Development Of Multiorgan Dysfunction Syndrome Research Articles

Targeting ferroptosis protects against experimental (multi)organ dysfunction and death

The most common cause of death in the intensive care unit (ICU) is the development of multiorgan dysfunction syndrome (MODS). Besides life-supporting treatments, no cure exists, and its mechanisms are still poorly understood. Catalytic iron is associated with ICU mortality and is known to cause free radical-mediated cellular toxicity. It is thought to induce excessive lipid peroxidation, the main characteristic of an iron-dependent type of cell death conceptualized as ferroptosis. Here we show that the severity of multiorgan dysfunction and the probability of death are indeed associated with plasma catalytic iron and lipid peroxidation. Transgenic approaches underscore the role of ferroptosis in iron-induced multiorgan dysfunction. Blocking lipid peroxidation with our highly soluble ferrostatin-analogue protects mice from injury and death in experimental non-septic multiorgan dysfunction, but not in sepsis-induced multiorgan dysfunction. The limitations of the experimental mice models to mimic the complexity of clinical MODS warrant further preclinical testing. In conclusion, our data suggest ferroptosis targeting as possible treatment option for a stratifiable subset of MODS patients.

Early postoperative mortality in liver transplant recipients involving indications other than hepatocellular carcinoma. A retrospective cohort study

AimsTo analyze the perioperative differences in a consecutive cohort of liver transplant recipients (LTRs) classified according to the indication of transplantation, and assess their impact upon early mortality 90 days after transplantation. DesignA retrospective cohort study was carried out. ScopeA single university hospital. PatientsA total of 892 consecutive adult LTRs were included from January 1995 to December 2017. Recipients with acute liver failure, retransplantation or with grafts from non-brain death donors were excluded. Two cohorts were analyzed according to transplant indication: hepatocellular carcinoma (HCC-LTR) versus non-carcinoma (non-HCC-LTR). Main variables of interestRecipient early mortality was the primary endpoint. The pretransplant recipient and donor characteristics, surgical time data and postoperative complications were analyzed as independent predictors. ResultsThe crude early postoperative mortality rate related to transplant indication was 13.3% in non-HCC-LTR and 6.6% in HCC-LTR (non-adjusted HR=2.12, 95%CI=1.25–3.60; p=0.005). Comparison of the perioperative features between the cohorts revealed multiple differences. Multivariate analysis showed postoperative shock (HR=2.02, 95%CI=1.26–3.24; p=0.003), early graft vascular complications (HR=4.01, 95%CI=2.45–6.56; p<0.001) and multiorgan dysfunction syndrome (HR=18.09, 95%CI=10.70–30.58; p<0.001) to be independent predictors of mortality. There were no differences in early mortality related to transplant indication (adjusted HR=1.60, 95%CI=0.93–2.76; p=0.086). ConclusionsThe crude early postoperative mortality rate in non-HCC-LTR was higher than in HCC-LTR, due to a greater incidence of postoperative complications with an impact upon mortality (shock at admission to intensive care and the development of multiorgan dysfunction syndrome).

Does Non-Neurologic Multiorgan Dysfunction After Out-of-Hospital Cardiac Arrest among Children Admitted in Coma Predict Outcome 1 Year Later?

In this article, we investigated whether non-neurologic multiorgan dysfunction syndrome (MODS) following out-of-hospital cardiac arrest (OHCA) predicts poor 12-month survival. We conducted a secondary data analysis of therapeutic hypothermia after pediatric cardiac arrest out-of-hospital randomized trial involving children who remained unconscious and intubated after OHCA ( n = 237). Associations between MODS and 12-month outcomes were assessed using multivariable logistic regression. Non-neurologic MODS was present in 95% of patients and sensitive (97%; 95% confidence interval [CI]: 93-99%) for 12-month survival but had poor specificity (10%; 95% CI: 4-21%). Development of non-neurologic MODS is not helpful to predict long-term neurologic outcome or survival after OHCA.

Early postoperative mortality in liver transplant recipients involving indications other than hepatocellular carcinoma. A retrospective cohort study

To analyze the perioperative differences in a consecutive cohort of liver transplant recipients (LTRs) classified according to the indication of transplantation, and assess their impact upon early mortality 90 days after transplantation. A retrospective cohort study was carried out. A single university hospital. A total of 892 consecutive adult LTRs were included from January 1995 to December 2017. Recipients with acute liver failure, retransplantation or with grafts from non-brain death donors were excluded. Two cohorts were analyzed according to transplant indication: hepatocellular carcinoma (HCC-LTR) versus non-carcinoma (non-HCC-LTR). Recipient early mortality was the primary endpoint. The pretransplant recipient and donor characteristics, surgical time data and postoperative complications were analyzed as independent predictors. The crude early postoperative mortality rate related to transplant indication was 13.3% in non-HCC-LTR and 6.6% in HCC-LTR (non-adjusted HR=2.12, 95%CI=1.25-3.60; p=0.005). Comparison of the perioperative features between the cohorts revealed multiple differences. Multivariate analysis showed postoperative shock (HR=2.02, 95%CI=1.26-3.24; p=0.003), early graft vascular complications (HR=4.01, 95%CI=2.45-6.56; p<0.001) and multiorgan dysfunction syndrome (HR=18.09, 95%CI=10.70-30.58; p<0.001) to be independent predictors of mortality. There were no differences in early mortality related to transplant indication (adjusted HR=1.60, 95%CI=0.93-2.76; p=0.086). The crude early postoperative mortality rate in non-HCC-LTR was higher than in HCC-LTR, due to a greater incidence of postoperative complications with an impact upon mortality (shock at admission to intensive care and the development of multiorgan dysfunction syndrome).

Fluid balance correlates with clinical course of multiple organ dysfunction syndrome and mortality in patients with septic shock.

IntroductionPositive fluid balance is a prognostic factor for mortality in patients with sepsis; however, the association between cumulated fluid balance (CFB) and sepsis-induced multi-organ dysfunction syndrome (MODS) has yet to be elucidated. In this study, we sought to determine whether CFB is correlated with MODS and mortality in cases of septic shock.MethodsThe study retrospectively recruited patients with septic shock from the intensive care unit of a tertiary care hospital. Multiple organ dysfunction syndrome (MODS) was identified as sequential organ failure assessment (SOFA) score ≥ 2 in more than one organ system. The CFB is the sum of all daily intake and output. An independent t-test, single and multivariate logistic regression, the receiver operating characteristic (ROC) curves, and the Pearson correlation coefficient were used to determine whether a relationship exists between CFB and the development of MODS and mortality.ResultsAmong the 104 patients enrolled in the study, 58 (55.8%) survived more than 28 days, and 73 (70.2%) developed MODS on day 3. The values of CFB in the first 24 hours and 72 hours after diagnosis of septic shock in patients with MODS were higher than these in patients without MODS (1086.6 ± 176.3 vs. 325.5 ± 205.7 ml, p = 0.013 and 2408 ± 361 vs. 873.1 ± 489 ml, p < 0.0001). In a multivariate logistic regression, the independent factors associated with the development of MODS on day 3 were APACHE II score at ICU admission (27.6 ± 7.6 in patients with MODS vs. 20.5 ± 6.4 in those without; O.R. 1.18; 95% C.1 I. 1.08–1.30; p < 0.001), disseminated intravascular coagulopathy (DIC) (n = 28; 38.4% vs. n = 2; 6.5%; O.R. 23.67; 95% C.I. 3.58–156.5; p = 0.001), and CFB in the first 72 hours (72-hr CFB) > median (1767.50ml) (n = 41; 56.2% vs. n = 11; 35.5%; O.R. 3.67; 95% C.I., 1.18–11.40; p = 0.024). Moreover, a multivariate logistic regression also identified neoplasm (n = 25; 54.3% vs. n = 17; 29.3%; O.R. 3.45; 95% C.I. 1.23–10.0; p = 0.019) and 72-hr CFB > median (n = 30; 65.2% vs. n = 21; 36.2%; O.R. 4.13; 95% C.I. 1.34–12.66; p = 0.013) as independent factors associated with 28-day mortality. 72-hr CFB values were strongly correlated with the SOFA score (r = 0.445, p < 0.0001). The area under the ROC curve revealed that 72-hr CFB has good discriminative power in associating the development of MODS (0.644, p = 0.002) and predicting subsequent 28-day mortality (0.704, p < 0.0001).Conclusions72-hr CFB appears to be correlated with the likelihood of developing MODS and mortality in patients with septic shock. Thus, it appears that 72-hr CFB could perhaps be used as an indicator for MODS and a predictor for mortality in those patients.

Machine learning for the detection of early immunological markers as predictors of multi-organ dysfunction

The immune response to major trauma has been analysed mainly within post-hospital admission settings where the inflammatory response is already underway and the early drivers of clinical outcome cannot be readily determined. Thus, there is a need to better understand the immediate immune response to injury and how this might influence important patient outcomes such as multi-organ dysfunction syndrome (MODS). In this study, we have assessed the immune response to trauma in 61 patients at three different post-injury time points (ultra-early (<=1 h), 4–12 h, 48–72 h) and analysed relationships with the development of MODS. We developed a pipeline using Absolute Shrinkage and Selection Operator and Elastic Net feature selection methods that were able to identify 3 physiological features (decrease in neutrophil CD62L and CD63 expression and monocyte CD63 expression and frequency) as possible biomarkers for MODS development. After univariate and multivariate analysis for each feature alongside a stability analysis, the addition of these 3 markers to standard clinical trauma injury severity scores yields a Generalized Liner Model (GLM) with an average Area Under the Curve value of 0.92 ± 0.06. This performance provides an 8% improvement over the Probability of Survival (PS14) outcome measure and a 13% improvement over the New Injury Severity Score (NISS) for identifying patients at risk of MODS.

Epigenetics Mechanisms in Multiorgan Dysfunction Syndrome.

Epigenetic mechanisms including deoxyribonucleic acid (DNA) methylation, histone modifications (eg, histone acetylation), and microribonucleic acids (miRNAs) have gained much scientific interest in the last decade as regulators of genes expression and cellular function. Epigenetic control is involved in the modulation of inflammation and immunity, and its dysregulation can contribute to cell damage and organ dysfunction. There is growing evidence that epigenetic changes can contribute to the development of multiorgan dysfunction syndrome (MODS), a leading cause of mortality in the intensive care unit (ICU). DNA hypermethylation, histone deacetylation, and miRNA dysregulation can influence cytokine and immune cell expression and promote endothelial dysfunction, apoptosis, and end-organ injury, contributing to the development of MODS after a critical injury. Epigenetics processes, particularly miRNAs, are emerging as potential biomarkers of severity of disease, organ damage, and prognostic factors in critical illness. Targeting epigenetics modifications can represent a novel therapeutic approach in critical care. Inhibitors of histone deacetylases (HDCAIs) with anti-inflammatory and antiapoptotic activities represent the first class of drugs that reverse epigenetics modifications with human application. Further studies are required to acquire a complete knowledge of epigenetics processes, full understanding of their individual variability, to expand their use as accurate and reliable biomarkers and as safe target to prevent or attenuate MODS in critical disease.

Metabolomics analysis of gut barrier dysfunction in a trauma-hemorrhagic shock rat model

Intestinal barrier dysfunction has been implicated in the development of multiorgan dysfunction syndrome caused by the trauma-hemorrhagic shock (THS). However, the mechanisms underlying THS-induced gut barrier injury are still poorly understood. In the present study, we used the metabolomics analysis to test the hypothesis that altered metabolites might be related to the development of THS-induced barrier dysfunction in the large intestine. Under the induction of THS, gut barrier failure was characterized by injury of permeability and mucus layer, which were companied by the decreased expression of zonula occludens-1 in the colon and increased levels of inflammatory factors including tumor necrosis factor-α, interferon-γ, interleukin (IL)-6, and IL-1β in the serum. A total of 16 differential metabolites were identified in colonic tissues from THS-treated rats compared with control rats. These altered metabolites included dihydroxy acetone phosphate, ribose-5-phosphate, fructose, glyceric acid, succinic acid, and adenosine, which are critical intermediates or end products that are involved in pentose phosphate pathway, glycolysis, and tricarboxylic acid cycle as well as mitochondrial adenosine triphosphate biosynthesis. These findings may offer important insight into the metabolic alterations in THS-treated gut injury, which will be helpful for developing effective metabolites-based strategies to prevent THS-induced gut barrier dysfunction.

Decreased high-density lipoprotein cholesterol level is an early prognostic marker for organ dysfunction and death in patients with suspected sepsis

PurposeWe sought to determine whether an early high-density lipoprotein cholesterol (HDL-C) measurement at emergency department (ED) admission is prognostic of multiorgan dysfunction syndrome (MODS) and death in a suspected sepsis cohort. Materials and MethodsTwo hundred patients with clinically suspected sepsis were recruited at admission to our tertiary care hospital's ED. Lipids were measured at the time of first ED blood draw. Clinical data were collected via chart review. Primary outcomes of interest were development of MODS and 28-day mortality. Secondary outcomes included need for critical care, single-organ failures, days alive and free of vasopressor and ventilator support, and 90-day mortality. ResultsHigh-density lipoprotein cholesterol was greatly decreased in patients who developed MODS and/or died and remained stable over the first week of admission. Receiver operator characteristic analysis demonstrated that HDL-C had superior predictive ability compared with all routine clinical markers for both development of MODS and 28-day mortality, and identified an HDL-C cutoff of 25.1 mg/dL below which patients were at significantly greater risk for development of all adverse outcomes. ConclusionsPlasma HDL-C level was characterized by early decrease and high stability, and was the best prognostic marker for adverse outcomes in a suspected sepsis cohort.

Effect of inflammatory mediators on cardiovascular function.

Inflammatory mediators can interfere with cardiovascular system. This article describes some recent findings in this field. In septic cardiomyopathy, direct and indirect interactions of endotoxin with the pacemaker current contribute to cardiac autonomic dysfunction and inadequately high heart rate, worsening prognosis. In myocardial infarction, inflammatory blood cells correlate with impaired coronary microvascular reperfusion. In cardiogenic shock, systemic inflammation and development of multiorgan dysfunction syndrome have a major impact on mortality. Shock patients have low levels of activated protein C and high levels of the endogenous danger signal molecule peroxiredoxin 1; both conditions might represent further therapeutic targets. As major cause of cytopathic hypoxia, mitochondrial dysfunction has also been identified in mitochondria from peripheral blood mononuclear cells in paediatric septic shock. Transcatheter aortic valve endocarditis, a new endocarditis entity after transcatheter aortic valve implantation in old and very old patients, needs our special attention, because immunosenescence may modify the clinical course in a negative sense. Systemic spreading of endocarditis to septic shock adds to the local valve infection the problem of septic shock. Not only in septic shock, but also in classic heart diseases like cardiogenic shock and endocarditis, the detrimental role of inflammatory mediators becomes more and more evident, whereas effective anti-inflammatory treatment concepts are still missing.

Pathogenesis of Multiple Organ Failure in Sepsis.

Sepsis is a severe critical illness syndrome that arises from infectious insults. While the host immune system is generally beneficial, an overshooting and unregulated immune response can cause serious organ tissue injury. During sepsis, systemic hypotension, disturbed perfusion of the microcirculation, and direct tissue-toxicity caused by inflammatory immune reaction can occur and contribute to organ failure. The failure of two or more vital organ systems is termed multi-organ dysfunction syndrome (MODS) and resembles a very critical condition associated with high morbidity and mortality. Importantly, no specific treatment strategy exists to efficiently prevent the development of MODS during sepsis. In this review, we aim to identify the relevant molecular immunological pathways involved in the pathogenesis of MODS during sepsis. We believe that a detailed understanding of this mechanism is necessary for the development of new treatment approaches for septic patients. In particular, knowledge of the endogenous regulators keeping the balance between necessary immune system activation to combat infections and prevention of host tissue damage would greatly improve the chances for the development of effective interventions.

Thrombomodulin is a Strong Predictor of Multiorgan Dysfunction Syndrome in Patients With Sepsis

Biomarkers of endothelial dysfunction are not recommended for routine laboratory investigation of the outcome prognosis and prediction of the course of sepsis. A total of 60 patients who fulfilled the criteria for diagnosis of sepsis were included in our study. Development of multiorgan dysfunction syndrome (MODS) in the first 48 hours was assessed. Differences between groups of patients with sepsis were assessed by Mann-Whitney U test and by Kruskal-Wallis test. Logistic regression analysis was performed to test the joint effect of different predictors. Level of thrombomodulin was significantly higher in group of patients with MODS than without MODS (P = .015). Levels of antithrombin (P = .026) and protein C (P = .035) were significantly lower in patients with MODS. Level of thrombomodulin was the strongest predictor in MODS development in first 48 hours (P = .028). The level of thrombomodulin not only was able to distinguish the severity of sepsis but also was a significant predictor of MODS development.

Influence of genetic variability at the surfactant proteins A and D in community-acquired pneumonia: a prospective, observational, genetic study.

IntroductionGenetic variability of the pulmonary surfactant proteins A and D may affect clearance of microorganisms and the extent of the inflammatory response. The genes of these collectins (SFTPA1, SFTPA2 and SFTPD) are located in a cluster at 10q21-24. The objective of this study was to evaluate the existence of linkage disequilibrium (LD) among these genes, and the association of variability at these genes with susceptibility and outcome of community-acquired pneumonia (CAP). We also studied the effect of genetic variability on SP-D serum levels.MethodsSeven non-synonymous polymorphisms of SFTPA1, SFTPA2 and SFTPD were analyzed. For susceptibility, 682 CAP patients and 769 controls were studied in a case-control study. Severity and outcome were evaluated in a prospective study. Haplotypes were inferred and LD was characterized. SP-D serum levels were measured in healthy controls.ResultsThe SFTPD aa11-C allele was significantly associated with lower SP-D serum levels, in a dose-dependent manner. We observed the existence of LD among the studied genes. Haplotypes SFTPA1 6A2 (P = 0.0009, odds ration (OR) = 0.78), SFTPA2 1A0 (P = 0.002, OR = 0.79), SFTPA1-SFTPA2 6A2-1A0 (P = 0.0005, OR = 0.77), and SFTPD-SFTPA1-SFTPA2 C-6A2-1A0 (P = 0.00001, OR = 0.62) were underrepresented in patients, whereas haplotypes SFTPA2 1A10 (P = 0.00007, OR = 6.58) and SFTPA1-SFTPA2 6A3-1A (P = 0.0007, OR = 3.92) were overrepresented. Similar results were observed in CAP due to pneumococcus, though no significant differences were now observed after Bonferroni corrections. 1A10 and 6A-1A were associated with higher 28-day and 90-day mortality, and with multi-organ dysfunction syndrome (MODS) and acute respiratory distress syndrome (ARDS) respectively. SFTPD aa11-C allele was associated with development of MODS and ARDS.ConclusionsOur study indicates that missense single nucleotide polymorphisms and haplotypes of SFTPA1, SFTPA2 and SFTPD are associated with susceptibility to CAP, and that several haplotypes also influence severity and outcome of CAP.

Prognostic value of procalcitonin (PCT) and/or interleukin-6 (IL-6) plasma levels after multiple trauma for the development of multi organ dysfunction syndrome (MODS) or sepsis

Despite recent advances in treatment of severe injured patients, e.g. due to damage control orthopaedics, multi organ dysfunction syndrome (MODS) and sepsis are major complications in daily practice. During one year 94 patients were prospectively collected. ISS 16, age 18-60 y, primary admission to our level-1 trauma center, survival > 48 hours after trauma. The development of MODS and sepsis were observed and different groups were formed (+/-). Demographic data revealed no significant differences between the subgroups. Comparing groups +MODS and -MODS significant differences on admission day were observed, when PCT showed first on day 2 after trauma differences. Regarding the development of sepsis PCT was advantageous to IL-6 showing significant higher plasma levels in group +sepsis from the first day after trauma. Serum levels of IL-6 and PCT could be useful in early identification of high risk patients to develop posttraumatic MODS. For sepsis PCT is the better prognostic factor.

Development of Klebsiella pneumoniae B5055-induced mouse model of sepsis-associated brain inflammation in BALB/c mice

Incidence of sepsis is continuously increasing in the developing as well as the developed world. Severe sepsis is associated with the development of multiorgan dysfunction syndrome. In addition to other vital organs (that is, lungs, kidneys, heart, or liver), the brain is one of the severely affected organs in sepsis. Autopsy studies from septic patients reveal various cerebral lesions including ischemia, hemorrhage, microthrombi, microabscesses, multifocal necrotizing leukoencephalopathy, and bacterial invasion of the nervous system. Until now no animal model of sepsis has been developed that in a true sense represents the brain inflammation associated with evolving sepsis originating from Gram-negative bacteria. This study comprises development of a mouse model of sepsis-induced brain inflammation.

Gastric tonometry as a prognostic index of mortality in sepsis

Background: Splanchnic hypoperfusion in sepsis leads to translocation of bacteria from gut and development of multi-organ dysfunction syndrome (MODS), with increased mortality in critically ill patients. Gastric tonometry can detect this hypoperfusion by measuring carbon dioxide tension (PgCO 2) and intramucosal pH (pHi) from gastric mucosa. Therapeutic intervention aimed at improving gut perfusion can improve the outcome and prognosticate the mortality in sepsis patients. Methods: 100 patients with clinical diagnosis of sepsis were included and divided into two groups of 50 each. Group A patients were managed traditionally without gastric tonometry and in Group B gastric tonometry was used for therapeutic intervention. The intramucosal PCO 2, pHi, end tidal carbon dioxide tension (EtCO 2) and (PgCO 2-EtCO 2) differences were monitored at 0, 12 and 24 hours interval. Result: Overall mortality in Group A was 64% and 54% in Group B. In Group B 45% patients developed MODS and 54% died with low pHi. As an index of mortality low pHi had a sensitivity of 70% and specificity of 65%. Conclusion: There is a good correlation between mortality prediction on the basis of pHi and PgCO 2-EtCO 2 difference and actual mortality in critically ill patients. The gastric tonometer should be used to predict mortality and guide resuscitation in septicemia.

Analysis of risk factors for hospital mortality in patients with chronic obstructive pulmonary diseases requiring invasive mechanical ventilation

Accurate prediction for prognosis is important for hospitalized patients with chronic obstructive pulmonary disease (COPD) requiring invasive mechanic ventilation (IMV) and for their family members to make end-of-life decisions. The response to therapy in such a patient population has rarely been investigated. The aim of the study was to evaluate the risk factors in these patients and investigate their response to IMV and the relationship between their responses and prognosis. A cohort of 138 patients with COPD requiring IMV >or= 12 hours for acute respiratory failure of diverse etiological factors during a 4-year period were retrospectively studied using prospectively gathered data. All variables potentially related to hospital mortality were evaluated by univariate and multiple stepwise logistic regression analysis. The mean age of all patients investigated was (65.7 +/- 11.6) years and the hospital mortality was 39.9% (31.1% with COPD exacerbation). Correction of acidosis (pH >or= 7.30) was seen in 58 patients (69.9%) in survivors but only 12 patients (21.8%) in nonsurvivors (P < 0.05) after ventilation. Using multivariate logistic analysis, the variables independently associated with hospital mortality were a higher acute physiology score before intubation, lower pH value measured 24 hours after the onset of ventilation and development of multiorgan dysfunction syndrome (MODS). In COPD patients requiring IMV, the postintubation pH value can not only reflect patients' response to treatment, but also serve as an independent determinant of hospital mortality apart from other risk factors such as a higher preintubation APACHE II score and development of MODS. A close correlation between the response to IMV and prognosis was proved in these patients.

Identification of severe acute pancreatitis using an artificial neural network

The aim of this study was to construct and validate an artificial neural network (ANN) model to identify severe acute pancreatitis (AP) and predict fatal outcome. All patients who presented with AP from January 2000 to September 2004 were reviewed. Presentation data on admission and at 48 hours were collected. Acute Physiology and Chronic Health Evaluation (APACHE) II and Glasgow severity (GS) score were calculated. A feed-forward ANN was created and trained to predict development of severe AP and mortality from AP; 25% of the data set was withheld from training and was used to evaluate the accuracy of the ANN. Accuracy of the ANN in predicting severity of AP was compared with APACHE II and GS scores. A total of 664 patients with AP were identified of whom 181 (27.3%) fulfilled the clinical and radiologic criteria for severe pancreatitis and 42 patients died (6.3%). Median APACHE II score at 48 hours was 4 (range, 0 to 23). ANN was more accurate than APACHE II or GS scoring systems at predicting progression to a severe course (P < .05 and P < .01, respectively), predicting development of multiorgan dysfunction syndrome (P < .05 and P < .01) and at predicting death from AP (P < .05). An ANN was able to predict progression to severe disease, development of organ failure and mortality from acute pancreatitis with considerable accuracy and outperformed other clinical risk scoring systems. Further studies are required to assess its utility in aiding management decisions in patients with AP.

Association between early systemic inflammatory response, severity of multiorgan dysfunction and death in acute pancreatitis

Mortality in patients with acute pancreatitis is associated with the number of failing organs and the severity and reversibility of organ dysfunction. The aim of this study was to assess the significance of early systemic inflammatory response syndrome (SIRS) in the development of multiorgan dysfunction syndrome (MODS) and death from acute pancreatitis. Data for all patients with a diagnosis of acute pancreatitis between January 2000 and December 2004 were reviewed. Serum C-reactive protein (CRP), Acute Physiology And Chronic Health Evaluation (APACHE) II scores and presence of SIRS were recorded on admission and at 48 h. Marshall organ dysfunction scores were calculated during the first week of presentation. Presence of SIRS and raised serum CRP levels on admission and at 48 h were correlated with the cumulative organ dysfunction scores in the first week. A total of 759 patients with acute pancreatitis were identified, of whom 45 (5.9 per cent) died during the index admission. SIRS was identified in 162 patients on admission and was persistent in 138 at 48 h. The median (range) cumulative Marshall score in patients with persistent SIRS was significantly higher than that in patients in whom SIRS resolved and in those with no SIRS (4 (0-12), 3 (0-7) and 0 (0-9) respectively; P < 0.001). Thirty-five patients (25.4 per cent) with persistent SIRS died from acute pancreatitis, compared with six patients (8 per cent) with transient SIRS and four (0.7 per cent) without SIRS (P < 0.001). No correlation was observed between CRP level on admission and Marshall score (P = 0.810); however, there was a close correlation between CRP level at 48 h and Marshall score (P < 0.001). Persistent SIRS is associated with MODS and death in patients with acute pancreatitis and is an early indicator of the likely severity of acute pancreatitis.

The contribution of radiation-induced injury to the gastrointestinal tract in the development of multi-organ dysfunction syndrome or failure

Severe damage to the gastrointestinal tract (GIT), such as loss of the gastrointestinal mucosa and haemorrhage, following accidental overexposure to ionising radiation appears to be a determinant feature in patient mortality. Injury to the GIT may be direct, as this tissue is particularly radiation sensitive, as well as indirect as a result of radiation burns and bone marrow aplasia. Similar to other severe trauma situations such as thermal burns, radiation exposure results in reduced intestinal barrier integrity, which initiates and/or perpetuates inflammatory–anti-inflammatory mediator release. This may result in damage to distant organs. In this context, the injured gut may be considered as a “key player” or “motor” in the development of multiple organ dysfunction syndrome or failure. Of note is that radiation exposure elicits similar GIT injury of both mucosal and vascular elements, in contrast to other severe physical insults. Common factors are the intestinal inflammatory response and loss of barrie...