Organ Dysfunction In Acute Pancreatitis Research Articles

Etiology and classification of acute pancreatitis in children admitted to ICU using the Pediatric Sequential Organ Failure Assessment (pSOFA) score

BackgroundPediatric acute pancreatitis (AP) is rare but increasing. Severe AP is associated with higher morbidity and mortality. However, there are no universally accepted prognostic criteria for AP. MethodsThis retrospective study included children with AP admitted to an intensive care unit (ICU) of our tertiary pediatric center between January 2009 and December 2018. The severity of organ dysfunction in AP was assessed according to the modified Atlanta criteria using the Pediatric Sequential Organ Failure Assessment (pSOFA) and Computed Tomography Severity Index (CTSI). ResultsSeventy acute episodes of AP were evaluated in 55 children with primary pancreatitis. In addition, secondary AP was diagnosed in 15 patients originally admitted to ICU for different indications. Mild AP [no organ dysfunction, normal computed tomography (CT) finding] was the most prevalent (64/85 episodes in 49 children), followed by moderate AP (15 children; pSOFA 2-9 points, CTSI 3-4 points on admission). Severe AP (pSOFA 4-17 points, CTSI 6-10 points) was diagnosed in 6 children with traumatic or secondary AP. The most frequent etiologies of primary AP episodes were idiopathic (39%) and biliary (31%). Children with idiopathic AP had frequent relapses and comorbidities. Hereditary AP was typically mild, but presented with high pancreatic enzyme levels and recurrence rates. Admission at ICU and an interval without enteral nutrition (EN) were relatively short in drug-induced AP and relatively long in secondary and traumatic AP. Endoscopic retrograde cholangiopancreatography (ERCP) was performed in 13 patients with biliary AP and in 4 patients with traumatic AP. No AP-related death was observed. ConclusionpSOFA score accurately reflects the severity and prognosis of AP in children.

Complement Component 3 Is Required for Tissue Damage, Neutrophil Infiltration, and Ensuring NET Formation in Acute Pancreatitis

Background: Neutrophil extracellular traps (NETs) are known to play an important role in the pathophysiology of acute pancreatitis (AP). Activation of the complement cascade has been shown to occur in AP. The aim of this study was to examine whether complement component 3 is involved in the generation of NETs in AP. Methods: AP was induced in wild-type and C3-deficient mice by retrograde infusion of taurocholate into the pancreatic duct. Blood, lung, and pancreas tissue were collected and MPO activity was determined in lung and pancreas tissue. Histological examination of the inflamed pancreas was performed. Plasma levels of CXCL2, MMP-9, IL-6, and DNA-histone complexes as well as pancreatic levels of CXCL1 and CXCL2 were determined by use of enzyme-linked immunosorbent assay. NETs were detected in the pancreas by electron microscopy. The amount of MPO and citrullinated histone 3 in neutrophils isolated from bone marrow was examined using flow cytometry. Results: In C3-deficient mice, challenge with taurocholate yielded much fewer NETs in the pancreatic tissue compared with wild-type controls. Taurocholate-induced blood levels of amylase, tissue injury, and neutrophil recruitment in the pancreas were markedly reduced in the mice lacking C3. Furthermore, MPO levels in the lung, and plasma levels of IL-6, MMP-9, and CXCL2 were significantly lower in the C3-deficient mice compared to wild-type mice after the induction of AP. In vitro studies revealed that neutrophils from C3-deficient mice had normal NET-forming ability and recombinant C3a was not capable of directly inducing NETs formation in the wild-type neutrophils. Conclusion: C3 plays an important role in the pathophysiology of AP as it is necessary for the recruitment of neutrophils into the pancreas and ensuring NETs formation. Targeting C3 could hence be a potential strategy to ameliorate local damage as well as remote organ dysfunction in AP.

Early organ dysfunction affects long-term survival in acute pancreatitis patients

BackgroundThe effect of early organ dysfunction on long-term survival in acute pancreatitis (AP) patients is unknown. ObjectiveThe aim of this study was to ascertain whether early organ dysfunction impacts on long-term survival after an episode of AP. MethodsA retrospective analysis was performed using survival data sourced from a prospectively maintained database of patients with AP admitted to the Royal Infirmary of Edinburgh during a 5-year period commencing January 2000. A multiple organ dysfunction syndrome (MODS) score of ≥2 during the first week of admission was used to define early organ dysfunction. After accounting for in-hospital deaths, long-term survival probabilities were estimated using the Kaplan–Meier test. The prognostic significance of patient characteristics was assessed by univariate and multivariate analyses using Cox's proportional hazards methods. ResultsA total of 694 patients were studied (median follow-up: 8.8 years). Patients with early organ dysfunction (MODS group) were found to have died prematurely [mean survival: 10.0 years, 95% confidence interval (CI) 9.4–10.6 years] in comparison with the non-MODS group (mean survival: 11.6 years, 95% CI 11.2–11.9 years) (log-rank test, P=0.001) after the exclusion of in-hospital deaths. Multivariate analysis confirmed MODS as an independent predictor of long-term survival [hazard ratio (HR): 1.528, 95% CI 1.72–2.176; P=0.019] along with age (HR: 1.062; P<0.001), alcohol-related aetiology (HR: 2.027; P=0.001) and idiopathic aetiology (HR: 1.548; P=0.048). ConclusionsEarly organ dysfunction in AP is an independent predictor of long-term survival even when in-hospital deaths are accounted for. Negative predictors also include age, and idiopathic and alcohol-related aetiologies.

Patients with acute pancreatitis complicated by organ dysfunction show abnormal peripheral blood polymorphonuclear leukocyte signaling

Background/objectivesCirculating polymorphonuclear leukocytes (PMNLs) may contribute to development of organ dysfunction in acute pancreatitis (AP). We outlined aberrations in PMNL signaling profiles in patients with AP complicated by organ dysfunction and immune suppression. MethodsStudy comprised 13 patients treated at intensive care unit due to severe AP complicated by vital organ dysfunction. Mean proportion (SEM) of HLA-DR-positive monocytes was 55.0% (4.1%). 13 healthy volunteers served as reference subjects. Phosphorylation of PMNL NFκB, p38, ERK1/2 and STAT3, -5 and -6 was determined using whole blood flow cytometry. Transmigration of PMNLs was studied using endothelial EA-HY cell monolayer. ResultsProportions of NFκB phosphorylation-positive PMNLs were lower in the patients' than in reference subjects' blood samples supplemented with tumor necrosis factor. p38 phosphorylation was normal while ERK1/2 phosphorylation was decreased. STAT3 was constitutively activated in five patients. Proportion of patients' pSTAT6-positive cells was normal while fluorescence intensity was decreased. STAT5 phosphorylation was normal. Transmigration of patients' PMNLs was increased. ConclusionsIn patients with AP complicated by organ dysfunction proportion of pNFκB-positive PMNLs is decreased. This impairs patients' defense mechanisms against infection. Despite immune suppression, PMNL transmigration was increased and p38 phosphorylation capacity was not depressed, which may contribute to end organ inflammation and dysfunction.

Effect of Ageing on Systemic Inflammatory Response in Acute Pancreatitis

Elderly patients show increased incidence of multiple organ dysfunction in acute pancreatitis possibly due to bacterial translocation. This is associated with increased susceptibility to infections in older people. Several reports have related this increased susceptibility to a proinflammatory status called inflammaging, which decreases the capacity of the immunological system to respond to antigens. Cellular senescence also contributes to this low-grade chronic inflammation in older subjects. We discuss here the effect of ageing on systemic inflammation, focusing on that induced by acute pancreatitis and some of the mechanisms involved. It is important to understand the immunological changes in the elderly to adjust treatment strategies in order to reduce the morbidity and mortality associated with acute pancreatitis and other conditions that lead to systemic inflammation.

Increased levels of soluble triggering receptor expressed on myeloid cells-1 in patients with acute pancreatitis*

To determine the contribution of triggering receptor expressed on myeloid cells (TREM)-1 in acute pancreatitis (AP). Prospective study. General intensive care unit at Kobe University Hospital. Forty-eight patients with AP and seven patients as control. None. We measured serum concentrations of soluble TREM-1 (sTREM-1) at the time of admission by enzyme-linked immunoadsorbent assay. Serum sTREM-1 levels increased significantly in AP (63 +/- 11 pg/mL) and correlated with Ranson score (R = .628, p < .001) and Acute Physiology and Chronic Health Evaluation II score (R = .504, p < .001). Serum TREM-1 levels were higher in patients with early organ dysfunction (which occurred within 7 days after onset) than those without early organ dysfunction (101 +/- 19 vs. 25 +/- 4 pg/mL, p < .001). Incidences of early organ dysfunction in patients whose serum sTREM-1 levels were < or = 40 and > 40 pg/mL were 17% and 83%, respectively (p < .001). The usefulness of serum sTREM-1 in detecting early organ dysfunction was superior to that of C-reactive protein, interleukin-6, interleukin-8, Ranson score, and Acute Physiology and Chronic Health Evaluation II score. Serum sTREM-1 levels decreased with resolution of early organ dysfunction. Serum sTREM-1 levels were significantly increased and correlated with disease severity and early organ dysfunction in patients with AP. Serum sTREM-1 level may be a useful marker for early organ dysfunction in AP.

CC-chemokine activation in acute pancreatitis: enhanced release of monocyte chemoattractant protein-1 in patients with local and systemic complications.

Systemic leukocyte activation is claimed to trigger inflammatory response and remote organ dysfunction in acute pancreatitis. Chemokines are inflammatory mediators with potent leukocyte-activating properties and have been shown to be involved in the pathophysiological process of experimental acute pancreatitis. However, as little is known about their role in human disease we investigated local and systemic concentrations of different CC-chemokine members in patients with acute pancreatitis. We included 68 patients with acute pancreatitis in the present study. Local complications in terms of necrosis were present in 37 (54%) patients of whom 21 (57%) developed pancreatic infections. Monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory protein-1alpha (MIP-1alpha) and macrophage inflammatory protein-1beta (MIP-1beta) concentrations were measured daily over 2 weeks after study inclusion by ELISA in sera and lesser sac aspirates. MCP-1 serum concentrations showed a dramatic increase in patients who developed local complications and/or remote organ failure. Herein, a close correlation was found between the severity of remote organ failure and the degree of MCP-1 elevation. Multiple regression analysis identified pancreatic infections as well as renal and cardiocirculatory failure as independent variables associated with enhanced systemic MCP-1 release. MIP-1alpha levels remained unaffected by local complications and showed a significant increase only; if multiple organ dysfunction syndrome (MODS) developed or patients subsequently died. In contrast, MIP-1beta concentrations correlated with neither the presence nor the severity of any complication. Compared with systemic concentrations, local lesser sac aspirates revealed significantly higher levels of MCP-1, whereas MIP-1alpha and MIP-1beta were not different. Complicated acute pancreatitis is associated with significantly elevated local and systemic concentrations of the CC-chemokine MCP-1. Our results suggest that, among the CC-chemokine members investigated, MCP-1 might play a pivotal role in the pathological mechanism of complicated acute pancreatitis.

Dynamic nature of early organ dysfunction determines outcome in acute pancreatitis

All patients with organ dysfunction are currently classified as having severe acute pancreatitis. The aim of this study was to characterize the systemic inflammatory response syndrome (SIRS) and early organ dysfunction in patients with acute pancreatitis and the relationship with overall mortality. Patients with predicted severe acute pancreatitis of less than 48 h duration had daily organ dysfunction scores and SIRS criteria calculated. These features were then correlated with outcome. Of 121 patients, 68 (56 per cent) did not develop organ dysfunction; only two of these patients died (mortality rate 3 per cent). Fifty-three (44 per cent) had early organ dysfunction, of whom 11 died (21 per cent). Organ dysfunction and persistent SIRS were both associated with an increased mortality rate, but on multivariate analysis only deteriorating organ dysfunction was an independent determinant of survival. Early organ dysfunction in acute pancreatitis usually resolves and in itself has no significant influence on mortality. In contrast, worsening organ dysfunction was associated with death in more than half of the patients (11 of 20); it is this group of patients who should be classified as having severe acute pancreatitis.

Endothelial-derived selectins in the development of organ dysfunction in acute pancreatitis.

The development of organ dysfunction is the principal determinant of outcome in acute pancreatitis and is mediated through a systemic inflammatory response characterized by leukocyte and endothelial cell activation. Up-regulation of the endothelial cell adhesion molecules, E-selectin and P-selectin, is important for endothelial/leukocyte interactions. Levels of serum-soluble E-selectin and P-selectin have been suggested as markers of endothelial activation. This study examines the kinetics of serum-soluble selectins in patients with acute pancreatitis complicated by organ dysfunction. Prospective observational study. University teaching hospital with a specialist hepato-pancreatico-biliary service. Eighteen patients with acute pancreatitis were studied, nine of whom had organ dysfunction. Serial venous blood samples were collected on the first 3 days after admission for measurement of soluble E-selectin and P-selectin by enzyme-linked immunosorbent assay. In all patients, soluble P-selectin concentrations decreased significantly during the study period. Nonsurvivors had significantly higher levels of soluble P-selectin than survivors. In contrast, soluble E-selectin increased significantly during the study period in patients with organ dysfunction, whereas it remained constant in patients without evidence of organ dysfunction. These results suggest a role for endothelial-derived selectins in the development of organ dysfunction in patients with acute pancreatitis. The observed temporal differences in serum selectin concentrations is in keeping with in vitro observations of endothelial selectin expression.

Inflammatory mediators in human acute pancreatitis: clinical and pathophysiological implications

BACKGROUNDThe time course and relationship between circulating and local cytokine concentrations, pancreatic inflammation, and organ dysfunction in acute pancreatitis are largely unknown.PATIENTS AND METHODSIn a prospective clinical study, we measured...

Persistent sirs precedes the development of early organ dysfunction in acute pancreatitis

Persistent sirs precedes the development of early organ dysfunction in acute pancreatitis

Monocyte production of nitric oxide (NO) in severe acute pancreatitis

To clarify the correlation between the kinetics of nitric oxide (NO) production and the occurrence of organ dysfunction in acute pancreatitis, we examined the production of NO2 and NO3 by monocytes in five patients with severe pancreatitis and organ dysfunction (four males and one female, aged 24–52 years: group S), and compared the results with those in five patients with mild pancreatitis (three males and two females, aged 24–52 years: group M) and 12 healthy volunteers (9 males and three females, aged 25–44: group C). The time course of induced NO production by cultured monocytes obtained from these subjects was also examined, using a NO-sensitive electrode. The levels of NO2 and NO3 production by monocytes in vitro, with or without stimulation, were significantly higher (P<0.05), the time required for NO production by cultured monocytes was significantly shorter (P<0.01), and the duration of NO production by monocytes was significantly longer (P<0.01), in group S compared with the other groups. These findings indicate that, in patients with severe acute pancreatitis, the NO-producing mechanism of monocytes is not only primed but also triggered. Further-more, it seems that NO production by monocytes is directly correlated with the incidence of organ dysfunction.