Favorable evolution of severe paraquat poisoning. Treatment with gastric lavage, activated charcoal, cyclophosphamide + corticoids, and conventional daily hemodialysis: case study at the Franck Joly Hospital Center in French Guiana / Évolution favorable d'une intoxication grave au paraquat. Traitement par lavage gastrique, charbon activé, cyclophosphamide + corticoïdes, et hémodialyse conventionnelle quotidienne : étude des cas au centre hospitalier Franck Joly en Guyane française

We report the observations of two patients, having voluntarily ingested lethal doses of paraquat with suicidal intent, with an unfavorable prognostic score. The treatment consisted of gastric lavage, administration of activated charcoal, n-acetylcysteine and cyclophosphamide + methylprednisolone + dexamethasone. The installation of acute renal failure motivated the initiation of daily conventional hemodialysis (HD) over 10 to 14 days, with a favorable evolution. The following complications were recorded: anemia, bacteremia and deep vein thrombosis. These observations raise three questions in the treatment of paraquat intoxication: the effectiveness of HD, the interest of its association with the above therapies in the prevention of pulmonary fibrosis, and the need for infectious prevention and thromboembolism. Furthermore, the absence of a paraquatemia assay cannot constitute a limitation for management, and hemoperfusion on an inaccessible charcoal column can be replaced by an HD usually available.

Nous rapportons les observations de deux patients ayant ingéré volontairement des doses létales du paraquat à but suicidaire, avec un score pronostic défavorable. Le traitement a consisté en un lavage gastrique, une administration du charbon activé, du n-acétylcystéine et du cyclophosphamide + méthylprednisolone + dexaméthasone. L'installation d'une insuffisance rénale aiguë a motivé l'initiation d'une hémodialyse conventionnelle quotidienne (HD) sur 10 à 14 jours, avec une évolution favorable. Les complications suivantes ont été enregistrées : anémie, bactériémie et thrombose veineuse profonde. Ces observations soulèvent trois questions dans le traitement d'une intoxication au paraquat : l'efficacité de l'HD, l'intérêt de son association avec les thérapeutiques supra dans la prévention de la fibrose pulmonaire, et la nécessité d'une prévention infectieuse et thrombo-embolique. Par ailleurs, l'absence d'un dosage de la paraquatémie ne peut constituer une limite pour la prise en charge, et l'hémoperfusion sur colonne de charbon non accessible peut être remplacée par une HD habituellement disponible.

[The risk prediction value of paraquat poisoning dose, urine protein and myocardial enzymes].

Objective: To explore the value of paraquat (PQ) intake, urine protein and myocardial enzyme indexes in judging the prognosis of patients with acute PQ poisoning. Methods: From September to December 2021, all 201 patients with acute PQ poisoning admitted to Guangzhou Twelfth People's Hospital from January 2010 to December 2019 were selected as the research objects. Based on follow-up results 60 days after poisoning, the research objects were divided into survival group (n=78) and death group (n=123) . The differences in information about poisoning, treatment plan, PQ intake, urine protein, creatine kinase, creatine kinase isoenzyme, lactate dehydrogenase, and α-hydroxybutyrate dehydrogenase between the two groups of patients were compared and analyzed. Logistic regression and Cox regression were used to analyze the correlation between poisoning outcome and PQ intake, urine protein and myocardial enzymes. ROC curve and principal component analysis were used to explore high-efficiency indicators for predicting the outcome of acute PQ poisoning. Results: The PQ intake[50 (20, 100) ml], urine protein (total rank 15570.50) , creatine kinase[ (336.36±261.96) U/L], creatine kinase isoenzyme[ (43.91±43.74) U/L], lactate dehydrogenase [ (346.01±196.50) U/L], α-hydroxybutyrate dehydrogenase content[ (271.23±11.92) U/L] of patients in the death group were all higher than the survival group[15 (10, 20) ml, 4730.50, (187.78±178.06) U/L, (18.88±15.50) U/L, (190.92±60.50) U/L, (152.60±48.34) U/L, respectively] (P<0.05) . The outcome of acute PQ poisoning was positively correlated with PQ intake, urine protein, creatine kinase, creatine kinase isoenzyme, lactate dehydrogenase, and α-hydroxybutyrate dehydrogenase (P<0.05) . Multivariate logistic regression and multivariate Cox regression analysis showed that creatine kinase, creatine kinase isoenzyme, lactate dehydrogenase and α-hydroxybutyrate dehydrogenase was positively correlated with the prognosis of patients with acute PQ poisoning (P<0.05) . ROC curve analysis and principal component analysis showed that the combined indexes of PQ intake, urine protein and myocardial enzymes had the highest efficacy and weight in judging the prognosis of patients (AUC=0.91, weight coefficient=0.19, sensitivity=0.76, specificity=0.89) . When the combined score was ≥4, the probability of accurately predicting the death of patients was as high as 91% (positive predictive value=0.91) . Conclusion: PQ intake, urine protein combined with creatine kinase, creatine kinase isoenzyme, lactate dehydrogenase, and α-hydroxybutyrate dehydrogenase has high value in predicting the prognosis of patients with acute PQ poisoning.

Intoxicación fatal con paraquat por vía dérmica. Reporte de caso / Fatal paraquat poisoning by dermal exposure. Case report

Introducción: Por su alta letalidad el paraquat® es utilizado con fines suicidas, siendo la principal vía de uso, la oral; los casos por vía cutánea son escasos y raras veces son fatales. Este reporte presenta un caso de compromiso sistémico severo y muerte después de exposición dérmica a paraquat® . Resumen del caso: Paciente femenina de 47 años, soltera, ama de casa, de procedencia rural, con secundaria incompleta; e historia de aplicación de paraquat® en ulcera. A las 24h de aplicación presento fiebre, vómito y malestar general; al ingreso hospitalario presento además ictericia generalizada, insuficiencia renal aguda, insuficiencia respiratoria, deterioro progresivo de su estado de salud y muerte, por lo que fue remitida a autopsia médico legal. Los hallazgos de autopsia descartaron la ingesta oral y mostraron páncreas hemorrágico, riñones congestivos, hígado de tamaño aumentado (2550g) y hemorrágico, corazón aumentado de tamaño. Los estudios histopatológicos mostraron daño alveolar difuso, (membranas hialinas, edema y hemorragia); neumonía en pulmón y congestión visceral generalizada...(AU)

The risk prediction value of paraquat poisoning dose, urine protein and myocardial enzymes / 中华劳动卫生职业病杂志

Objective: To explore the value of paraquat (PQ) intake, urine protein and myocardial enzyme indexes in judging the prognosis of patients with acute PQ poisoning. Methods: From September to December 2021, all 201 patients with acute PQ poisoning admitted to Guangzhou Twelfth People's Hospital from January 2010 to December 2019 were selected as the research objects. Based on follow-up results 60 days after poisoning, the research objects were divided into survival group (n=78) and death group (n=123) . The differences in information about poisoning, treatment plan, PQ intake, urine protein, creatine kinase, creatine kinase isoenzyme, lactate dehydrogenase, and α-hydroxybutyrate dehydrogenase between the two groups of patients were compared and analyzed. Logistic regression and Cox regression were used to analyze the correlation between poisoning outcome and PQ intake, urine protein and myocardial enzymes. ROC curve and principal component analysis were used to explore high-efficiency indicators for predicting the outcome of acute PQ poisoning. Results: The PQ intake[50 (20, 100) ml], urine protein (total rank 15570.50) , creatine kinase[ (336.36±261.96) U/L], creatine kinase isoenzyme[ (43.91±43.74) U/L], lactate dehydrogenase [ (346.01±196.50) U/L], α-hydroxybutyrate dehydrogenase content[ (271.23±11.92) U/L] of patients in the death group were all higher than the survival group[15 (10, 20) ml, 4730.50, (187.78±178.06) U/L, (18.88±15.50) U/L, (190.92±60.50) U/L, (152.60±48.34) U/L, respectively] (P<0.05) . The outcome of acute PQ poisoning was positively correlated with PQ intake, urine protein, creatine kinase, creatine kinase isoenzyme, lactate dehydrogenase, and α-hydroxybutyrate dehydrogenase (P<0.05) . Multivariate logistic regression and multivariate Cox regression analysis showed that creatine kinase, creatine kinase isoenzyme, lactate dehydrogenase and α-hydroxybutyrate dehydrogenase was positively correlated with the prognosis of patients with acute PQ poisoning (P<0.05) . ROC curve analysis and principal component analysis showed that the combined indexes of PQ intake, urine protein and myocardial enzymes had the highest efficacy and weight in judging the prognosis of patients (AUC=0.91, weight coefficient=0.19, sensitivity=0.76, specificity=0.89) . When the combined score was ≥4, the probability of accurately predicting the death of patients was as high as 91% (positive predictive value=0.91) . Conclusion: PQ intake, urine protein combined with creatine kinase, creatine kinase isoenzyme, lactate dehydrogenase, and α-hydroxybutyrate dehydrogenase has high value in predicting the prognosis of patients with acute PQ poisoning.

Ginkgolide C Alleviates Acute Lung Injury Caused by Paraquat Poisoning via Regulating the Nrf2 and NF-κB Signaling Pathways.

Paraquat (PQ), a highly toxic herbicide and primary attack for lung, results in severe acute lung injury (ALI) appeared as evident oxidative stress, inflammation, and apoptosis. Increasing evidence elucidates that nuclear factor erythroid-2-related factor 2 (Nrf2) and its associated nuclear factor-κB (NF-κB) exhibit many merits for protection of ALI by coordinating a fine-turned response to oxidative stress, inflammation, and apoptosis. Ginkgolide C (GC) has been reported to be a safe and potent therapeutic agent against ALI. However, whether GC could protect ALI induced by PQ poisoning and the possible underlining mechanisms have remained not to be fully elucidated. A rat model of ALI and a model of acute type II alveolar epithelial cell (RLE-6TN) injury constructed by exposure to PQ were applied to discuss the protective effect of GC. Furthermore, Nrf2 gene silencing RLE-6TN cells were used to discuss the exact mechanism. We confirmed that GC significantly ameliorated the histopathological damages, ultrastructural changes, lung injury score, W/D ratio, and Hyp activity of lung tissue and inhibited polymorphonuclear neutrophil (PMN) infiltration after PQ poisoning. Further results revealed that GC remarkably activated Nrf2-based cytoprotective system and inhibited NF-κB-induced inflammatory injury as well as apoptosis. Taken together, we concluded that GC preserved protection of PQ-induced ALI via the Nrf2-NF-κB dependent signal pathway, which may provide us novel insights into the treatment strategies for PQ poisoning.

MicroRNA-200b-3p as a biomarker for diagnosis and survival prognosis of multiple organ dysfunction syndrome caused by acute paraquat poisoning.

BACKGROUND: Acute paraquat poisoning-induced multiple organ dysfunction syndrome (MODS) leads to the high mortality. This study aimed to investigate the clinical significance of microRNA-200b-3p (miR-200b-3p), an upstream inhibitor of high-mobility group box 1 (HMGB1), in acute paraquat poisoning patients for the prediction of MODS and survival. METHODS: This study enrolled 80 patients with MODS induced by paraquat and 94 healthy volunteers. The interaction between miR-200b-3p and HMGB1 was identified by luciferase reporter assay. miR-200b-3p levels were measured by quantitative real-time (QRT) PCR. High-mobility group box 1 levels were measured by enzyme-linked immune sorbent assay (ELISA). Receiver operating characteristic analysis was used to evaluate the diagnostic value of miR-200b-3p in screening MODS patients. The relationship between miR-200b-3p and the 28-day survival of MODS patients was evaluated by Kaplan-Meier curves and log-rank test. Cox regression analysis was used to assess the prognostic value of miR-200b-3p. Correlation between miR-200b-3p and HMGB1 was confirmed by Pearson's correlation analysis. RESULTS: miR-200b-3p directly target HMGB1. miR-200b-3p, decreased in MODS patients, had high diagnostic value to screen MODS patients from healthy controls. Additionally, serum miR-200b-3p was decreased in non-survivors, and patients with low miR-200b-3p level had poor 28-day survival. Serum miR-200b-3p could independently predict the survival prognosis. Moreover, serum HMGB1 level was increased in MODS patients, and was negatively correlated with miR-200b-3p level. CONCLUSION: Decreased miR-200b-3p may function as a biomarker for the diagnosis and survival prognosis of MODS patients, and miR-200b-3p may be involved in the progression of acute paraquat-induced MODS via regulating inflammatory responses by targeting HMGB1.

Identification of differentially expressed genes and pathways in diquat and paraquat poisoning using bioinformatics analysis.

OBJECTIVE: In this study, differentially expressed genes (DEGs) and signaling pathways involved in diquat (DQ) and paraquat (PQ) poisoning were identified via bioinformatics analysis, in order to inform the development of novel clinical treatments. METHODS: Raw data from GSE153959 were downloaded from the Gene Expression Omnibus database. DEGs of the DQ vs. control (CON) and PQ vs. CON comparison groups were identified using R, and DEGs shared by the two groups were identified using TBtools. Subsequently, the shared DEGs were searched in the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases, using the Database for Annotation, Visualization, and Integrated Discovery. A protein-protein interaction (PPI) network was constructed, and hub genes were identified using the cytoHubba plug-in in Cytoscape software. Finally, circos and contrast plots showing the DEGs shared between mouse and human chromosomes were constructed using TBtools. RESULTS: Thirty-one DEGs shared by the DQ and PQ groups were identified. Enriched biological process terms included positive regulation of cell proliferation and translation. Enriched cellular component terms included extracellular region, intracellular membrane-bounded organelle and mitochondrion. Enriched molecular function terms included transcription factor activity and sequence-specific double-stranded DNA binding. Enriched KEGG pathways included the interleukin-17 signaling pathway, tumor necrosis factor signaling pathway, and human T-cell leukemia virus 1 infection. The top 10 hub genes in the PPI network were prostaglandin-endoperoxide synthase 2 (Ptgs2), chemokine (C-X-C motif) ligand 2 (Cxcl2), colony-stimulating factor 2 (granulocyte-macrophage) (Csf2), matrix metallopeptidase 13 (Mmp13), amphiregulin (Areg), plasminogen activator, urokinase receptor (Plaur), fos-like antigen 1 (Fosl1), epiregulin (Ereg), activating transcription factor 3 (Atf3), and transferrin receptor (Tfrc). Cxcl2, Csf2, and Atf3 played important roles in the mitogen-activated protein kinase (MAPK) signaling pathway. CONCLUSIONS: These pathways and DEGs may serve as targets for gene therapy.

Hallazgos en imágenes de tórax en una intoxicación aguda con paraquat: reporte de un caso / Findings on thorax images in acute paraquat poisoning: case report

Resumen El Paraquat es un herbicida ampliamente utilizado para el control de las malezas en Chile. Su ingesta determina una alta probabilidad de mortalidad dado su inherente toxicidad mediante la producción de radicales libres, que afectan a múltiples órganos, principalmente los pulmones; a esto se suma la falta de un tratamiento efectivo. Se presenta el caso clínico de un hombre de 18 años que en un intento suicida consume 50 mL de paraquat (200 g/L), con desenlace fatal. La presentación clínica depende la cantidad de Paraquat ingerida y los hallazgos radiológicos descritos varían según la temporalidad del cuadro e, inclusive, podrían determinar el pronóstico.

Paraquat is an herbicide widely used for weed control in Chile. Its intake determines a high probability of mortality because of its inherent toxicity through the production of free radicals. Multiple organs are affected, mainly the lungs; to this is added the lack of effective treatment. We present the clinical case of an 18-year-old man who in a suicidal attempt swallows 50 mL of paraquat (200 g/L), with a fatal outcome. The clinical presentation depends on the amount of Paraquat ingested. Radiological findings described vary according to the temporality of the condition and could even determine the prognosis

Anthrahydroquinone-2-6-disulfonate is a novel, powerful antidote for paraquat poisoning.

Paraquat (PQ) is a widely used fast-acting pyridine herbicide. Accidental ingestion or self-administration via various routes can cause severe organ damage. Currently, no effective antidote is available commercially, and the mortality rate of poisoned patients is exceptionally high. Here, the efficacy of anthrahydroquinone-2-6-disulfonate (AH2QDS) was observed in treating PQ poisoning by constructing in vivo and ex vivo models. We then explored the detoxification mechanism of AH2QDS. We demonstrated that, in a rat model, the PQ concentration in the PQ + AH2QDS group significantly decreased compared to the PQ only group. Additionally, AH2QDS protected the mitochondria of rats and A549 cells and decreased oxidative stress damage, thus improving animal survival and cell viability. Finally, the differentially expressed genes were analysed in the PQ + AH2QDS group and the PQ group by NextGen sequencing, and we verified that Nrf2's expression in the PQ + AH2QDS group was significantly higher than that in the PQ group. Our work identified that AH2QDS can detoxify PQ by reducing PQ uptake and protecting mitochondria while enhancing the body's antioxidant activity.

A novel flowchart to predict mortality and analyse effectiveness of routinely used pharmacological regimens in paraquat poisoning.

Paraquat is responsible for an extremely high case-fatality rate poisoning. Mortality prediction remains a major issue since evidence to support benefits of routinely used treatments is lacking. We aimed to develop an easy-to-use prediction flowchart not requiring the ingestion time, for which accuracy is frequently questionable, and to evaluate the effectiveness of routinely used pharmacological therapies on mortality. We designed a two-centre cohort study including consecutive paraquat-poisoned adults with confirmed diagnosis based on serum/urine paraquat measurement. We built a flowchart using a multivariate analysis of death predictors and analysed the outcome according to the administered therapies. Overall, 256 patients were enrolled. Mortality rate was 75%. Independent death predictors on admission were serum creatinine (odds ratio [OR], 5.07; 95% confidence interval [CI], 1.97-13.05) and serum paraquat concentration (OR, 2.26; CI, 1.66-3.09). The area-under-the flowchart curve was 0.91. Overall sensitivity and specificity were 81.5% and 94.8%, respectively. More survivors than non-survivors of severe poisoning received methylprednisolone (P = 0.04). While not significantly differing in severity, methylprednisolone-treated patients had better survival (P = 0.04). To conclude, we defined an efficient flowchart to predict mortality in paraquat poisoning at presentation, even if ingestion time is undetermined. Methylprednisolone seems effective to improve the outcome, especially in the most severe cases.

Thoracic radiographic features of fatal paraquat intoxication in eleven dogs.

BACKGROUND: Paraquat (1,1-dimethyl-4,4-bipyridinium dichloride) is a toxic herbicide. Accidental ingestion of paraquat in animals and humans causes respiratory failure and death. AIM: To describe the radiographic features of confirmed paraquat intoxication in a group of dogs and determines whether any identified features can facilitate this diagnosis. METHODS: Eleven dogs diagnosed with paraquat intoxication were selected from two institutions between November 2014 and August 2019 comprising five males (all intact) and six females (one intact and five spayed). The mean age was 3.9 ± 2.9 (SD) years and their mean weight was 11.6 ± 5.0 kg. The tentative diagnosis was confirmed through analysis of their urine samples using a colorimetric assay (paraquat concentation 0.39 µg/ml ranging from 0.19-0.65 µg/ml), and their clinical signs were reviewed. Thoracic radiographs were evaluated for the presence of pneumomediastinum, lung patterns (interstitial or alveolar) and their locations (caudodorsal, cranioventral, diffuse, or symmetrical), subcutaneous emphysema, pneumoretroperitoneum, and pneumothorax. RESULTS: The most common clinical signs were dyspnea (11/11, 100%) and anorexia (9/11, 82%). Pneumomediastinum (10/11, 91%) and symmetrically increased lung opacity (7/11, 65%) were the most common radiographic features. Pneumothorax (3/11, 27%), pleural effusion (3/11, 27%), subcutaneous emphysema (2/11, 18%), and pneumoretroperitoneum (1/5, 20%) were the less common findings. None of the dogs survived. CONCLUSION: Pneumomediastinum and diffuse or symmetrical interstitial or alveolar lung patterns are the most common radiographic features in dogs with paraquat intoxication. CLINICAL RELEVANCE: In countries where this herbicide is not banned, paraquat intoxication should be considered if dogs with no history of trauma present with pneumomediastinum.

Glucocorticoid with cyclophosphamide for oral paraquat poisoning.

BACKGROUND: This an update of a Cochrane Review. Paraquat is a widely used herbicide, but is also a lethal poison. In some low- and middle-income countries (LMICs) paraquat is commonly available and inexpensive, making poisoning prevention difficult. Most of the people poisoned by paraquat have taken it as a means of self-poisoning. Standard treatment for paraquat poisoning prevents further absorption and reduces the load of paraquat in the blood through haemoperfusion or haemodialysis. The effectiveness of standard treatments is extremely limited. The immune system plays an important role in exacerbating paraquat-induced lung fibrosis. Immunosuppressive treatment using glucocorticoid and cyclophosphamide in combination has been developed and studied as an intervention for paraquat poisoning. OBJECTIVES: To assess the effects of glucocorticoid with cyclophosphamide for moderate to severe oral paraquat poisoning. SEARCH METHODS: The most recent searches were run in September 2020. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Injuries Trials Register), Ovid MEDLINE(R), Ovid MEDLINE In-Process & Other Non-Indexed Citations, Ovid MEDLINE Daily and Ovid OLDMEDLINE, Embase Classic + Embase (Ovid), ISI WOS (SCI-EXPANDED, SSCI, CPCI-S, and CPSI-SSH), and trials registries. We also searched the following three resources: China National Knowledge Infrastructure database (CNKI ); Wanfang Data (); and VIP () on 12 November 2020. We examined the reference lists of included studies and review papers. SELECTION CRITERIA: We included randomised controlled trials (RCTs). For this update, in accordance with Cochrane Injuries' Group policy (2015), we included only prospectively registered RCTs for trials published after 2010. We included trials which assessed the effects of glucocorticoid with cyclophosphamide delivered in combination. Eligible comparators were standard care (with or without a placebo), or any other therapy in addition to standard care. Outcomes of interest included mortality and infections. DATA COLLECTION AND ANALYSIS: We calculated the mortality risk ratio (RR) and 95% confidence interval (CI). Where possible, we summarised data for all-cause mortality at relevant time periods (from hospital discharge to three months after discharge) in meta-analysis, using a fixed-effect model. We conducted sensitivity analyses based on factors including whether participants were assessed at baseline for plasma paraquat levels. We also reported data on infections within one week after initiation of treatment. MAIN RESULTS: We included four trials with a total of 463 participants. The included studies were conducted in Taiwan (Republic of China), Iran, and Sri Lanka. Most participants were male. The mean age of participants was 28 years. We judged two of the four included studies, including the largest and most recently conducted study (n = 299), to be at low risk of bias for key domains including sequence generation. We assessed one study to be at high risk of selection bias and another at unclear risk, since allocation concealment was either not mentioned in the trial report or explicitly not undertaken. We assessed three of the four studies to be at unclear risk of selective reporting, as no protocols could be identified. An important source of heterogeneity amongst the included studies was the method of assessment of participants' baseline severity using analysis of plasma levels (two studies employed this method, whilst the other two did not). No studies assessed the outcome of mortality at 30 days following ingestion of paraquat. Low-certainty evidence from two studies indicates that glucocorticoids with cyclophosphamide in addition to standard care may slightly reduce the risk of death in hospital compared to standard care alone ((RR 0.82, 95% CI 0.68 to 0.99; participants = 322); results come from sensitivity analysis excluding studies not assessing plasma at baseline). However, we have limited confidence in this finding as heterogeneity was high (I2 = 77%) and studies varied in terms of size and comparators. A single large study provided data showing that there may be little or no effect of treatment at three months post discharge from hospital (RR 0.98, 95% CI 0.85 to 1.13; 1 study, 293 participants; low-certainty evidence); however, analysis of long-term results amongst participants whose injuries arose from self-poisoning must be interpreted with caution. We remain uncertain of the effect of glucocorticoids with cyclophosphamide on infection within one week after initiation of the treatment; this outcome was assessed by two small studies only (31 participants, very low-certainty evidence) that considered leukopenia as a proxy or risk factor for infection. Neither study reported infections in any participants. AUTHORS' CONCLUSIONS: Low-certainly evidence suggests that glucocorticoids with cyclophosphamide in addition to standard care may slightly reduce mortality in hospitalised people with oral paraquat poisoning. However, we have limited confidence in this finding because of substantial heterogeneity and concerns about imprecision. Glucocorticoids with cyclophosphamide in addition to standard care may have little or no effect on mortality at three months after hospital discharge. We are uncertain whether glucocorticoid with cyclophosphamide puts patients at an increased risk of infection due to the limited evidence available for this outcome. Future research should be prospectively registered and CONSORT-compliant. Investigators should attempt to ensure an adequate sample size, screen participants for inclusion rigorously, and seek long-term follow-up of participants. Investigators may wish to research the effects of glucocorticoid in combination with other treatments.

Urinary microRNAs as non-invasive biomarkers for toxic acute kidney injury in humans.

MicroRNAs in biofluids are potential biomarkers for detecting kidney and other organ injuries. We profiled microRNAs in urine samples from patients with Russell's viper envenoming or acute self-poisoning following paraquat, glyphosate, or oxalic acid [with and without acute kidney injury (AKI)] and on healthy controls. Discovery analysis profiled for 754 microRNAs using TaqMan OpenArray qPCR with three patients per group (12 samples in each toxic agent). From these, 53 microRNAs were selected and validated in a larger cohort of patients (Russell's viper envenoming = 53, paraquat = 51, glyphosate = 51, oxalic acid = 40) and 27 healthy controls. Urinary microRNAs had significantly higher expression in patients poisoned/envenomed by different nephrotoxic agents in both discovery and validation cohorts. Seven microRNAs discriminated severe AKI patients from no AKI for all four nephrotoxic agents. Four microRNAs (miR-30a-3p, miR-30a-5p, miR-92a, and miR-204) had > 17 fold change (p < 0.0001) and receiver operator characteristics area-under-curve (ROC-AUC) > 0.72. Pathway analysis of target mRNAs of these differentially expressed microRNAs showed association with the regulation of different nephrotoxic signaling pathways. In conclusion, human urinary microRNAs could identify toxic AKI early after acute injury. These urinary microRNAs have potential clinical application as early non-invasive diagnostic AKI biomarkers.

Development and Validation of a Radiomics Nomogram for Prognosis Prediction of Patients with Acute Paraquat Poisoning: A Retrospective Cohort Study.

OBJECTIVE: To evaluate the efficiency of a radiomics model in predicting the prognosis of patients with acute paraquat poisoning (APP). MATERIALS AND METHODS: Chest computed tomography images and clinical data of 80 patients with APP were obtained from November 2014 to October 2017, which were randomly assigned to a primary group and a validation group by a ratio of 7 : 3, and then the radiomics features were extracted from the whole lung. Principal component analysis (PCA) and least absolute shrinkage and selection operator (LASSO) regression were used to select the features and establish the radiomics signature (Rad-score). Multivariate logistic regression analysis was used to establish a radiomics prediction model incorporating the Rad-score and clinical risk factors; the model was represented by nomogram. The performance of the nomogram was confirmed by its discrimination and calibration. RESULT: The area under the ROC curve of operation was 0.942 and 0.865, respectively, in the primary and validation datasets. The sensitivity and specificity were 0.864 and 0.914 and 0.778 and 0.929, and the prediction accuracy rates were 89.5% and 87%, respectively. Predictors included in the individualized predictive nomograms include the Rad-score, blood paraquat concentration, creatine kinase, and serum creatinine. The AUC of the nomogram was 0.973 and 0.944 in the primary and validation datasets, and the sensitivity and specificity were 0.943 and 0.955, respectively, in the primary dataset and 0.889 and 0.929 in the validation dataset, and the prediction accuracy was 94.7% and 91.3%, respectively. CONCLUSION: The radiomics nomogram incorporates the radiomics signature and hematological laboratory data, which can be conveniently used to facilitate the individualized prediction of the prognosis of APP patients.

Association between liberal oxygen therapy and mortality in patients with paraquat poisoning: A multi-center retrospective cohort study.

Paraquat (N, N'-dimethyl-4, 4'-bipyridinium dichloride, PQ) intoxication is a common cause of lethal poisoning. This study aimed to identify the risk of using liberal oxygen therapy in patients with PQ poisoning. This was a multi-center retrospective cohort study involving four medical institutions in Taiwan. Data were extracted from the Chang Gung Research Database (CGRD) from January 2004 to December 2016. Patients confirmed to have PQ intoxication with a urine PQ concentration ≥ 5 ppm were analyzed. Patients who received oxygen therapy before marked hypoxia (SpO2 ≥ 90%) were defined as receiving liberal oxygen therapy. The association between mortality and patient demographics, blood paraquat concentration (ppm), and liberal oxygen therapy were analyzed. A total of 416 patients were enrolled. The mortality rate was higher in the liberal oxygen therapy group (87.8% vs. 73.7%, P = 0.007), especially in 28-day mortality (adjusted odds ratio [aOR]: 4.71, 95% confidence interval [CI]: 1.533-14.471) and overall mortality (aOR: 5.97, 95% CI: 1.692-21.049) groups. Mortality in patients with PQ poisoning was also associated with age (aOR: 1.04, 95% CI: 1.015-1.073), blood creatinine level (aOR: 1.49, 95% CI: 1.124-1.978), and blood paraquat concentration (ppm) (aOR, 1.51; 95% CI: 1.298-1.766). Unless the evidence of hypoxia (SpO2 < 90%) is clear, oxygen therapy should be avoided because it is associated with increased mortality.

Prognostic value of liver and kidney function parameters and their correlation with the ratio of urine-to-plasma paraquat in patients with paraquat poisoning.

Acute paraquat poisoning resulting from multiple organ failure usually has a high mortality rate. Liver and kidney, as the key oranges of paraquat detoxification and elimination, their injuries may suppress toxin excretion and enhance the toxicity of paraquat in other organs and worsen the prognosis. Therefore, we intended to explore the prognostic value of liver and kidney function parameters, and further evaluate their correlation with a more stable index urine-to-plasma paraquat (urine paraquat concentrations/plasma paraquat concentrations) instead of considering paraquat concentrations in plasma or urine alone. The study included 33 patients with acute paraquat poisoning admitted to four centres in China from January 2018 to December 2019. Seventeen patients (10 male/7 female) survived, whereas 16 patients (7 male/9 female, 48.48%) died from paraquat poisoning. Alanine aminotransferase (ALT) and the blood urea nitrogen (BUN) represent liver and kidney function parameters, respectively. The ratio of urine-to-plasma paraquat is negatively correlated with ALT (r = -0.94, P = 0 .02) and BUN (r = -0.82, P = 0.03). For receiver operating characteristic curve (ROC) analysis, ALT, BUN and urine-to-plasma paraquat have an AUC over 0.80. The study shows that the functional indexes of liver and kidney, as well as the ratio of urine-to-plasma paraquat, could be considered for evaluating the extent of organ injury and excretion rate of paraquat.

A novel simple risk model to predict the prognosis of patients with paraquat poisoning.

To identify risk factors and develop a simple model to predict early prognosis of acute paraquat (PQ) poisoning patients, we performed a retrospective cohort study of acute PQ poisoning patients (n = 1199). Patients (n = 913) with PQ poisoning from 2011 to 2018 were randomly divided into training (n = 609) and test (n = 304) samples. Another two independent cohorts were used as validation samples for a different time (n = 207) and site (n = 79). Risk factors were identified using a logistic model with Markov Chain Monte Carlo (MCMC) simulation and further evaluated using a latent class analysis. The prediction score was developed based on the training sample and was evaluated using the testing and validation samples. Eight factors, including age, ingestion volume, creatine kinase-MB [CK-MB], platelet [PLT], white blood cell [WBC], neutrophil counts [N], gamma-glutamyl transferase [GGT], and serum creatinine [Cr] were identified as independent risk indicators of in-hospital death events. The risk model had C statistics of 0.895 (95% CI 0.855-0.928), 0.891 (95% CI 0.848-0.932), and 0.829 (95% CI 0.455-1.000), and predictive ranges of 4.6-98.2%, 2.3-94.9%, and 0-12.5% for the test, validation_time, and validation_site samples, respectively. In the training sample, the risk model classified 18.4%, 59.9%, and 21.7% of patients into the high-, average-, and low-risk groups, with corresponding probabilities of 0.985, 0.365, and 0.03 for in-hospital death events. We developed and evaluated a simple risk model to predict the prognosis of patients with acute PQ poisoning. This risk scoring system could be helpful for identifying high-risk patients and reducing mortality due to PQ poisoning.

Pneumoperitoneum from pneumomediastinum in paraquat poisoning.

Pneumomediastinum is not uncommon in paraquat poisoning and usually results from oesophageal perforation or alveolar rupture in fibrotic lung disease. However, the combined presentation of pneumomediastinum and pneumoperitoneum is a rarity. We recently managed a young patient with paraquat ingestion who developed spontaneous pneumomediastinum. His chest radiograph also showed free air under the right hemidiaphragm. This pneumoperitoneum caused no clinical symptom and resolved spontaneously within a few days without any surgical intervention.

Simultaneous determination of paraquat and diquat in human plasma by HPLC-DAD: Its application in acute poisoning patients induced by these two herbicides.

BACKGROUND: Paraquat and diquat are widely used in agricultural production in many countries, which are very toxic to human beings. Paraquat can be detected in some diquat solution sold in the market. The blood concentration of paraquat or diquat is an important indicator for clinical diagnosis of paraquat or diquat poisoning. So, it is very meaningful to develop a method for simultaneous determination of paraquat and diquat in human plasma. OBJECTIVE: To develop and validate a HPLC-DAD method for simultaneous determination of paraquat and diquat in human plasma and to apply it in the acute poisoning patients by these two herbicides. METHODS: Paraquat and diquat were simultaneously determined by HPLC-DAD. The plasma was treated using Waters OASIS® Column and then separated on a Thermo Hypersil GOLD (250 × 4.6 mm, 5 µm) Column with the mobile phase consisted of 75 mmol/L sodium heptane sulfonate (containing 0.1 mol/L phosphoric acid, pH 3.0) and acetonitrile (87:13, v:v) at a flow rate of 1.0 mL/min. The full-wavelength scanning was 200-400 nm, and the detection wavelength of paraquat and diquat was 257nm and 310nm, respectively. 120 and 30 plasma samples from patients with paraquat and diquat poisoning were collected and analyzed by the established method. RESULTS: The standard curve for paraquat and diquat ranged from 0.05 to 20 µg/mL, and the precision of LLOQ for paraquat was 16.49%, which was required to be less than 20%. The precision of other concentrations was less than 14.14%. The recovery of paraquat and diquat was 95.38%-103.97% and 94.79%-98.40%, respectively. The results showed that paraquat and diquat were stable under various storage conditions. 120 plasma samples of paraquat poisoning patients and 30 plasma samples of diquat poisoning patients were determined by the established method. The blood concentration of paraquat ranged from 0.10 to 20.62 µg/mL, with an average of 3.61 µg/mL, while for diquat, the concentration ranged from 0 to 26.59 µg/mL, with an average of 2.00 µg/mL. Among the diquat suspected poisoning samples, 5 samples were detected not only diquat but also paraquat, and 2 samples were detected only paraquat, no diquat. CONCLUSION: The HPLC-DAD method established in this study was high throughput, high sensitivity, simple operation, and wide linear ranges. It can be used for the screening analysis and quantitative detection of paraquat and diquat in acute poisoning patients, which can provide basis for the treatment and prognosis of these two herbicides poisoning patients.