Predictors of Acute Respiratory Distress Syndrome in Patients with Paraquat Intoxication

Introduction

Paraquat poisoning is characterized by acute lung injury, pulmonary fibrosis, respiratory failure, and multi-organ failure, resulting in a high rate of mortality and morbidity. The objectives of this study were to identify predictors of acute respiratory distress syndrome (ARDS) in cases of paraquat poisoning and determine the association between these parameters.

Materials and Methods

In total, 187 patients were referred for management of intentional paraquat ingestion between 2000 and 2010. Demographic, clinical, and laboratory data were recorded. Sequential organ failure assessment (SOFA) and Acute Kidney Injury Network (AKIN) scores were collected, and predictors of ARDS were analyzed.

Results

The overall mortality rate for the entire population was 54% (101/187). Furthermore, the mortality rate was higher in the ARDS patients than in the non-ARDS patients (80% vs. 43.80%, P<0.001). Additionally, the ARDS patients not only had higher AKIN_48-h scores (P<0.009), SOFA_48-h scores (P<0.001), and time to ARDS/nadir PaO₂ (P=0.008) but also suffered from lower nadir PaO₂ (P<0.001), nadir AaDO₂ (P<0.001), and nadir eGFR (P=0.001) compared to those in the non-ARDS patients. Moreover, pneumomediastinum episodes were more frequent in the ARDS patients than in the non-ARDS patients (P<0.001). A multivariate Cox regression model revealed that blood paraquat concentrations (P<0.001), SOFA_48-h scores (P=0.001), and steroid and cyclophosphamide pulse therapies (P=0.024) were significant predictors of ARDS. The cumulative survival rates differed significantly (P<0.001) between patients with SOFA_48-h scores <3 and SOFA_48-h scores ≥3, with a sensitivity of 95.8%, specificity of 58.4%, and overall correctness of 67.6%. Finally, the area under the receiver operating characteristic (AUROC) analysis showed that SOFA_48-h scores (P<0.001) had a better discriminatory power than blood paraquat concentrations (P=0.01) for predicting ARDS.

Conclusions

The analytical results indicate that SOFA_48-h scores, blood paraquat concentrations, and steroid and cyclophosphamide pulse therapies are significantly associated with ARDS complications after paraquat intoxication.     

Predictors of mortality in patients successfully weaned from extracorporeal membrane oxygenation

Purpose

Extracorporeal membrane oxygenation (ECMO) has been utilized for critically ill patients, such as those with life-threatening respiratory failure or post-cardiotomy cardiogenic shock. This study compares the predictive value of Acute Physiology, Age, and Chronic Health Evaluation II (APACHE II), Sequential Organ Failure Assessment (SOFA), and Organ System Failure (OSF) obtained on the first day of ECMO removal, and the Acute Kidney Injury Network (AKIN) stages obtained at 48 hours post-ECMO removal (AKIN_48-hour) in terms of hospital mortality for critically ill patients.

Methods

This study reviewed the medical records of 119 critically ill patients successfully weaned from ECMO at the specialized intensive care unit of a tertiary-care university hospital between July 2006 and October 2010. Demographic, clinical, and laboratory data were collected retrospectively as survival predictors.

Results

Overall mortality rate was 26%. The most common condition requiring ECMO support was cardiogenic shock. By using the areas under the receiver operating characteristic (AUROC) curve, the Sequential Organ Failure Assessment (SOFA) score displayed good discriminative power (AUROC 0.805±0.055, p<0.001). Furthermore, multiple logistic regression analysis indicated that daily urine output on the second day of ECMO removal (UO_{24–48 hour}), mean arterial pressure (MAP), and SOFA score on the day of ECMO removal were independent predictors of hospital mortality. Finally, cumulative survival rates at 6-month follow-up differed significantly (p<0.001) for a SOFA score≤13 relative to those for a SOFA score>13.

Conclusions

Following successful ECMO weaning, the SOFA score proved a reproducible evaluation tool with good prognostic abilities.     

Psychiatric Comorbidity and Its Impact on Mortality in Patients Who Attempted Suicide by Paraquat Poisoning during 2000–2010

Background

Paraquat poisoning is a lethal method of suicide used around the world. Although restricting its accessibility had been widely discussed, the underlying psychopathological mechanism of paraquat self-poisoning and its association with mortality have not yet been explicitly evaluated.

Methods

We included all patients admitted to a tertiary general hospital in Taiwan between 2000 and 2010 following a suicide attempt by paraquat self-administration. Diagnoses were made upon psychiatric consultation based on the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria. The risk of mortality was calculated by logistic regression with various psychiatric or medical covariates.

Results

The consultation-liaison psychiatry team assessed 157 patients who attempted suicide by paraquat poisoning. Mood disorders (54.0%), including dysthymic (26.7%) and major depressive disorders (24.7%), were the most common psychiatric diagnoses among the self-poisoning patients. Among those who attempted suicide, 87 patients (58.0%) died and dysthymic disorder (OR = 5.58, 95% CI: 1.13–27.69; p<0.05) significantly increased the mortality risk after adjustment for relevant medical variables, including age, gender, severity index of paraquat poisoning (SIPP), and risk for respiratory failure.

Conclusions

Awareness of comorbid psychiatric illnesses, especially dysthymic disorder, is vital in the prevention and treatment of suicide by paraquat poisoning.     

Acute Kidney Injury Enhances Outcome Prediction Ability of Sequential Organ Failure Assessment Score in Critically Ill Patients

Introduction

Acute kidney injury (AKI) is a common and serious complication in intensive care unit (ICU) patients and also often part of a multiple organ failure syndrome. The sequential organ failure assessment (SOFA) score is an excellent tool for assessing the extent of organ dysfunction in critically ill patients. This study aimed to evaluate the outcome prediction ability of SOFA and Acute Physiology and Chronic Health Evaluation (APACHE) III score in ICU patients with AKI.

Methods

A total of 543 critically ill patients were admitted to the medical ICU of a tertiary-care hospital from July 2007 to June 2008. Demographic, clinical and laboratory variables were prospectively recorded for post hoc analysis as predictors of survival on the first day of ICU admission.

Results

One hundred and eighty-seven (34.4%) patients presented with AKI on the first day of ICU admission based on the risk of renal failure, injury to kidney, failure of kidney function, loss of kidney function, and end-stage renal failure (RIFLE) classification. Major causes of the ICU admissions involved respiratory failure (58%). Overall in-ICU mortality was 37.9% and the hospital mortality was 44.7%. The predictive accuracy for ICU mortality of SOFA (areas under the receiver operating characteristic curves: 0.815±0.032) was as good as APACHE III in the AKI group. However, cumulative survival rates at 6-month follow-up following hospital discharge differed significantly (p<0.001) for SOFA score ≤10 vs. ≥11 in these ICU patients with AKI.

Conclusions

For patients coexisting with AKI admitted to ICU, this work recommends application of SOFA by physicians to assess ICU mortality because of its practicality and low cost. A SOFA score of ≥ “11” on ICU day 1 should be considered an indicator of negative short-term outcome.     

Association of Radiologic Findings with Mortality in Patients with Avian Influenza H7N9 Pneumonia

Background

The novel H7N9 virus causes severe illness, including pneumonia and acute respiratory distress syndrome, with high rates of mortality. We investigated the association of initial radiologic characteristics obtained at admission with clinical outcomes in patients with avian influenza H7N9 pneumonia.

Methods

Demographics, comorbidities, clinical findings, radiologic appearance and scores of the affected lung parenchyma were compared between survivor group (n = 15) and mortality group (n = 7). Two radiologic scores were calculated, one using chest radiography and one using CT. Follow-up CT scans at discharge were analyzed in 12 patients of the survival group.

Results

All the patients in mortality group developed acute respiratory distress syndrome and required mechanical ventilation, while in the survival group 33% (5/15) developed acute respiratory distress syndrome (P<0.05) and 27% (4/15) required mechanical ventilation (P<0.05). The mean radiographic and CT scores of the mortality group were 50% higher compared to the survival group (P<0.05). ROC analysis revealed an area under curve of 0.738 for the radiographic score with an optimal cutoff value of a score of 19 for prediction of mortality, with a sensitivity of 71% and a specificity of 67%, and an area under curve of 0.833 for the CT score with an optimal cutoff value of a CT score of 21 for prediction of mortality, with a sensitivity of 86% and a specificity of 73%. The mean CT score of the affected lung parenchyma at discharge was 30% lower than the initial CT examination (P<0.05).

Conclusion

High initial radiologic score is associated with mortality in patients with avian influenza H7N9 pneumonia.     

Serum Levels of Caspase-Cleaved Cytokeratin-18 and Mortality Are Associated in Severe Septic Patients: Pilot Study

Objective

Apoptosis is increased in sepsis. Cytokeratin 18 (CK-18), a protein of the intermediate filament group present in most epithelial and parenchymal cells, is cleaved by the action of caspases and released into the blood as caspase-cleaved CK (CCCK)-18 during apoptosis. Circulating levels of CCCK-18 have scarcely been explored in septic patients. In one study with 101 severe septic patients, the authors reported higher serum CCCK-18 levels in non-survivors than in survivors; however, the sample size was too small to demonstrate an association between serum CCCK-18 levels and early mortality and whether they could be used as a biomarker to predict outcomes in septic patients. Thus, these were the objectives of this study with a large series of patients.

Methods

We performed a prospective, multicenter, observational study in six Spanish Intensive Care Units with 224 severe septic patients. Blood samples were collected at the time that severe sepsis was diagnosed to determine serum levels of CCCK-18, tumor necrosis factor (TNF)-alpha, interleukin (IL)-6 and IL-10. The end point was 30-day mortality.

Results

Non-surviving patients (n = 80) showed higher serum CCCK-18 levels (P<0.001) than survivors (n = 144). Multiple logistic regression analysis showed that serum CCCK-18 levels>391 u/L were associated with 30-day survival (Odds ratio = 2.687; 95% confidence interval = 1.449–4.983; P = 0.002), controlling for SOFA score, serum lactic acid levels and age. Kaplan-Meier survival analysis showed that the risk of death in septic patients with serum CCCK-18 levels >391 u/L was higher than in patients with lower values (Hazard Ratio = 3.1; 95% CI = 1.96–4.84; P<0.001). Serum CCCK-18 levels were positively associated with serum levels of IL-6 and lactic acid, and with SOFA and APACHE scores.

Conclusions

The major novel finding of our study, the largest cohort of septic patients providing data on circulating CCCK-18 levels, was that serum CCCK-18 levels are associated with mortality in severe septic patients.     

Absolute Lymphocyte Count as a Predictor of Mortality in Emergency Department Patients with Paraquat Poisoning

Background

Paraquat (PQ) is a potent, highly toxic and widely used herbicide. The major medical problems associated with PQ are accidental or suicidal ingestion. There are several prognostic markers of PQ poisoning, with the serum PQ concentration considered to be the best indicator of outcome. However, the measurement of such markers is limited in many hospitals.

Objective

The present study was conducted to investigate the association of absolute lymphocyte count (ALC) and the 30-day mortality rate in patients with PQ poisoning.

Methods

We performed a retrospective analysis of patients admitted to the emergency department after paraquat poisoning between January 2010 and April 2013. Independent risk factors including ALC for 30-day mortality were determined. The ALC was categorized in quartiles as ≤1700, 1700 to 3200, 3200 to 5000, and >5000. Univariate and multivariate Cox proportional hazard analysis were performed to determine the independent risk factors for mortality.

Results

A total of 136 patients were included in the study, and the 30-day mortality was 73.5%. ALC was significantly higher in nonsurvivors than in survivors. The highest ALC quartile (ALC>5000; hazard ratio, 2.58; 95% CI, 1.08–6.21) was associated with increased mortality in multivariate analysis. In addition, old age, lower arterial PaCO₂, increased peripheral neutrophil count, and high serum levels of creatinine were associated with mortality.

Conclusion

The absolute lymphocyte count is associated with the 30-day mortality rate in patients with paraquat poisoning.     

Use of CHADS2 and CHA2DS2-VASc Scores to Predict Subsequent Myocardial Infarction,Stroke, and Death in Patients with Acute Coronary Syndrome: Data from Taiwan Acute Coronary Syndrome Full Spectrum Registry

Background

Acute coronary syndrome (ACS) patients have a wide spectrum of risks for subsequent cardiovascular events and death. However, there is no simple, convenience scoring system to identify risk of adverse outcomes. We investigated whether CHADS₂ and CHA₂DS₂-VASc scores were useful tools to assess the risk for adverse events among ACS patients.

Methods

This observational prospective study was conducted at 39 hospitals. Totally 3,183 patients with ACS were enrolled, and CHADS₂ and CHA₂DS₂-VASc scores were calculated. The primary endpoint was occurrence of adverse event, including subsequent myocardial infarction, stroke, or death, within 1 year of discharge.

Results

CHADS₂ and CHA₂DS₂-VASc scores were significant predictors of adverse events in separate multivariate regression analyses. A Kaplan-Meier analysis of CHADS₂ and CHA₂DS₂-VASc scores of ≥2 showed a higher rate of adverse events as compared with scores of <2 (P<0.001;log-rank test). CHA₂DS₂-VASc score was better than CHADS₂ score in predicting subsequent adverse events; the area under the receiver operating characteristic curve increased from 0.66 to 0.70 (p<0.001). Patients with CHADS₂ scores of 0 or 1 were further classified according to CHA₂DS₂-VASc score, using a cutoff value of 2. The rate of adverse events significantly differed between those with a score of <2 and those with a score of ≥2 (4.1% vs.10.7%, P<0.001).

Conclusions

CHADS₂ and CHA₂DS₂-VASc scores were useful predictors of subsequent adverse events in ACS patients.     

Red Blood Cell Distribution Width during the First Week Is Associated with Severity and Mortality in Septic Patients

Objective

Higher values of red blood cell distribution width (RDW) have been found in non-surviving than in surviving septic patients. However, it is unknown whether RDW during the first week of sepsis evolution is associated with sepsis severity and early mortality, oxidative stress and inflammation states, and these were the aims of the study.

Methods

We performed a prospective, observational, multicenter study in six Spanish Intensive Care Units with 297 severe septic patients. We measured RDW, serum levels of malondialdehyde (MDA) to assess oxidative stress, and tumour necrosis factor (TNF)-α to assess inflammation at days 1, 4, and 8. The end-point was 30-day mortality.

Results

We found higher RDW in non-surviving (n = 104) than in surviving (n = 193) septic patients at day 1 (p = 0.001), day 4 (p = 0.001), and day 8 (p = 0.002) of ICU admission. Cox regression analyses showed that RDW at day 1 (p<0.001), 4 (p = 0.005) and 8 (p = 0.03) were associated with 30-day mortality. Receiver operating characteristic curves showed that RDW at day 1 (p<0.001), 4 (p<0.001), and 8 (p<0.001) could be used to predict 30-day mortality. RDW showed a positive correlation with serum MDA levels at day 1 and day 4, with serum TNF-α levels at days 4 and 8, and with SOFA score at days 1, 4 and 8.

Conclusions

The major findings of our study were that non-surviving septic patients showed persistently higher RDW during the first week of ICU stay than survivors, that RDW during the first week was associated with sepsis severity and mortality, that RDW during the first week could be used as biomarker of outcome in septic patients, and that there was an association between RDW, serum MDA levels, and serum TNF-α levels during the first week.     

Severity Assessment of Lower Respiratory Tract Infection in Malawi: Derivation of a Novel Index (SWAT-Bp) Which Outperforms CRB-65

Objective

To assess the validity of CRB-65 (Confusion, Respiratory rate >30 breaths/min, BP<90/60 mmHg, age >65 years) as a pneumonia severity index in a Malawian hospital population, and determine whether an alternative score has greater accuracy in this setting.

Design

Forty three variables were prospectively recorded during the first 48 hours of admission in all patients admitted to Queen Elizabeth Central Hospital, Malawi, for management of lower respiratory tract infection over a two month period (N = 240). Calculation of sensitivity and specificity for CRB-65 in predicting mortality was followed by multivariate modeling to create a score with superior performance in this population.

Results

Median age 37, HIV prevalence 79.9%, overall mortality 18.3%. CRB-65 predicted mortality poorly, indicated by the area under the ROC curve of 0.649. Independent predictors of death were: Male sex, “S” (AOR 2.6); Wasting, “W” (AOR 6.6); non-ambulatory, “A” (AOR 2.5); Temp >38°C or <35°C, “T” (AOR 3.2); BP<100/60, “Bp” (AOR 3.7). Combining these factors to form a severity index (SWAT-Bp) predicted mortality with high sensitivity and specificity (AUC: 0.867). Mortality for scores 0–5 was 0%, 3.3%, 7.4%, 29.2%, 61.5% and 87.5% respectively. A score ≥3 was 84% sensitive and 77% specific for mortality prediction, with a negative predictive value of 95.8%.

Conclusion

CRB-65 performs poorly in this population. The SWAT-Bp score can accurately stratify patients; ≤2 indicates non-severe infection (mortality 4.4%) and ≥3 severe illness (mortality 45%).     

The Volume Ratio of Ground Glass Opacity in Early Lung CT Predicts Mortality in Acute Paraquat Poisoning

Background

Pulmonary injury is the main cause of death in acute paraquat (PQ) poisoning. However, whether quantitative lung computed tomography (CT) can be useful in predicting the outcome of PQ poisoning remains unknown. We aimed to identify early findings of quantitative lung CT as predictors of outcome in acute PQ poisoning.

Methods

Lung CT scanning (64-slide) and quantitative CT lesions were prospectively measured for patients after PQ intoxication within 5 days. The study outcome was mortality during 90 days follow-up. Survival curves were derived by the Kaplan-Meier method, and mortality risk factors were analyzed by the forward stepwise Cox regression analysis.

Results

Of 97 patients, 41 (42.3%) died. Among the eight different types of lung CT findings which appeared in the first 5-day of PQ intoxication, four ones discriminated between survivors and non-survivors including ground glass opacity (GGO), consolidation, pneumomediastinum and “no obvious lesion”. With a cutoff value of 10.8%, sensitivity of 85.4% and specificity of 89.3%, GGO volume ratio is better than adopted outcome indicators in predicting mortality, such as estimated amount of PQ ingestion, plasma or urine PQ concentration, acute physiology and chronic health evaluation (APACHE) II and sequential organ failure assessment (SOFA) scores. GGO volume ratios above 10.8% were associated with increased mortality (hazard ratio, 5.82; 95% confidence interval, 4.77-7.09; P < 0.001).

Conclusions

The volume ratio of GGO exceeding 10.8% is a novel, reliable and independent predictors of outcome in acute PQ poisoning.     

Early Hemoperfusion May Improve Survival of Severely Paraquat-Poisoned Patients

Background

Thousands of paraquat (PQ)-poisoned patients continue to die, particularly in developing countries. Although animal studies indicate that hemoperfusion (HP) within 2−4 h after intoxication effectively reduces mortality, the effect of early HP in humans remains unknown.

Methods

We analyzed the records of all PQ-poisoned patients admitted to 2 hospitals between 2000 and 2009. Patients were grouped according to early or late HP and high-dose (oral cyclophosphamide [CP] and intravenous dexamethasone [DX]) or repeated pulse (intravenous methylprednisolone [MP] and CP, followed by DX and repeated MP and/or CP) PQ therapy. Early HP was defined as HP <4 h, and late HP, as HP ≥4 h after PQ ingestion. We evaluated the associations between HP <4 h, <5 h, <6 h, and <7 h after PQ ingestion and the outcomes. Demographic, clinical, laboratory, and mortality data were analyzed.

Results

The study included 207 severely PQ-poisoned patients. Forward stepwise multivariate Cox hazard regression analysis showed that early HP <4 h (hazard ratio [HR] = 0.38, 95% confidence interval (CI) 0.16–0.86; P = 0.020) or HP <5 h (HR = 0.60, 95% CI: 0.39–0.92; P = 0.019) significantly decreased the mortality risk. Further analysis showed that early HP reduced the mortality risk only in patients treated with repeated pulse therapy (n = 136), but not high-dose therapy (n = 71). Forward stepwise multivariate Cox hazard regression analysis showed that HP <4.0 h (HR = 0.19, 95% CI: 0.05–0.79; P = 0.022) or <5.0 h (HR = 0.49, 95% CI: 0.24–0.98; P = 0.043) after PQ ingestion significantly decreased the mortality risk in repeated pulse therapy patients, after adjustment for relevant variables.

Conclusion

The results showed that early HP after PQ exposure might be effective in reducing mortality in severely poisoned patients, particularly in those treated with repeated pulse therapy.     

Serum Procalcitonin Level and SOFA Score at Discharge from the Intensive Care Unit Predict Post-Intensive Care Unit Mortality: A Prospective Study

Purpose

The final decision for discharge from the intensive care unit (ICU) is uncertain because it is made according to various patient parameters; however, it should be made on an objective evaluation. Previous reports have been inconsistent and unreliable in predicting post-ICU mortality. To identify predictive factors associated with post-ICU mortality, we analyzed physiological and laboratory data at ICU discharge.

Methods

Patients admitted to our ICU between September 2012 and August 2013 and staying for critical care>2 days were included. Sequential Organ Failure Assessment (SOFA) score; systemic inflammatory response syndrome score; white blood cell count; and serum C reactive protein, procalcitonin (PCT), interleukin-6 (IL-6), lactate, albumin, and hemoglobin levels were recorded. The primary end point was 90-day mortality after ICU discharge. Two hundred eighteen patients were enrolled (195 survivors, 23 non-survivors).

Results

Non-survivors presented a higher SOFA score and serum PCT, and IL-6 levels, as well as lower serum albumin and hemoglobin levels. Serum PCT, albumin, and SOFA score were associated with 90-day mortality in multiple logistic regression analysis. Hosmer-Lemeshow test showed chi-square value of 6.96, and P value of 0.54. The area under the curve (95% confidence interval) was 0.830 (0.771–0.890) for PCT, 0.688 (0.566–0.810) for albumin, 0.861 (0.796–0.927) for SOFA score, and increased to 0.913 (0.858–0.969) when these were combined. Serum PCT level at 0.57 ng/mL, serum albumin at 2.5 g/dL and SOFA score at 5.5 predict 90-day mortality, and high PCT, low albumin and high SOFA groups had significantly higher mortality. Serum PCT and SOFA score were significantly associated with survival days after ICU discharge in Cox regression analysis.

Conclusions

Serum PCT level and SOFA score at ICU discharge predict post-ICU mortality and survival days after ICU discharge. The combination of these two and albumin level might enable accurate prediction.     

Hematoma Shape,Hematoma Size,Glasgow Coma Scale Score and ICH Score: Which Predicts the 30-Day Mortality Better for Intracerebral Hematoma?

Purpose

To investigate the performance of hematoma shape, hematoma size, Glasgow coma scale (GCS) score, and intracerebral hematoma (ICH) score in predicting the 30-day mortality for ICH patients. To examine the influence of the estimation error of hematoma size on the prediction of 30-day mortality.

Materials and Methods

This retrospective study, approved by a local institutional review board with written informed consent waived, recruited 106 patients diagnosed as ICH by non-enhanced computed tomography study. The hemorrhagic shape, hematoma size measured by computer-assisted volumetric analysis (CAVA) and estimated by ABC/2 formula, ICH score and GCS score was examined. The predicting performance of 30-day mortality of the aforementioned variables was evaluated. Statistical analysis was performed using Kolmogorov-Smirnov tests, paired t test, nonparametric test, linear regression analysis, and binary logistic regression. The receiver operating characteristics curves were plotted and areas under curve (AUC) were calculated for 30-day mortality. A P value less than 0.05 was considered as statistically significant.

Results

The overall 30-day mortality rate was 15.1% of ICH patients. The hematoma shape, hematoma size, ICH score, and GCS score all significantly predict the 30-day mortality for ICH patients, with an AUC of 0.692 (P = 0.0018), 0.715 (P = 0.0008) (by ABC/2) to 0.738 (P = 0.0002) (by CAVA), 0.877 (P<0.0001) (by ABC/2) to 0.882 (P<0.0001) (by CAVA), and 0.912 (P<0.0001), respectively.

Conclusion

Our study shows that hematoma shape, hematoma size, ICH scores and GCS score all significantly predict the 30-day mortality in an increasing order of AUC. The effect of overestimation of hematoma size by ABC/2 formula in predicting the 30-day mortality could be remedied by using ICH score.     

Dickkopf-1 as a Novel Predictor Is Associated with Risk Stratification by GRACE Risk Scores for Predictive Value in Patients with Acute Coronary Syndrome: A Retrospective Research

Objective

Dickkopf-1 (DKK-1), a major regulator of the Wnt pathway, plays an important role in cardiovascular disease. However, no study has evaluated the association of DKK-1 and acute coronary syndrome (ACS). We investigated this association and whether the Global Registry of Acute Coronary Events (GRACE) hospital-discharge risk score predicting major adverse cardiac events (MACE) can be improved by adding the DKK-1 value.

Methods

We enrolled 291 patients (46 with ST-segment elevation myocardial infarction [STEMI] and 245 with non-ST elevated ACS [NSTE-ACS]) who were divided into groups by tertiles of baseline plasma DKK-1 level measured by ELISA. The GRACE risk score was calculated and predictive value alone and together with DKK-1 and/or high-sensitivity C-reactive protein (hs-CRP) level were assessed, respectively.

Results

Compared with patients with NSTE-ACS, those with STEMI had higher plasma DKK-1 level at baseline (P = 0.006). Plasma DKK-1 level was correlated with hs-CRP level (r = 0.295, P<0.001) and was greater with high than intermediate or low GRACE scores (P = 0.002 and P<0.001, respectively). We found 44 (15.1%) MACEs during a median 2-year follow-up. DKK-1 levels were higher for patients with than without events (P<0.001). The rate of MACE increased with increasing DKK-1 level (P<0.001). The area under the receiver operating characteristic curve for GRACE score with MACE was 0.524 and improved to 0.791 with the addition of hs-CRP level, 0.775 with the addition of DKK-1 level and 0.847 with both values added.

Conclusions

DKK-1 is an independent predictor of long-term MACE of patients with ACS. The long-term predictive ability of post-discharge GRACE score may be enhanced by adding DKK-1 level.     

Biomarkers of Endothelial Activation Are Associated with Poor Outcome in Critical Illness

Background

Endothelial activation plays a role in organ dysfunction in the systemic inflammatory response syndrome (SIRS). Angiopoietin-1 (Ang-1) promotes vascular quiescence while angiopoietin-2 (Ang-2) mediates microvascular leak. Circulating levels of Ang-1 and Ang-2 in patients with SIRS could provide insight on risks for organ dysfunction and death distinct from inflammatory proteins. In this study, we determined if biomarkers of endothelial activation and inflammation exhibit independent associations with poor outcomes in SIRS.

Methods

We studied 943 critically ill patients with SIRS admitted to an Intensive Care Unit (ICU) of an academic medical center. We measured plasma levels of endothelial markers (Ang-1, Ang-2, soluble vascular cell adhesion molecule-1 (sVCAM-1)) and inflammatory markers (interleukin-6 (IL-6), interleukin-8 (IL-8), granulocyte-colony stimulating factor (G-CSF), soluble tumor necrosis factor receptor-1 (sTNFR-1)) within 24 hours of enrollment. We tested for associations between each marker and 28 day mortality, shock, and day 3 sequential organ failure assessment (SOFA) score. For 28 day mortality, we performed sensitivity analysis for those subjects with sepsis and those with sterile inflammation. We used multivariate models to adjust for clinical covariates and determine if associations identified with endothelial activation markers were independent of those observed with inflammatory markers.

Results

Higher levels of all biomarkers were associated with increased 28 day mortality except levels of Ang-1 which were associated with lower mortality. After adjustment for comorbidities and sTNFR-1 concentration, a doubling of Ang-1 concentration was associated with lower 28 day mortality (Odds ratio (OR) = 0.81; p<0.01), shock (OR = 0.82; p<0.001), and SOFA score (β = -0.50; p<0.001), while Ang-2 concentration was associated with increased mortality (OR = 1.55; p<0.001), shock (OR = 1.51; p<0.001), and SOFA score (β = +0.63; p<0.001). sVCAM-1 was not independently associated with SIRS outcomes.

Conclusions

In critically ill patients with SIRS, early measurements of Ang-1 and Ang-2 are associated with death and organ dysfunction independently of simultaneously-measured markers of inflammation.     

Effect of Sodium Bicarbonate Administration on Mortality in Patients with Lactic Acidosis: A Retrospective Analysis

Background

Lactic acidosis is a common cause of high anion gap metabolic acidosis. Sodium bicarbonate may be considered for an arterial pH <7.15 but paradoxically depresses cardiac performance and exacerbates acidosis by enhancing lactate production. This study aimed to evaluate the cause and mortality rate of lactic acidosis and to investigate the effect of factors, including sodium bicarbonate use, on death.

Methods

We conducted a single center analysis from May 2011 through April 2012. We retrospectively analyzed 103 patients with lactic acidosis among 207 patients with metabolic acidosis. We used SOFA and APACHE II as severity scores to estimate illness severity. Multivariate logistic regression analysis and Cox regression analysis models were used to identify factors that affect mortality.

Results

Of the 103 patients with a mean age of 66.1±11.4 years, eighty-three patients (80.6%) died from sepsis (61.4%), hepatic failure, cardiogenic shock and other causes. The percentage of sodium bicarbonate administration (p = 0.006), catecholamine use, ventilator care and male gender were higher in the non-survival group than the survival group. The non-survival group had significantly higher initial and follow-up lactic acid levels, lower initial albumin, higher SOFA scores and APACHE II scores than the survival group. The mortality rate was significantly higher in patients who received sodium bicarbonate. Sodium bicarbonate administration (p = 0.016) was associated with higher mortality. Independent factors that affected mortality were SOFA score (Exp (B) = 1.72, 95% CI = 1.12–2.63, p = 0.013) and sodium bicarbonate administration (Exp (B) = 6.27, 95% CI = 1.10–35.78, p = 0.039).

Conclusions

Lactic acidosis, which has a high mortality rate, should be evaluated in patients with metabolic acidosis. In addition, sodium bicarbonate should be prescribed with caution in the case of lactic acidosis because sodium bicarbonate administration may affect mortality.     

Pretransplant prediction of posttransplant survival for liver recipients with benign end-stage liver diseases: a nonlinear model

Background

The scarcity of grafts available necessitates a system that considers expected posttransplant survival, in addition to pretransplant mortality as estimated by the MELD. So far, however, conventional linear techniques have failed to achieve sufficient accuracy in posttransplant outcome prediction. In this study, we aim to develop a pretransplant predictive model for liver recipients'' survival with benign end-stage liver diseases (BESLD) by a nonlinear method based on pretransplant characteristics, and compare its performance with a BESLD-specific prognostic model (MELD) and a general-illness severity model (the sequential organ failure assessment score, or SOFA score).

Methodology/Principal Findings

With retrospectively collected data on 360 recipients receiving deceased-donor transplantation for BESLD between February 1999 and August 2009 in the west China hospital of Sichuan university, we developed a multi-layer perceptron (MLP) network to predict one-year and two-year survival probability after transplantation. The performances of the MLP, SOFA, and MELD were assessed by measuring both calibration ability and discriminative power, with Hosmer-Lemeshow test and receiver operating characteristic analysis, respectively. By the forward stepwise selection, donor age and BMI; serum concentration of HB, Crea, ALB, TB, ALT, INR, Na⁺; presence of pretransplant diabetes; dialysis prior to transplantation, and microbiologically proven sepsis were identified to be the optimal input features. The MLP, employing 18 input neurons and 12 hidden neurons, yielded high predictive accuracy, with c-statistic of 0.91 (P<0.001) in one-year and 0.88 (P<0.001) in two-year prediction. The performances of SOFA and MELD were fairly poor in prognostic assessment, with c-statistics of 0.70 and 0.66, respectively, in one-year prediction, and 0.67 and 0.65 in two-year prediction.

Conclusions/Significance

The posttransplant prognosis is a multidimensional nonlinear problem, and the MLP can achieve significantly high accuracy than SOFA and MELD scores in posttransplant survival prediction. The pattern recognition methodologies like MLP hold promise for solving posttransplant outcome prediction.     

Predisposition,Insult/Infection,Response and Organ Dysfunction (PIRO): A Pilot Clinical Staging System for Hospital Mortality in Patients with Infection

Purpose

To develop a clinical staging system based on the PIRO concept (Predisposition, Infection, Response and Organ dysfunction) for hospitalized patients with infection.

Methods

One year prospective cohort study of all hospitalized patients with infection (n = 1035), admitted into a large tertiary care, university hospital. Variables associated with hospital mortality were selected using logistic regressions. Based on the regression coefficients, a score for each PIRO component was developed and a classification tree was used to stratify patients into four stages of increased risk of hospital mortality. The final clinical staging system was then validated using an independent cohort (n = 186).

Results

Factors significantly associated with hospital mortality were • for Predisposition: age, sex, previous antibiotic therapy, chronic hepatic disease, chronic hematologic disease, cancer, atherosclerosis and a Karnofsky index<70; • for Insult/Infection: type of infection • for Response: abnormal temperature, tachypnea, hyperglycemia and severity of infection and • for Organ dysfunction: hypotension and SOFA score≥1. The area under the ROC curve (CI_95%) for the combined PIRO model as a predictor for mortality was 0.85 (0.82–0.88). Based on the scores for each of the PIRO components and on the cut-offs estimated from the classification tree, patients were stratified into four stages of increased mortality rates: stage I: ≤5%, stage II: 6–20%, stage III: 21–50% and stage IV: >50%. Finally, this new clinical staging system was studied in a validation cohort, which provided similar results (0%, 9%, 31% and 67%, in each stage, respectively).

Conclusions

Based on the PIRO concept, a new clinical staging system was developed for hospitalized patients with infection, allowing stratification into four stages of increased mortality, using the different scores obtained in Predisposition, Response, Infection and Organ dysfunction. The proposed system will likely help to define inclusion criteria in clinical trials as well as tailoring individual management plans for patients with infection.     

Mortality Patterns and Site Heterogeneity of Severe Malaria in African Children

Background

In this study we aimed to assess site heterogeneity of early, intermediate, and late mortality prediction in children with severe Plasmodium falciparum malaria in sub-Saharan Africa.

Methods

Medical records of 26,036 children admitted with severe Plasmodium falciparum malaria in six hospital research centers between December 2000 to May 2005 were analyzed. Demographic, clinical and laboratory data of children who died within 24 hours (early), between 24 and 47 hours (intermediate) and thereafter (48 hours or later, late mortality) were compared between groups and survivors.

Results

Overall mortality was 4·3% (N = 1,129). Median time to death varied across sites (P<0·001), ranging from 8h (3h–52h) in Lambaréné to 40h (10h–100h) in Kilifi. Fifty-eight percent of deaths occurred within 24 hours and intermediate and late mortality rate were 19% and 23%, respectively. Combining all sites, deep breathing, prostration and hypoglycemia were independent predictors for early, intermediate and late mortality (P<0·01). Site specific independent predictors for early death included prostration, coma and deep breathing at all sites (P<0·001). Site specific independent predictors for intermediate and late death largely varied between sites (P<0·001) and included between 1 and 7 different clinical and laboratory variables.

Conclusion

Site heterogeneity for mortality prediction is evident in African children with severe malaria. Prediction for early mortality has the highest consistency between sites.