Prediction the prognosis of the poisoned patients undergoing hemodialysis using machine learning algorithms.

BACKGROUND: Hemodialysis is a life-saving treatment used to eliminate toxins and metabolites from the body during poisoning. Despite its effectiveness, there needs to be more research on this method precisely, with most studies focusing on specific poisoning. This study aims to bridge the existing knowledge gap by developing a machine-learning prediction model for forecasting the prognosis of the poisoned patient undergoing hemodialysis. METHODS: Using a registry database from 2016 to 2022, this study conducted a retrospective cohort study at Loghman Hakim Hospital. First, the relief feature selection algorithm was used to identify the most important variables influencing the prognosis of poisoned patients undergoing hemodialysis. Second, four machine learning algorithms, including extreme gradient boosting (XGBoost), histgradient boosting (HGB), k-nearest neighbors (KNN), and adaptive boosting (AdaBoost), were trained to construct predictive models for predicting the prognosis of poisoned patients undergoing hemodialysis. Finally, the performance of paired feature selection and machine learning (ML) algorithm were evaluated to select the best models using five evaluation metrics including accuracy, sensitivity, specificity the area under the curve (AUC), and f1-score. RESULT: The study comprised 980 patients in total. The experimental results showed that ten variables had a significant influence on prognosis outcomes including age, intubation, acidity (PH), previous medical history, bicarbonate (HCO3), Glasgow coma scale (GCS), intensive care unit (ICU) admission, acute kidney injury, and potassium. Out of the four models evaluated, the HGB classifier stood out with superior results on the test dataset. It achieved an impressive mean classification accuracy of 94.8%, a mean specificity of 93.5 a mean sensitivity of 94%, a mean F-score of 89.2%, and a mean receiver operating characteristic (ROC) of 92%. CONCLUSION: ML-based predictive models can predict the prognosis of poisoned patients undergoing hemodialysis with high performance. The developed ML models demonstrate valuable potential for providing frontline clinicians with data-driven, evidence-based tools to guide time-sensitive prognosis evaluations and care decisions for poisoned patients in need of hemodialysis. Further large-scale multi-center studies are warranted to validate the efficacy of these models across diverse populations.

Montelukast Is Effective in Treating Rhabdomyolysis Due to Intoxication: A Randomized Clinical Trial.

INTRODUCTION: Rhabdomyolysis is a clinical syndrome accompanied with biochemical changes that is diagnosed in some patients with acute chemical or drug poisoning. In this regard, the present study aimed to evaluate the effects of Montelukast in the treatment of intoxication-induced rhabdomyolysis. METHODS: This single-blind randomized clinical trial study was conducted in Loghman Hakim Hospital from March 2021 to March 2022. The study participants were 60 individuals evenly distributed into experimental and control groups. The experimental group received Montelukast plus routine treatment and the control group Creatine phosphokinase (CPK), urea, creatinine, aspartate aminotransferase (AST) and alanine transaminase (ALT) levels were monitored daily in both groups for seven days. The variables of age, gender and history of diabetes mellitus and kidney diseases were recorded. RESULTS: The mean age was 39.9 ± 16.87 and 38.2 ± 16.3 years in the control and intervention groups, respectively. Montelukast significantly (P < .05) reduced CPK levels on days five and seven, urea on days three, four, five and seven, and creatinine on days two to seven. The AST and ALT levels, unlike the control group which has a decreasing trend, increased first in the Montelukast group and then decreased on the sixth and seventh days. CONCLUSION: The results showed that Montelukast effectively reduced CPK, urea and creatinine levels, as well as the recovery time in patients with poison-induced rhabdomyolysis. In other words, Montelukast is effective in the treatment of rhabdomyolysis.  DOI: 10.52547/ijkd.7222.

Comparing Two Naloxone Tapering Methods in Management of Methadone Intoxication; a Quasi-experimental Study.

Introduction: Even though naloxone is the main treatment for methadone poisoning treatment there are controversies about the proper method of its tapering. This study aimed to compare two methods in this regard. Method: This study was a prospective, single-blind pilot quasi-experimental study on non-addicted adult patients poisoned with methadone. Patients were randomly divided into 2 groups. In one group, after stabilization of respiratory conditions and consciousness, naloxone was tapered using the half-life of methadone and in the other group, naloxone was tapered using the half-life of naloxone. Recurrence of symptoms and changes in venous blood gas parameters were compared between groups as outcome. Results: 52 patients were included (51.92% female). 31 cases entered Group A (tapering based on methadone's half-life) and 21 cases entered Group B (tapering based on naloxone's half-life). The two groups were similar regarding mean age (p = 0.575), gender distribution (p = 0.535), the cause of methadone use (p = 0.599), previous medical history (p = 0.529), previous methadone use (p = 0.654), drug use history (p = 0.444), and vital signs on arrival to emergency department (p = 0.054). The cases of re-decreasing consciousness during tapering (52.38% vs. 25.81%; p = 0.049) and after discontinuation of naloxone (72.73% vs. 37.50%; p = 0.050) were higher in the tapering based on naloxone half-life group. The relative risk reduction (RRR) for naloxone half-life group was -1.03 and for methadone half-life group was 0.51. The absolute risk reduction (ARR) was 0.27 (95% confidence interval (CI) = 0.01-0.53) and the number needed to treat (NNT) was 3.7 (95% CI= 1.87- 150.53). There was not any statistically significant difference between groups regarding pH, HCO3, and PCO2 changes during tapering and after naloxone discontinuation (p > 0.05). However, repeated measures analysis of variance (ANOVA), showed that in the tapering based on methadone's half-life group, the number of changes and stability in the normal range were better (p < 0.001). Conclusion: It seems that, by tapering naloxone based on methadone's half-life, not only blood acid-base disorders are treated, but they also remain stable after discontinuation and the possibility of symptom recurrence is reduced.

Colchicine poisoning treated with hemoperfusion and hemodialysis: A case report.

This case report described an improved case of colchicine poisoning using hemoperfusion and hemodialysis.

Risperidone Toxicity on Human Blood Lymphocytes in Nano molar Concentrations.

Risperidone is an atypical antipsychotic drug used for the pharmacotherapy of psychiatric disorders. Some reports indicate that risperidone is toxic to various systems of the body, including the immune system. This study evaluated the toxicity effect of risperidone on human blood lymphocytes. To achieve this aim, lymphocytes were isolated using Ficoll paque plus. The results showed that risperidone (12, 24 and 48 nM) causes toxicity in human blood lymphocytes by increasing the level of intracellular reactive oxygen species (ROS), damage to lysosomal membrane, the collapse of the mitochondrial membrane potential (MMP), and increased extracellular oxidized glutathione (GSSG). Also, exposure of human blood lymphocytes to risperidone is associated with a decrease in intracellular glutathione (GSH) levels. Finally, it could be concluded that oxidative stress is one of the mechanisms of risperidone-induced toxicity in human blood lymphocytes.

Differences in sensitivity of human lymphocytes and fish lymphocytes to polyvinyl chloride microplastic toxicity.

Polyvinyl chloride (PVC) microplastics are emerging contaminants affecting biological wastewater treatment processes. So far, the toxicological investigation of PVC microplastics usually focused on the anaerobic and denitrifying bacteria. It seems that the primary lymphocytes isolated from peripheral blood are more sensitive than most other organ cell types in vitro; therefore, the aim of this study was to assess the cytotoxicity of PVC microplastic on human and fish blood lymphocytes as a useful ex vivo model for accelerated human toxicity studies. Using biochemical analyses, we showed human lymphocytes are more sensitive to toxic effects of PVC microplastic than fish lymphocytes. Our result showed that addition of PVC microplastic at 24, 48, and 96 µg/ml for 3 h to human blood lymphocytes induced cytotoxicity. The PVC microplastic-induced cytotoxicity on human blood lymphocytes was associated with intracellular reactive oxygen species (ROS) formation, lysosomal membrane injury, mitochondrial membrane potential (MMP) collapse, depletion of glutathione, and lipid peroxidation. According to our results, PVC microplastic particles induce oxidative stress and organelle damage in human lymphocytes, while these significant alterations in toxicity parameters in PVC microplastic-treated fish lymphocytes were not observed. Finally, our findings suggest that human lymphocytes are more sensitive to PVC microplastic toxicity compared with fish lymphocytes.

Selective Toxicity Effect of Fatty Acids Omega-3, 6 and 9 Combination on Glioblastoma Neurons through their Mitochondria.

Glioblastoma (GBM) is one of the most common malignant tumors of the central nervous system that occurs in the brain and is a deadly disease. Despite the different approaches to the treatment of this malignancy, the discovery of new compounds with anti-cancer effects seems necessary. In this study, the selective toxicity effects of omega 3, 6 and 9 combinations on mitochondria isolated from U87MG human glioma cells and also human embryonic kidney 293 cells (HEK293) as normal control were investigated. The results indicated that the omega 3, 6 and 9 combinations significantly reduced succinate dehydrogenase (SDH) activity only in mitochondria isolated from U87MG human glioma cells. Additionally, exposure of mitochondria isolated from U87MG human glioma cells to this combination was associated with a selective increase in the level of reactive oxygen species (ROS), the collapse of the mitochondrial membrane potential (MMP), mitochondrial swelling and cytochrome c release. However, these effects were not observed in mitochondria isolated from HEK293 cells (as a normal group). According to results, it is proposed that the combination of omega 3, 6 and 9 could induce toxicity in U87MG human glioma cells through their mitochondria. This combination can be helpful as a complementary therapy in patients with GBM.

Organ Procurement From Poisoned Patients: A 14-Year Survey in 2 Academic Centers.

OBJECTIVES: Organ transplant from poisoned donors is an issue that has received much attention, especially over the past decade. Unfortunately, there are still opponents to this issue who emphasize that toxins and drugs affect the body's organs and do not consider organs from poisoned donors appropriate for transplantation. MATERIALS AND METHODS: Cases of brain death due to poisoning were collected from 2 academic centers in Tehran, Iran during a period from 2006 to 2020. Donor information and recipient condition at 1 month and 12 months after transplant and the subsequent transplant success rates were investigated. RESULTS: From 102 poisoned donors, most were 30 to 40 years old (33.4%) and most were men (55.9%). The most common causes of poisoning among donors were opioids (28.4%). Six candidate donors had been referred with cardiorespiratory arrest; these patients had organs that were in suitable condition, and transplant was successful. Acute kidney injury was seen in 30 donors, with emergency dialysis performed in 23 cases. For 51% of donors, cardiopulmonary resuscitation was performed. The most donated organs were the liver (81.4%), left kidney (81.4%), and right kidney (80.4%). Survival rate of recipients at 1 month and 12 months was 92.5% and 91.4%, respectively. Graft rejection rate at 1 month and 12 months after transplant was 0.7% and 2.21%, respectively. CONCLUSIONS: Organ donation from poisoning-related brain deaths is one of the best sources of organ supply for people in need. If the organ is in optimal condition before transplant, there are no exclusions for use of the graft.

Toxicity effect of sesquiterpene lactones from Jurinea gabrieliae bornm on mitochondria isolated from U87 cells.

Sesquiterpene lactones (SLs) are a typical group of secondary metabolites in asteraceae family and well-known for their biologically potential in treatment of various diseases such as cancer and inflammation. Glioblastoma (GBM) is a most common brain malignancy in adults with poor prognosis. Finding phytochemicals with potential targeting mitochondria has been suggested as an important approach for many malignancies. In this study, we purified three guaianolide-type SLs, including 8-deacyloxy-8α-(methylacryloxy)-subluteolide (A), subluteolide (B) and janerin (C) from Jurinea gabrieliae Bornm by chromatography methods. Then, mitochondrial toxicity parameters were evaluated. All three SLs selectively inhibited SDH activity in mitochondria from U87 cells but not mitochondria from normal rat brain. In addition these SLs increased ROS formation and cytochrome c release and MMP collapse only in mitochondria from U87 cells but not normal rat neurons. Our results suggest that all three SLs may act as potential agents for future development in anti-glioma therapy.

Anti-Glioma Effect of Pseudosynanceia melanostigma Venom on Isolated Mitochondria from Glioblastoma Cells

Background: Glioblastoma is the most common primary malignant tumor of the central nervous system that occurs in the spinal cord or brain. Pseudosynanceia melanostigma is a venomous stonefish in the Persian Gulf, which our knowledge about is little. This study's goal is to investigate the toxicity of stonefish crude venom on mitochondria isolated from U87 cells. Methods: In the first stage, we extracted venom stonefish and then isolated mitochondria have exposed to different concentrations of venom. Finally, mitochondrial toxicity parameters (Succinate dehydrogenase (SDH) activity, Reactive oxygen species (ROS), cytochrome c release, Mitochondrial Membrane Potential (MMP), and mitochondrial swelling) have evaluated. Results: To determine mitochondrial parameters, we used 115, 230, and 460 µg/ml concentrations. The results of our study show that the venom of stonefish selectively increases upstream parameters of apoptosis such as mitochondrial swelling, cytochrome c release, MMP collapse and ROS. Conclusion: This study suggests that Pseudosynanceia melanostigma crude venom has selectively caused toxicity by increasing active mitochondrial oxygen radicals. This venom could potentially be a candidate for the treatment of glioblastoma.

Concurrent Inflammation Augments Antimalarial Drugs-Induced Liver Injury in Rats.

Purpose: Accumulating evidence suggests that drug exposure during a modest inflammation induced by bacterial lipopolysaccharide (LPS) might increase the risk of drug-induced liver injury. The current investigation was designed to test if antimalarial drugs hepatotoxicity is augmented in LPS­treated animals. Methods: Rats were pre-treated with LPS (100 µg/kg, i.p). Afterward, non-hepatotoxic doses of amodiaquine (25, 50 and 100 mg/kg, oral) and chloroquine (25, 50 and 100 mg/kg, oral) were administered. Results: Interestingly, liver injury was evident only in animals treated with both drug and LPS as estimated by pathological changes in serum biochemistry (ALT, AST, LDH, and TNF-α), and liver tissue (severe hepatitis, endotheliitis, and sinusoidal congestion). An increase in liver myeloperoxidase enzyme activity, lipid peroxidation, and protein carbonylation, along with tissue glutathione depletion were also detected in LPS and drug co-treated animals. Conclusion: Antimalarial drugs rendered hepatotoxic in animals undergoing a modest inflammation. These results indicate a synergistic liver injury from co-exposure to antimalarial drugs and inflammation.