Human & Experimental Toxicology最新文献

{"title":"An artificial intelligence algorithm for analyzing globus pallidus necrosis after carbon monoxide intoxication.","authors":"Ming-Jen Chan,&nbsp;Ching-Chih Hu,&nbsp;Wen-Hung Huang,&nbsp;Ching-Wei Hsu,&nbsp;Tzung-Hai Yen,&nbsp;Cheng-Hao Weng","doi":"10.1177/09603271231190906","DOIUrl":"10.1177/09603271231190906","url":null,"abstract":"<p><p>Globus pallidus necrosis (GPN) is one of typical neurological imaging features in patients with carbon monoxide (CO) poisoning. Current clinical guideline recommends neurological imaging examination for CO-intoxicated patients with conscious disturbance rather than routine screening, which may lead to undiagnosed GPN. We aimed to develop an artificial intelligence algorithm for predicting GPN in CO intoxication patients. We included CO intoxication patients with neurological images between 2000 and 2019 in Chang Gung Memorial Hospital. We collected 41 clinical and laboratory parameters on the first day of admission for algorithm development. We used fivefold cross validation and applied several machine learning algorithms. Random forest classifier (RFC) provided the best predictive performance in our cohort. Among the 261 patients with CO intoxication, 52 patients presented with GPN. The artificial intelligence algorithm using the RFC-based AI model achieved an accuracy = 79.2 ± 2.6%, sensitivity = 77.7%, precision score = 81.9 ± 3.4%, and F1 score = 73.2 ± 1.8%. The area under receiver operating characteristic was approximately 0.64. Top five weighted variables were Platelet count, carboxyhemoglobin, Glasgow Coma scale, creatinine, and hemoglobin. Our RFC-based algorithm is the first to predict GPN in patients with CO intoxication and provides fair predictive ability. Further studies are needed to validate our findings.</p>","PeriodicalId":13181,"journal":{"name":"Human & Experimental Toxicology","volume":"42 ","pages":"9603271231190906"},"PeriodicalIF":2.8,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10247876","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparing the effectiveness of L-carnitine and paraffin oil in acute aluminum phosphide poisoning using predictive biomarkers and scores: A randomized controlled clinical trial.","authors":"Walaa G Abdelhamid,&nbsp;Mahmoud L Sakr,&nbsp;Olfat E Mostafa,&nbsp;Dalia Zaafar,&nbsp;Hanan M Abdelwahab","doi":"10.1177/09603271221149650","DOIUrl":"10.1177/09603271221149650","url":null,"abstract":"<p><p>Aluminum phosphide (AlP) poisoning is a serious medical emergency with a high mortality rate. The absence of an exact antidote for AlP poisoning necessitates the quest for alternative treatment options. The study sought to assess the efficacy of adding L-carnitine or medicated paraffin oil to the conventional approach of treatment employed in cases of acute AlP poisoning. We conducted a 1 year, randomized, controlled, parallel-group, single-blind clinical study. 96 individuals with acute AlP poisoning were randomly assigned to one of three groups. The standard AlP therapy was administered to all groups according to the Poison Control Center guidelines at the Ain-Shams University hospitals. All patients underwent a medical history review, clinical examination, and laboratory tests. The outcomes were assessed. The participants in the study groups had mean ages ranging from 25.6 to 26.3 years. The cases analyzed were evenly distributed between genders, with the majority originating from rural areas. The average delay time varied from 2.9 to 4.2 h. All patients in the study reported ingesting AlP during suicide attempts. 12 hours after admission, many clinical and biochemical data improved in both intervention groups including cytochrome c oxidase, caspase-3, caspase-9, catalase, and superoxide dismutase. The intervention groups required significantly less mechanical ventilation and had a lower mortality rate than the control group. Decontamination with paraffin oil could be advantageous for reducing the severity of AlP poisoning, improving prognosis, and lowering the mortality rate.</p>","PeriodicalId":13181,"journal":{"name":"Human & Experimental Toxicology","volume":"42 ","pages":"9603271221149650"},"PeriodicalIF":2.8,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10480583","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hyperglycemia-induced endothelial exosomes trigger trophoblast dysregulation and abnormal placentation through PUM2-mediated repression of SOX2.","authors":"Aibing Zhu,&nbsp;Suwan Qi,&nbsp;Wenjuan Li,&nbsp;Dashu Chen,&nbsp;Xiaomin Zheng,&nbsp;Jianjuan Xu,&nbsp;Yaling Feng","doi":"10.1177/09603271221149656","DOIUrl":"https://doi.org/10.1177/09603271221149656","url":null,"abstract":"<p><strong>Background: </strong>Hyperglycemia is closely related to adverse pregnancy outcomes including pre-eclampsia (PE), a life-threatening complication with a substantial morbidity and mortality. However, the pathogenesis of abnormal placentation in gestational diabetes mellitus (GDM)-associated PE remains elusive.</p><p><strong>Method: </strong>Here we isolated exosomes from the human umbilical vein endothelial cells (HUVECs) treated with normal level of glucose (NG) and high levels of glucose (HG). The exosomes were added to HTR-8a/SVneo cells, a trophoblast cell line. High-throughput RNA-sequencing was performed to analyzed the changed RNAs in the exosomes and exosome-treated HTR-8a/SVneo cells. HTR-8a/SVneo cell phenotypes were evaluated from the aspects of cell proliferation, cell invasion and DNA damage.</p><p><strong>Results: </strong>After treatment with HG, the changed RNAs in exosomes was enriched in RNA stabilization and oxidative stress. The altered RNAs in the HTR-8a/SVneo cells treated with exosomes from HG-induced HUVECs were enriched in pathways related to cell adhesion, migration, DNA damage response and angiogenesis. The HG-induced exosomes impaired the proliferation and invasion of HTR-8a cells and caused the DNA damage. HG up-regulated PUM2 in the exosomes and exosome-treated HTR-8a/SVneo cells. PUM2 interacted with SOX2 mRNA, resulting in the mRNA degradation. Overexpression of SOX2 prevented the damage to HTR-8a/SVneo cells caused by the exosomes from HG-induced HUVECs.</p><p><strong>Conclusions: </strong>We demonstrate that high glucose-induced endothelial exosomes mediate abnormal phenotypes of trophoblasts through PUM2-mediated repression of SOX2. Our results reveal a novel regulatory mechanism of hyperglycemia in development of abnormal placentation and provide potential targets for preventing adverse pregnancy outcomes.</p>","PeriodicalId":13181,"journal":{"name":"Human & Experimental Toxicology","volume":"42 ","pages":"9603271221149656"},"PeriodicalIF":2.8,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10501112","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mitochondrial ROS induced by ML385, an Nrf2 inhibitor aggravates the ferroptosis induced by RSL3 in human lung epithelial BEAS-2B cells.","authors":"Indra Putra Taufani,&nbsp;Jiro Hasegawa Situmorang,&nbsp;Rifki Febriansah,&nbsp;Sri Tasminatun,&nbsp;Sunarno Sunarno,&nbsp;Liang-Yo Yang,&nbsp;Yi-Ting Chiang,&nbsp;Chih-Yang Huang","doi":"10.1177/09603271221149663","DOIUrl":"https://doi.org/10.1177/09603271221149663","url":null,"abstract":"<p><p>Ferroptosis is a new type of cell death marked by iron and lipid ROS accumulation. GPX4 is one of the glutathione peroxidases known to regulate ferroptosis tightly. On the other hand, Nrf2 also plays a vital role in ferroptosis as it targets genes related to oxidant defense. Herein, we employed beas-2 human epithelial cells treated with a low concentration of RSL3 to induce ferroptosis. To study the protective role of Nrf2, we used ML385 as its specific inhibitor. A combination of ML385 and a low concentration of RSL3 synergistically induced more toxicity to RSL3. Furthermore, we found that mitochondrial ROS is elevated in ML385 and RSL3 combination group. In addition, Mito TEMPOL application successfully prevents the upregulation of mitochondrial ROS, lipid ROS, reduces the toxicity of RSL3, restores the antioxidant capacity of the cells, and mitochondrial functions reflected by mitochondrial membrane potential and mitochondrial oxidative phosphorylation system (OXPHOS) expression. Altogether, our study demonstrated that Nrf2 inhibition by ML385 induces more toxicity when combined with RSL3 through the elevation of mitochondrial ROS and disruption of mitochondrial function.</p>","PeriodicalId":13181,"journal":{"name":"Human & Experimental Toxicology","volume":"42 ","pages":"9603271221149663"},"PeriodicalIF":2.8,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10569790","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Acrylamide-induced meiotic arrest of spermatocytes in adolescent mice by triggering excessive DNA strand breaks: Potential therapeutic effects of resveratrol.","authors":"Y Gao,&nbsp;D Zhang,&nbsp;P Wang,&nbsp;X Qu,&nbsp;J Xu,&nbsp;Y Yu,&nbsp;X Zhou","doi":"10.1177/09603271231188293","DOIUrl":"10.1177/09603271231188293","url":null,"abstract":"<p><p><b>Background:</b> Baked carbohydrate-rich foods are the main source of acrylamide (AA) in the general population and are widely consumed by teenagers. Considering the crucial development of the reproductive system during puberty, the health risks posed by AA in adolescent males have raised public concern.<b>Methods:</b> In this study, we exposed 3-week-old male pubertal mice to AA for 4 weeks to evaluate its effect on spermatogenesis using computer-assisted sperm analysis (CASA) and historical analysis. Flow cytometric analysis and meiocyte spreading assay were conducted to assess meiosis in mice. The expression of meiosis-related proteins and double-strand break (DSB) proteins were evaluated by immunoblot analyses. Additionally, isolated spermatocytes were used to explore the role of resveratrol in AA-induced damages of meiosis.<b>Results:</b> Our results showed that AA decreased the testicular and epididymal indexes, reduced sperm count and motility, and induced morphological disruption of the testes in pubertal mice. Subsequent meiotic analysis revealed that AA increased the proportion of 4C spermatocytes and decreased the proportion of 1C spermatids. The expression levels of meiosis-related proteins (SYCP3, Cyclin A1 and CDK2) were downregulated, and signaling proteins (γH2AX, p-CHK2 and p-ATM) expression levels were upregulated in AA-treated mice testes. Similar expression patterns were observed in primary spermatocytes treated with AA and these effects were reversed significantly by resveratrol.<b>Conclusions:</b> Our results indicate that AA induces meiotic arrest via persistent activation of DSBs, which may contribute to AA-compromised spermatogenesis. Resveratrol could serve as a potential therapeutic agent against AA-induced meiotic toxicity. These data highlight the importance of natural product supplementation for treating AA-related reproductive toxicity.</p>","PeriodicalId":13181,"journal":{"name":"Human & Experimental Toxicology","volume":"42 ","pages":"9603271231188293"},"PeriodicalIF":2.8,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9945329","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Water-soluble Yb³⁺, Er³⁺ codoped NaYF₄ nanoparticles induced SGC-7901 cell apoptosis through mitochondrial dysfunction and ROS-mediated ER stress.","authors":"Chen Liu,&nbsp;Shaoqiang Sun,&nbsp;Jingwei Mao","doi":"10.1177/09603271231188493","DOIUrl":"https://doi.org/10.1177/09603271231188493","url":null,"abstract":"<p><strong>Background: </strong>Nanoparticles are potential luminescent probes; among them, upconversion nanoparticles (UCNP) are currently being developed as fluorescent probes for biomedical applications. However, the molecular mechanisms of UCNP in human gastric cell lines remain poorly understood. Here, we aimed to examine UCNP cytotoxicity to SGC-7901 cells and explore its underlying mechanisms.</p><p><strong>Methods: </strong>The effects of 50-400 μg/mL UCNP on human gastric adenocarcinoma (SGC-7901) cells were investigated. Flow cytometry was used to evaluate reactive oxygen species (ROS), mitochondrial membrane potential (ΔΨm), intracellular Ca²⁺ levels, and apoptosis. Activated caspase-3 and nine activities were measured; meanwhile, cytochrome C (Cyt C) in the cytosol and B-cell lymphoma 2 (Bcl-2), Bcl-2 associated X protein (Bax), protein kinase B (Akt), phosphorylated-Akt (p-Akt), 78 kDa glucose-regulated protein (GRP78), 94 kDa glucose-regulated protein (GRP94), calpain-1, and calpain-2 protein levels were also detected.</p><p><strong>Results: </strong>UCNP inhibited the viability of SGC-7901 cells in a concentration- and time-dependent manner and increased the proportion of cell apoptosis. Exposure to UCNP enhanced the ratio of Bax/Bcl-2, elevated the level of ROS, decreased ΔΨm, increased intracellular Ca²⁺ and Cyt C protein levels, decreased the levels of phosphorylated Akt, increased the activity of caspase-3 and caspase-9, and upregulated the protein expression of GRP-78, GRP-94, calpain-1 and calpain-2 in SGC-7901 cells.</p><p><strong>Conclusion: </strong>UCNP induced SGC-7901 cell apoptosis by promoting mitochondrial dysfunction and ROS-mediated endoplasmic reticulum (ER) stress, initiating the caspase-9/caspase-3 cascade.</p>","PeriodicalId":13181,"journal":{"name":"Human & Experimental Toxicology","volume":"42 ","pages":"9603271231188493"},"PeriodicalIF":2.8,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9797644","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rhamnetin alleviates polystyrene microplastics-induced testicular damage by restoring biochemical, steroidogenic, hormonal, apoptotic, inflammatory, spermatogenic and histological profile in male albino rats.","authors":"Ali Hamza,&nbsp;Muhammad Umar Ijaz,&nbsp;Haseeb Anwar","doi":"10.1177/09603271231173378","DOIUrl":"https://doi.org/10.1177/09603271231173378","url":null,"abstract":"<p><p>The current research was performed to evaluate the ameliorative effects of Rhamnetin (RHM) on polystyrene microplastics (PS-MPs)-instigated testicular dysfunction in male albino rats. 48 albino rats were distributed in four groups, i.e., control, PS-MPs treated, PS-MPs + RHM co-treated and RHM only supplemented group. PS-MPs exposure considerably reduced anti-oxidant enzymes i.e., catalase (CAT), glutathione peroxidase (GSR), superoxide dismutase (SOD) and glutathione reductase (GPx) activities. Whereas, reactive oxygen species (ROS) level along with malondialdehyde (MDA) was considerably escalated in PS-MPs treated rats as well as a potential decline was observed in sperm progressive motility. Additionally, a substantial upsurge was noticed in the count of dead sperms, deformity in the tail, mid-piece and head of sperms in PS-MPs treated rats. PS-MPs exposure also decreased steroidogenic enzymes, 17β-hydroxysteroid dehydrogenase (17β-HSD), steroidogenic acute regulatory protein (StAR) and 3β-hydroxysteroid dehydrogenase (3β-HSD) expressions. Moreover, the levels of inflammatory indices i.e., Interleukin-6 (IL-6), Nuclear factor kappa-B (NF-κB), Interleukin-1β (IL-1β), tumour necrosis factor-α (TNF-α) and cyclooxygenase-2 (COX-2) activity were also increased in PS-MPs administrated group. Besides it increased the expression of apoptotic markers (Bax and caspase-3) expression. Whereas, anti-apoptotic marker i.e., Bcl-2 expression was reduced. Moreover, luteinizing hormone (LH), follicle-stimulating hormone (FSH) as well as plasma testosterone levels were also decreased. PS-MPs exposure also led to a substantial histopathological damage in testicular tissues. However, RHM supplementation potentially reduced the damaging effects of PS-MPs in the reproductive tissues of male albino rats. Thus, the current study revealed, RHM possesses potential to prevent PS-MPs-induced testicular damage due to its anti-oxidant anti-apoptotic, anti-inflammatory as well as androgenic properties.</p>","PeriodicalId":13181,"journal":{"name":"Human & Experimental Toxicology","volume":"42 ","pages":"9603271231173378"},"PeriodicalIF":2.8,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9760788","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long noncoding RNA long intergenic non-protein-coding RNA 173 contributes to nasopharyngeal carcinoma progression by regulating microRNA-765/Gremlin 1 pathway.","authors":"Dan Wang,&nbsp;Heng Jiang","doi":"10.1177/09603271231172921","DOIUrl":"https://doi.org/10.1177/09603271231172921","url":null,"abstract":"<p><strong>Background: </strong>Long intergenic non-protein-coding RNA 173 (LINC00173) executes vital functions in various cancers. Nevertheless, its role and expression in nasopharyngeal carcinoma (NPC) have yet to be investigated. Here, we investigated its effects on the malignancy characteristics of NPC and elucidated the potential molecular mechanism of LINC00173 in NPC progression.</p><p><strong>Methods: </strong>Quantitative real-time reverse transcription-PCR (qRT-PCR) and immunoblotting were conducted to estimate the LINC00173, microRNA-765 (miR-765), and Gremlin 1 (GREM1) expressions in NPC cells and tissues. Cell counting kit-8 (CCK8), colony formation, and wound healing experiments were done to evaluate the proliferation, growth, and migration of NPC cells, respectively. The tumorous growth of NPC cells in vivo was assessed through the xenograft tumor experiment. Furthermore, the interactions among miR-765, LINC00173, and GREM1 were investigated through bioinformatics analyses, luciferase reporter and RNA immunoprecipitation chip assays.</p><p><strong>Results: </strong>An upregulated LINC00173 expression was found in NPC cell lines and tissues. The functional experiments uncovered that its downregulation repressed NPC cell proliferation, growth, and migration. In addition, LINC00173 knockdown hampered the NPC cells' tumorous growth in vivo. These effects could partially be reversed by downregulating miR-765. GREM1 is a downstream target of miR-765. GREM1 knockdown could repress the proliferation, growth, and migration of NPC cells. Nonetheless, these anti-tumor effects could be abolished by miR-765 downregulation. Mechanistically, LINC00173 increased the expression of GREM1 by binding with miR-765.</p><p><strong>Conclusions: </strong>LINC00173 functions as an oncogenic factor by binding with miR-765 to promote the progression of NPC via GREM1 upregulation. This study provides a novel insight into the molecular mechanisms involved in NPC progression.</p>","PeriodicalId":13181,"journal":{"name":"Human & Experimental Toxicology","volume":"42 ","pages":"9603271231172921"},"PeriodicalIF":2.8,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9811002","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sulforaphane triggers iron overload-mediated ferroptosis in gastric carcinoma cells by activating the PI3K/IRP2/DMT1 pathway.","authors":"Jing Wen,&nbsp;Fan Yang,&nbsp;Cheng-Xiang Fang,&nbsp;Hong-Liu Chen,&nbsp;Li Yang","doi":"10.1177/09603271231177295","DOIUrl":"10.1177/09603271231177295","url":null,"abstract":"<p><strong>Objective: </strong>Increasing evidence indicates that prolonged exposure to sulforaphane (SFN) can improve malignancies. However, the role of iron in SFN-triggered death in gastric carcinoma cells and the underlying molecular mechanisms remain unclear. Thus, the current study explored the effects of SFN on iron overload-mediated ferroptosis and the PI3K/IRP2/DMT1 pathway in gastric carcinoma cells.</p><p><strong>Methods: </strong>We utilized the MGC-803 cell line to assess whether SFN affected iron metabolism and whether this effect contributed to cell death. Pharmacological inhibition of iron metabolism also was performed to determine the molecular mechanism underlying SFN-triggered iron overload and the disturbance in iron metabolism.</p><p><strong>Results: </strong>Our data revealed that SFN treatment altered iron homeostasis and led to iron overload <i>in vitro</i>. Interestingly, SFN-stimulated cell death resulted from ferroptosis, a recently identified iron-dependent form of regulated cell death. Furthermore, an iron chelator, deferiprone, ameliorated the SFN-triggered mitochondrial dysfunction and reduced the iron overload. In addition, we found that the SFN-triggered iron overload was regulated by the PI3K/IRP2/DMT1 signaling pathway.</p><p><strong>Conclusion: </strong>We discovered that disturbance in iron metabolism might be involved in the SFN-triggered cell death in gastric carcinoma cells. Blockade of the PI3K/IRP2/DMT1 axis could provide a feedback effect on SFN-induced ferroptosis to protect tumor cells from growth.</p>","PeriodicalId":13181,"journal":{"name":"Human & Experimental Toxicology","volume":"42 ","pages":"9603271231177295"},"PeriodicalIF":2.8,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9851283","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development and validation of a risk prediction nomogram for disposition of acute clozapine intoxicated patients to intensive care unit.","authors":"Asmaa F Sharif,&nbsp;H A Aouissi,&nbsp;Zeinab A Kasemy,&nbsp;H Byeon,&nbsp;Heba I Lashin","doi":"10.1177/09603271231186154","DOIUrl":"https://doi.org/10.1177/09603271231186154","url":null,"abstract":"<p><strong>Background: </strong>Clozapine is an atypical antipsychotic drug used for the treatment of refractory schizophrenia. It is reported as the most toxic in its class. Using serum clozapine level as a severity indicator is doubtful and unfeasible, particularly in low resourced countries.</p><p><strong>Methods: </strong>This is an extended two-phase retrospective study that utilized medical records of patients diagnosed with acute clozapine intoxication and admitted to Tanta University Poison Control Center, Egypt during the past 6 years. Two hundred and eight medical records were used to establish and validate a nomogram for predicting the need for intensive care unit (ICU) admission in acute clozapine intoxicated patients.</p><p><strong>Results: </strong>A reliable simple bedside nomogram was developed and proved its significant ability to predict the need for ICU admission, with an area under the curve (AUC) of 83.9% and 80.8% accuracy. It encompassed the age of admitted patients (AUC = 64.8%, <i>p</i> = .003), respiratory rate (AUC = 74.7%, <i>p</i> < .001), O₂ saturation (AUC = 71.7%, <i>p</i> < .001), and random blood glucose level upon admission (AUC = 70.5%, <i>p</i> < .001). External validation of the proposed nomogram showed a high AUC (99.2%) with an overall accuracy of 96.2%.</p><p><strong>Conclusion: </strong>There is a need to develop a reliable objective tool predicting the severity and need for ICU admission in acute clozapine intoxication. The proposed nomogram is a substantially valuable tool to estimate ICU admission probabilities among patients with acute clozapine intoxication and will help clinical toxicologists make rapid decisions for ICU admission, especially in countries with low resources.</p>","PeriodicalId":13181,"journal":{"name":"Human & Experimental Toxicology","volume":"42 ","pages":"9603271231186154"},"PeriodicalIF":2.8,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10074280","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}