Acute pancreatitis(AP)is a heterogeneous inflammatory condition.Although emerging therapeutic strategies targeting pathways such as calcium signaling,TNF-α,the NLRP3 inflammasome,and HMGB1 have shown promise,their ef...Acute pancreatitis(AP)is a heterogeneous inflammatory condition.Although emerging therapeutic strategies targeting pathways such as calcium signaling,TNF-α,the NLRP3 inflammasome,and HMGB1 have shown promise,their efficacy may be limited by the underlying biological heterogeneity of the disease.In this multinational retrospective cohort study across three large ICU databases(ICU-HAI,MIMIC-IV,and eICU-CRD),we used group-based trajectory modeling of early vital signs to identify four distinct AP subphenotypes:hyperinflammatory,hypertensive,hypotensive,and hypoinflammatory.These subtypes differed markedly in 30-day mortality,inflammatory burden,and hemodynamic stability.Compared to the hypertensive phenotype,hyperinflammatory and hypotensive patients had significantly higher 30-day mortality risks(HR=3.38 and HR=1.87,respectively),while the hypoinflammatory phenotype carried no excess risk.Fluid resuscitation responses were phenotype-specific:hyperinflammatory patients benefited from higher fluid volumes,whereas hypoinflammatory patients were at risk of fluid overload.Notably,distinct subphenotypes displayed unique responses to fluid intake over the first two ICU days.For hyperinflammatory phenotype,the algorithm-estimated lowest-risk fluid range was 4100-4300 mL on day 1 and 3400-3600 mL on day 2;for phenotype hypoinflammatory phenotype,the optimal ranges were 2800-3800 mL and 1400-2600 mL,respectively.Early use of lactated Ringer’s solution,which inhibited NLRP3,was associated with reduced mortality in hypotensive phenotype.These findings underscore the clinical relevance of early physiological trajectories and support precision fluid resuscitation based on subtype.This study establishes the largest early-trajectory-based classification of AP to date,offering new insights into immune and vascular mechanisms that drive heterogeneity and therapeutic responsiveness.展开更多
Beta blockers(BB)are widely used for the treatment of cardiovascular diseases to reduce heart rate and hence the myocardial oxygen consumption[1].Of note,studies found BB may confer clinical benefits in critically ill...Beta blockers(BB)are widely used for the treatment of cardiovascular diseases to reduce heart rate and hence the myocardial oxygen consumption[1].Of note,studies found BB may confer clinical benefits in critically ill patients,though confirmatory evidence is still lacking.展开更多
基金funded by the National Natural Science Foundation of China(Grant Nos.82225049,72104155,and 72304198)the 1·3·5 Project for Disciplines of Excellence,West China Hospital,Sichuan University(Grant No.ZYGD23004).
文摘Acute pancreatitis(AP)is a heterogeneous inflammatory condition.Although emerging therapeutic strategies targeting pathways such as calcium signaling,TNF-α,the NLRP3 inflammasome,and HMGB1 have shown promise,their efficacy may be limited by the underlying biological heterogeneity of the disease.In this multinational retrospective cohort study across three large ICU databases(ICU-HAI,MIMIC-IV,and eICU-CRD),we used group-based trajectory modeling of early vital signs to identify four distinct AP subphenotypes:hyperinflammatory,hypertensive,hypotensive,and hypoinflammatory.These subtypes differed markedly in 30-day mortality,inflammatory burden,and hemodynamic stability.Compared to the hypertensive phenotype,hyperinflammatory and hypotensive patients had significantly higher 30-day mortality risks(HR=3.38 and HR=1.87,respectively),while the hypoinflammatory phenotype carried no excess risk.Fluid resuscitation responses were phenotype-specific:hyperinflammatory patients benefited from higher fluid volumes,whereas hypoinflammatory patients were at risk of fluid overload.Notably,distinct subphenotypes displayed unique responses to fluid intake over the first two ICU days.For hyperinflammatory phenotype,the algorithm-estimated lowest-risk fluid range was 4100-4300 mL on day 1 and 3400-3600 mL on day 2;for phenotype hypoinflammatory phenotype,the optimal ranges were 2800-3800 mL and 1400-2600 mL,respectively.Early use of lactated Ringer’s solution,which inhibited NLRP3,was associated with reduced mortality in hypotensive phenotype.These findings underscore the clinical relevance of early physiological trajectories and support precision fluid resuscitation based on subtype.This study establishes the largest early-trajectory-based classification of AP to date,offering new insights into immune and vascular mechanisms that drive heterogeneity and therapeutic responsiveness.
基金supported by Jiangsu Province Traditional Chinese Medicine Technology Development Plan Project(QN202305)National Natural Science Foundation of China(82474636).
文摘Beta blockers(BB)are widely used for the treatment of cardiovascular diseases to reduce heart rate and hence the myocardial oxygen consumption[1].Of note,studies found BB may confer clinical benefits in critically ill patients,though confirmatory evidence is still lacking.
