A retrospective analysis reveals a predictor of survival for the patient with paraquat intoxication.

Feasible and accurate predictors are urgently needed to evaluate the survival for patients with paraquat poisoning since the high mortality of paraquat poisoning always resulted in the loss of both life and money. Multiple predictors have been developed to predict prognosis of the patients with PQ poisoning, which however heavily depend on the time of admission to hospitals. Here we reported a feasible and accurate prognosis predictor for patients with paraquat poisoning that is independent of the time of admission to hospitals. Patients with paraquat poisoning were enrolled in this study according to the inclusion and exclusion criteria, which were grouped into survivors and non-survivors based on the 90-days follow-up investigation. The concentration of paraquat in serum and urine, and the baseline clinical parameters associated with the injuries of the liver, kidney, and lung were evaluated to predict the survival of these patients by using receiver operating characteristic curve (ROC) analysis, univariate and multivariate cox regression analyses. A total of 114 patients was included in this study with a survival rate of 54.4%. The median survival days of non-survivors were 6.0 (95%Cl: 4.0-7.8). A new predictor, namely paraquat concentration-associated multiorgan injury index (PCAMII), was established by integrating serum and urine paraquat concentration, serum creatinine, alanine aminotransferase, aspartate transaminase, total and direct bilirubin, at different weighting coefficients, with the accuracy of about 90%. The model to predict the survival probability by PCAMII was established with good fitness (R2 = 0.9325), providing the simulated survival rates comparable to the clinical data. PCAMII, which is independent of hospital admission time, is a feasible and accurate marker to predict the survival rate of patients with PQ poisoning.

Oxylipin profiling of human plasma reflects the renal dysfunction in uremic patients.

INTRODUCTION: Nearly all the enzymes that mediate the metabolism of polyunsaturated fatty acids (PUFAs) are present in the kidney. However, the correlation of renal dysfunction with PUFAs metabolism in uremic patients remains unknown. OBJECTIVES: To test whether the alterations in the metabolism of PUFAs reflect the renal dysfunction in uremic patients. METHODS: LC-MS/MS-based oxylipin profiling was conducted for the plasma samples from the uremic patients and controls. The data were analyzed by principal component analysis (PCA) and orthogonal partial least squares-discriminant analysis (OPLS-DA). The receiver operating characteristic (ROC) curves and the correlation of the estimated glomerular filtration rate (eGFR) with the key markers were evaluated. Furthermore, qPCR analysis of the whole blood cells was conducted to investigate the possible mechanisms. In addition, a 2nd cohort was used to validate the findings from the 1st cohort. RESULTS: The plasma oxylipin profile distinguished the uremic patients from the controls successfully by using both PCA and OPLS-DA models. 5,6-Dihydroxyeicosatrienoic acid (5,6-DHET), 5-hydroxyeicosatetraenoic acid (5-HETE), 9(10)-epoxyoctadecamonoenoic acid [9(10)-EpOME] and 12(13)-EpOME were identified as the key markers to discriminate the patients from controls. The excellent predictive performance of these four markers was validated by ROC analysis. The eGFR significantly correlated with plasma levels of 5,6-DHET and 5-HETE positively but with plasma 9(10)-EpOME and 12(13)-EpOME negatively. The changes of these markers may account for the inactivation of cytochrome P450 2C18, 2C19, microsome epoxide hydrolase (EPHX1), and 5-lipoxygenase in the patients. CONCLUSION: The alterations in plasma metabolic profile reflect the renal dysfunction in the uremic patients.

Epoxide metabolites of arachidonate and docosahexaenoate function conversely in acute kidney injury involved in GSK3ß signaling.

Acute kidney injury (AKI) causes severe morbidity and mortality for which new therapeutic strategies are needed. Docosahexaenoic acid (DHA), arachidonic acid (ARA), and their metabolites have various effects in kidney injury, but their molecular mechanisms are largely unknown. Here, we report that 14 (15)-epoxyeicosatrienoic acid [14 (15)-EET] and 19 (20)-epoxydocosapentaenoic acid [19 (20)-EDP], the major epoxide metabolites of ARA and DHA, respectively, have contradictory effects on kidney injury in a murine model of ischemia/reperfusion (I/R)-caused AKI. Specifically, 14 (15)-EET mitigated while 19 (20)-EDP exacerbated I/R kidney injury. Manipulation of the endogenous 19 (20)-EDP or 14 (15)-EET by alteration of their degradation or biosynthesis with selective inhibitors resulted in anticipated effects. These observations are supported by renal histological analysis, plasma levels of creatinine and urea nitrogen, and renal NGAL. The 14 (15)-EET significantly reversed the I/R-caused reduction in glycogen synthase kinase 3ß (GSK3ß) phosphorylation in murine kidney, dose-dependently inhibited the hypoxia/reoxygenation (H/R)-caused apoptosis of murine renal tubular epithelial cells (mRTECs), and reversed the H/R-caused reduction in GSK3ß phosphorylation in mRTECs. In contrast, 19 (20)-EDP dose-dependently promoted H/R-caused apoptosis and worsened the reduction in GSK3ß phosphorylation in mRTECs. In addition, 19 (20)-EDP was more metabolically stable than 14 (15)-EET in vivo and in vitro. Overall, these epoxide metabolites of ARA and DHA function conversely in I/R-AKI, possibly through their largely different metabolic stability and their opposite effects in modulation of H/R-caused RTEC apoptosis and GSK3ß phosphorylation. This study provides AKI patients with promising therapeutic strategies and clinical cautions.

N-acetylcysteine for the prevention of contrast-induced nephropathy in patients with pre-existing renal insufficiency or diabetes: a systematic review and meta-analysis.

PURPOSE: To identify benefit of N-acetylcysteine (NAC) on patients with pre-existing renal insufficiency or diabetes. BACKGROUND: NAC administration is a common method for prevention of contrast-induced nephropathy (CIN). Nevertheless, its benefit on patients with pre-existing renal insufficiency or diabetes remains uncertain and controversial. METHODS: Randomized controlled trials (RCTs) to evaluate the efficacy of NAC for the prevention of CIN in patients with pre-existing renal insufficiency or diabetes were searched from the databases of MEDLINE, EMBASE, and Cochrane library. Pooled odds ratio (OR) with 95% confidence interval (95% CI) were calculated using fixed-effects model by the Mantel-Haenszel test. RESULTS: Twenty RCTs involving 3466 subjects (1756 assigned to NAC and 1710 assigned to the control) were included in the pre-existing renal dysfunction group. Pooled analysis suggested a significant reduction in CIN among this group (OR, 0.76; 95% CI, 0.61-0.93; p = 0.008). However, the nine trials comparing NAC versus control among patients with diabetes (NAC, 367 subjects; control, 358 subjects) showed no benefit of NAC for prevention of CIN (OR = 0.87; 95% CI, 0.58-1.30; p = 0.50). No significant heterogeneity was detected (p = 0.07; I2 = 34% for the group of pre-existing renal dysfunction; p = 0.40; I2 = 5% for the group of diabetes). CONCLUSION: Our results suggest that NAC decreases the incidence of contrast-induced nephropathy among patients with pre-existing renal insufficiency. The benefit was not existed in patients with diabetes.

Pneumomediastinum predicts early mortality in acute paraquat poisoning.

CONTEXT: In paraquat (PQ) poisoning, death often occurs after the appearance of pneumomediastinum (PM). However, the clinical features and eventual outcome of PM in PQ intoxication remains unclear. OBJECTIVE: We aimed to characterize PM following PQ poisoning and its prognostic value for predicting mortality. MATERIALS AND METHODS: Enrolled PQ-poisoned patients (n = 75) were divided into two groups according to whether PM could be detected by chest computed tomography or not. The study outcomes included 5- and 90-day death after intoxication. Survival curves were derived using the Kaplan-Meier method, and mortality risk factors were analyzed by forward stepwise Cox regression analysis. RESULTS: PM was documented in 21.3% of the patients (16/75); in 13 of them PM set in within 3 days of PQ ingestion. 15 patients died within 3 days of appearance of PM. Compared with patients without PM, those with PM were younger (P = 0.011), and had higher scores of Acute Physiology and Chronic Health Evaluation (P < 0.001) and Sequential Organ Failure Assessment (P = 0.003). In addition, patients with PM had a higher incidence of acute renal failure (P = 0.001), toxic hepatitis (P = 0.008), and respiratory insufficiency (P = 0.003). PM predicted an increased risk of 90-day death (93.8% of patients with PM vs. 40.7% among those without PM; hazard ratio [HR], 2.4; 95% confidence interval [CI], 1.0-5.6; P = 0.045), and increased risk of 5-day death (81.3% vs. 27.1%; HR, 3.2; 95% CI, 1.2-8.1; P = 0.017). DISCUSSION AND CONCLUSION: Early PM, occurring within 8 days, is a specific predictor of mortality in PQ poisoning.

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.

Serum paraquat concentration detected by spectrophotometry in patients with paraquat poisoning.

BACKGROUND: Paraquat (PQ) is a world-wide used herbicide and also a type of common poison for suicide and accidental poisoning. Numerous studies have proved that the concentration of serum PQ plays an important role in prognosis. Spectrophotometry, including common spectrophotometry and second-derivative spectrophotometry, is commonly used for PQ detection in primary hospitals. So far, lack of systematic research on the reliability of the method and the correlation between clinical features of patients with PQ poisoning and the test results has restricted the clinical use of spectrophotometry. This study aimed to evaluate the reliability and value of spectrophotometry in detecting the concentration of serum PQ. METHODS: The wavelengths for detecting the concentration of serum PQ by common and second-derivative spectrophotometry were determined. Second-derivative spectrophotometry was applied to detect the concentration of serum PQ. The linear range and precision for detection of PQ concentration by this method were confirmed. The concentration of serum PQ shown by second-derivative spectrophotometry and HPLC were compared in 8 patients with PQ poisoning. Altogether 21 patients with acute poisoning 4 hours after PQ ingestion treated in the period of October 2008 to September 2010 were retrospectively reviewed. The patients were divided into higher and lower than 1.8 µg/mL groups based on their concentrations of serum PQ measured by second-derivative spectrophotometry on admission. The severity of clinical manifestations between the two groups were analyzed with Student's t test or Fisher's exact test. RESULTS: The absorption peak of 257 nm could not be found when common spectrophotometry was used to detect the PQ concentration in serum. The calibration curve in the 0.4-8.0 µg/mL range for PQ concentration shown by second-derivative spectrophotometry obeyed Beer's law with r=0.996. The average recovery rates of PQ were within a range of 95.0% to 99.5%, relative standard deviation (RSD) was within 1.35% to 5.41% (n=6), and the lower detection limit was 0.05 µg/mL. The PQ concentrations in serum of 8 patients with PQ poisoning shown by second-derivative spectrophotometry were consistent with the quantitative determinations by HPLC (r=0.995, P<0.0001). The survival rate was 22.2% in patients whose PQ concentration in serum was more than 1.8 µg/mL, and the incidences of acidosis, oliguria and pneumomediastinum in these patients were 55.6%, 55.6% and 77.8%, respectively. These clinical manifestations were different significantly from those of the patients whose PQ concentration in serum was less than 1.8 µg/mL (P<0.05). CONCLUSIONS: For common spectrophotometry, the wavelength at 257 nm was not suitable for detecting serum PQ as no absorbance was shown. Second-derivative spectrophotometry was reliable for detecting serum paraquat concentration. Serum PQ concentration detected by second-derivative spectrophotometry could be used to predict the severity of clinical manifestations of patients with PQ poisoning, and PQ content higher than 1.8 µg/mL 4 hours after ingestion could be an important predictive factor for poor prognosis.

[Effects of metal-catalyzed oxidation on the formation of advanced oxidation protein products].

OBJECTIVE: To explore the relationship between metal-catalyzed oxidation (MCO) and the formation of advanced oxidation protein products (AOPPs). METHODS: Specimens of human serum albumin (HSA) and pooled plasma were collected from 3 healthy volunteers and 4 uremia patients were divided into 3 groups: Group A incubated with copper sulfate solution of the concentrations of 0, 0.2, or 0.5 mmol/L, Group B, incubated with hydrogen peroxide 2 mmol/L, and Group C, incubated with copper sulfate 0.2 or 0.5 mmol/L plus hydrogen peroxide 2 mmol/L. 30 min and 24 h later the AOPP level was determined by ultraviolet visible spectrophotometry. High-performance liquid chromatography (HPLC) was used to observe the fragmentation effect on plasma proteins. Ninhydrin method was used to examine the protein fragments. The scavenging capacity of hydroxyl radical by macromolecules was measured so as to estimate the extent of damage for proteins induced by MCO. RESULTS: (1) The AOPP level of the HSA and plasma specimens of the uremia patients increased along with the increase of cupric ion concentration in a dose-dependent manner, especially in the presence of hydrogen peroxide (P < 0.05). (2) Aggregation of proteins was almost negligible in all groups, however, HPLC showed that cupric ion with or without hydrogen peroxide increased the fragments in the HAS specimens (with a relative molecular mass of 5000) and uremia patients' plasma proteins (with the molecular mass 7000). (3) The plasma AOPP level of the healthy volunteers was 68.2 micromol/L +/- 2.4 micromol/L, significantly lower than that of the uremia patients (158.5 micromol/L +/- 8.2 micromol/L). (4) The scavenging ability to clear hydroxyl radical by plasma proteins of the healthy volunteers was 1.38 -9.03 times as higher than that of the uremia patients. CONCLUSION: MCO contributes to the formation of AOPPs mainly through its fragmentation effect to proteins.