of presepsin and acylcarnitines as biomarkers of severity of acute cholangitis and the need for biliary drainage.METHODS Of 280 patients with acute cholangitis were included and the severity was stratified according to the Tokyo Guidelines 2018.Blood presepsin and plasma acylcarnitines were tested at enrollment by chemiluminescent enzyme immunoassay and ultra-high-performance liquid chromatography-mass spectrometry,respectively.RESULTS The concentrations of presepsin,procalcitonin,short-and medium-chain acylcarnitines increased,while long-chain acylcarnitines decreased with the severity of acute cholangitis.The areas under the receiver operating characteristic curves(AUC)of presepsin for diagnosing moderate/severe and severe cholangitis(0.823 and 0.801,respectively)were greater than those of conventional markers.The combination of presepsin,direct bilirubin,alanine aminotransferase,temperature,and butyryl-L-carnitine showed good predictive ability for biliary drainage(AUC:0.723).Presepsin,procalcitonin,acetyl-L-carnitine,hydroxydodecenoyl-Lcarnitine,and temperature were independent predictors of bloodstream infection.After adjusting for severity classification,acetyl-L-carnitine was the only acylcarnitine independently associated with 28-d mortality(hazard ratio 14.396;P<0.001)(AUC:0.880).Presepsin concentration showed positive correlation with direct bilirubin or acetyl-L-carnitine.CONCLUSION Presepsin could serve as a specific biomarker to predict the severity of acute cholangitis and need for biliary drainage.Acetyl-L-carnitine is a potential prognostic factor for patients with acute cholangitis.Innate immune response was associated with mitochondrial metabolic dysfunction in acute cholangitis.
基金supported by grants from the National Natural Science Foundation of China(81773931 and 81374004)the Beijing Municipal Administration of Hospitals’Youth Program(QML20170105)+1 种基金the Natural Science Foundation of Beijing Municipality(7173253)the Beijing Municipal Administration of Hospitals Clinical Medicine Development of Special Funding Support“Yangfan”Project(ZYLX201802)。
文摘BACKGROUND:Acute pulmonary embolism(APE)with cardiac arrest(CA)is characterized by high mortality in emergency due to pulmonary arterial hypertension(PAH).This study aims to determine whether early pulmonary artery remodeling occurs in PAH caused by massive APE with CA and the protective effects of increasing angiotensin-converting enzyme(ACE)2-angiotensin(Ang)(1-7)-Mas receptor axis and ACE-Ang II-Ang II type 1 receptor(AT1)axis(ACE2/ACE axes)ratio on pulmonary artery lesion after return of spontaneous circulation(ROSC).METHODS:To establish a porcine massive APE with CA model,autologous thrombus was injected into the external jugular vein until mean arterial pressure dropped below 30 mmHg(1 mmHg=0.133 kPa).Cardiopulmonary resuscitation and thrombolysis were delivered to regain spontaneous circulation.Pigs were divided into four groups of five pigs each:control group,APE-CA group,ROSC-saline group,and ROSC-captopril group,to examine the endothelial pathological changes and expression of ACE2/ACE axes in pulmonary artery with or without captopril.RESULTS:Histological analysis of samples from the APE-CA and ROSC-saline groups showed that pulmonary arterioles were almost completely occluded by accumulated endothelial cells.Western blotting analysis revealed a decrease in the pulmonary arterial ACE2/ACE axes ratio and increases in angiopoietin-2/angiopoietin-1 ratio and expression of vascular endothelial growth factor(VEGF)in the APE-CA group compared with the control group.Captopril significantly suppressed the activation of angiopoietin-2/angiopoietin-1 and VEGF in plexiform lesions formed by proliferative endothelial cells after ROSC.Captopril also alleviated endothelial cell apoptosis by increasing the B-cell lymphoma-2(Bcl-2)/Bcl-2-associated X(Bax)ratio and decreasing cleaved caspase-3 expression.CONCLUSION:Increasing the ACE2/ACE axes ratio may ameliorate pulmonary arterial remodeling by inhibiting the apoptosis and proliferation of endothelial cells after ROSC induced by APE.
基金Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences(No.2019-I2M-5-023)Hainan Provincial Science and Technology Major Project(No.ZDKJ201804)+2 种基金National Natural Science Foundation of China(No.81871611)National Natural Science Foundation of China(No.81760352)Project of Hainan Provincial Department of Education(No.Hnjg2019ZD-16)
文摘1.Introduction Sudden cardiac death(SCD)refers to sudden death due to a variety of cardiac causes.It is manifested as a sudden loss of consciousness,cardiac arrest,and respiratory arrest and generally shows early symptoms that are atypical and not easily detected[1].According to a recent study,nearly 544000 patients suffer from SCD every year in China[2].
