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ABSTRACT Objective: To report a pediatric case of drug-induced thrombotic microangiopathy caused by cocaine Case description: We report a nine-month-old patient who developed thrombotic microangiopathies after extreme cocaine intoxication, multiple organ dysfunction syndrome with hemodynamic dysfunction, anuric renal failure, liver failure, encephalopathy, and myocardial injury, corresponding phenotypically to thrombocytopenia-associated multiple organ failure. The patient received continuous venous hemofiltration and therapeutic plasma exchange, recovering satisfactorily. She was discharged after 30 days of hospitalization under the guidance of the childcare service, and was healthy after one year of follow-up. Toxicological samples confirmed high levels of cocaine and derivatives in blood, urine and hair. Comments: To our knowledge, this is the first reported pediatric case. There are particularities of cocaine intoxication pathophysiology that can trigger thrombotic microangiopathies because of vasoconstriction, direct endothelial injury, platelet activation, and increasing von Willebrand factor and fibrinogen levels. All of which results in a prothrombotic state, inflammatory dysregulation, and microvascular thrombi. The increasing use of cocaine, especially among young adults, puts children at high risk of toxicity, either by passive unintentional exposure, or abuse due to the increased availability in homes.
RESUMO Objetivo: Relatar um caso pediátrico de microangiopatia trombótica induzida por drogas causada por cocaína Descrição do caso: Relatamos uma paciente de nove meses de idade que desenvolveu microangiopatia trombótica após intoxicação extrema por cocaína, síndrome de disfunção de múltiplos órgãos com disfunção hemodinâmica, insuficiência renal anúrica, insuficiência hepática, encefalopatia e lesão miocárdica, correspondendo fenotipicamente à falência múltipla de órgãos associada à trombocitopenia. A paciente recebeu hemofiltração venosa contínua e plasmaférese terapêutica, recuperando-se satisfatoriamente. Recebeu alta após 30 dias de internação sob orientação do serviço de puericultura e estava saudável após um ano de seguimento. Amostras toxicológicas confirmaram altos níveis de cocaína e derivados no sangue, urina e cabelos. Comentários: Até onde sabemos, este é o primeiro caso pediátrico relatado. Existem particularidades da fisiopatologia da intoxicação por cocaína que podem desencadear a microangiopatia trombótica devido à vasoconstrição, lesão endotelial direta, ativação plaquetária e aumento do fator de von Willebrand e dos níveis de fibrinogênio. Tudo isso resulta em um estado pró-trombótico, desregulação inflamatória e trombos microvasculares. O uso crescente de cocaína, principalmente entre adultos jovens, coloca as crianças em alto risco de toxicidade, seja por exposição passiva não intencional ou abuso devido à maior disponibilidade nas residências.
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Objetivo: Este trabalho tem como propósito fornecer uma análise abrangente das características clínicas, etiológicas, radiográficas e histopatológicas da osteonecrose dos maxilares relacionada ao uso de medicamentos, além de abordar os métodos de diagnóstico, prevenção e estratégias terapêuticas. Materiais e métodos: foi realizada uma busca por artigos científicos publicados no período de 2015 a 2023, utilizando as bases de dados Scientific Electronic Library Online (SciELO), US National Library of Medicine (PubMed) e ScienceDirect. Conclusão: Embora infrequente, há um considerável potencial de ocorrência de osteonecrose dos maxilares em pacientes submetidos a terapia prolongada com medicamentos antirreabsortivos e antiangiogênicos, especialmente quando não são adotadas medidas preventivas adequadas. A implementação de práticas preventivas, a vigilância das condições bucais e a colaboração de uma equipe multidisciplinar são fundamentais para reduzir os riscos associados a essa condição patológica.(AU)
Objective: This work aims to provide a comprehensive analysis of the clinical, etiological, radiographic and histopathological characteristics of Medication-Related Jaw Osteonecrosis, in addition to addressing diagnostic methods, prevention and therapeutic strategies. Materials and methods: A search was carried out for scientific articles published between 2015 and 2023, using the Scientific Electronic Library Online (SciELO), US National Library of Medicine (PubMed) and ScienceDirect databases. Conclusion: Although infrequent, there is a considerable potential for osteonecrosis of the jaw to occur in patients undergoing prolonged therapy with antiresorptive and antiangiogenic medications, especially when adequate preventive measures are not adopted. The implementation of preventive practices, surveillance of oral conditions and the collaboration of a multidisciplinary team are essential to reduce the risks associated with this pathological condition.(AU)
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Humans , Osteonecrosis/chemically induced , Osteonecrosis/therapy , Jaw Diseases/chemically induced , Jaw Diseases/therapy , Risk Factors , Angiogenesis Inhibitors/adverse effects , Bone Density Conservation Agents/adverse effects , Bisphosphonate-Associated Osteonecrosis of the Jaw/therapy , Denosumab/adverse effectsABSTRACT
Introducción: Los antipsicóticos son medicamentos que pueden producir elevaciones transitorias de las enzimas hepáticas. La clozapina es un antipsicótico atípico usado en el tratamiento de la esquizofrenia refractaria a los antipsicóticos convencionales y existe evidencia que puede producir elevaciones de las transaminasas hepáticas, expresión de dafño hepático con patrón hepatocelular. Métodos: Reporte de caso y revisión no sistemática de la literatura relevante. Presentación del caso: Una mujer de 39 años con diagnóstico de esquizofrenia paranoide acudió a un servicio de urgencias de un hospital general por náuseas, vómitos e ictericia que apareció tras el inicio de clozapina. No hubo mejoría clínica de la paciente durante la hospitalización, que falleció a los 44 días de su ingreso. Revisión de la literatura: La clozapina puede elevar las cifras de función hepática de manera transitoria y asintomática. Hay criterios clínicos para recomendar la suspensión de este antipsicótico. Conclusiones: Este caso es el tercero en la literatura que registra un desenlace fatal tras un cuadro de hepatotoxicidad inducido por clozapina. © 2021 Asociación Colombiana de Psiquiatría. Publicado por Elsevier España, S.L.U. Todos los derechos reservados.
Introduction: Antipsychotics are drugs that can produce transient elevations of hepatic enzymes. Clozapine is an atypical antipsychotic used in treatment-resistant schizophrenia and there is evidence that it can produce elevations of hepatic transaminases, expression of liver damage in a hepatocellular pattern. Methods: Case report and non-systematic review of the relevant literature. Case presentation: A 39-year-old woman with a diagnosis of paranoid schizophrenia attended the emergency department of a general hospital for nausea, vomiting and jaundice that appeared after the initiation of clozapine. There was no clinical improvement during hospitalization, and death occurred after 44 days. Literature review: Clozapine can increase the liver enzyme levels transiently and asymptomatically; however, there are clinical criteria that recommend the withdrawal of the antipsychotic. Conclusions: This is the third case reported in the literature of a fatal outcome of clozapine-induced hepatotoxicity.
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Abstract Introduction Alterations in upper airway flow dynamics and sites of airway obstruction immediately after tonsillectomy and adenoidectomy (TA) have not been assessed. Identification of the changes in airway obstruction patterns after TA potentially improves the surgical management of children with obstructive sleep apnea (OSA). Objectives To evaluate the effect of TA on upper airway obstruction patterns detected with drug-induced sleep endoscopy (DISE). Methods The medical records of patients who underwent pre-TA DISE during the induction of anesthesia and post-TA DISE at the end of TA were reviewed. Data pertaining to polysomnography and DISE findings were analyzed. Results Twenty-seven patients (15 male and 12 females aged between 2 and 18 years old) were identified. All patients had obstruction at multiple sites of the upper airway. Prior to TA, airway obstruction was at the level of the velum in 27 patients, of the oropharynx/lateral walls in 27, of the tongue in 7, and of the epiglottis in 4. After TA, airway obstruction was at the level of the velum in 24 patients, of the oropharynx/lateral walls in 16, of the tongue in 6, and of the epiglottis in 4. The degree of obstruction at the levels of the velum and oropharynx/lateral walls after TA was significantly decreased. Conclusions Drug-induced sleep endoscopy performed prior to TA revealed that most of the sites of airway obstruction persisted after TA in OSA children with multiple sites of airway obstruction. Further studies in larger group of children with OSA are needed to establish the value of DISE findings in predicting residual OSA after TA, surgical planning, determining the need for post TA sleep study, and counseling caregivers.
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Naproxen is a widely used nonsteroidal anti-inflammatory drug (NSAID) in pediatric population, used for mild-to-moderate pains, arthritis, and other immune-mediated disorders. It rarely causes clinically apparent liver injury in the adult population taking high doses of the drug over a prolonged period and is reported even rarer in pediatric population. We present a case of drug-induced liver injury (DILI) in a 13-year-old girl taking naproxen in therapeutic doses for juvenile rheumatoid arthritis. There was a complete recovery of liver function following discontinuation of naproxen therapy.
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Acetaminophen is a drug widely used in the world and easily accessible due to its antipyretic, analgesics characteristics, among others (1); however, exposure to toxic doses causes organic damage and even death. We present the case of an 18-year-old female patient who ingested 40 grams of acetaminophen and developed severe liver dysfunction, being treated with N-acetylcysteine (NAC) antidotal therapy according to the simplified scheme: Scottish and Newcastle Anti-emetic Pretreatment Paracetamol Poisoning Study Regimen (SNAP), presenting improvement in the clinical course and decrease in liver profiles, coagulation disorder, INR and resolution of the condition.
El acetaminofén es un fármaco ampliamente usado en el mundo y de fácil acceso por sus características antipiréticas, analgésicas, entre otras (1); sin embargo la exposición a dosis tóxicas produce daños a nivel orgánico e incluso la muerte. Presentamos el caso de una paciente mujer de 18 años que ingirió 40 gramos de acetaminofén y desarrolló injuria hepática severa, siendo tratada con terapia antidotal de N-acetilcisteína (NAC) según el esquema simplificado: Scottish and Newcastle Anti-Emetic Pretreatment Paracetamol Poisoning Study Regimen (SNAP), presentando mejoría del curso clínico y disminución de los perfiles hepáticos, trastorno de coagulación, INR y resolución del cuadro.
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ObjectiveTo explore and establish the liver injury risk prediction model of indirect toxicity of Chinese medicinals under the condition of compound formulas， and provide new ideas and methods for the study of evaluation of liver injury of Chinese medicinals based on indirect toxicity. MethodsTaking Buguzhi （Fructus Psoraleae） pre-parations as model drug， the combined Chinese medicinals with Buguzhi （Fructus Psoraleae） of high frequency are screened out， and their components and action targets were obtained through TCMSP， TCMIP and PharmMapper databases. The association strength value and risk value of Chinese medicinals that acted on the nuclear factor κB （NF-κB） pathway were analyzed. For those having greater values than the median association strength value and risk value were regarded as indirect Chinese medicinals of liver injury risk. In this way， a prediction model of liver injury risk of Chinese medicinals was constructed based on immune activation-related indirect liver injury process （taking NF-κB pathway as an example）. And verification of the prediction model was performed using Heshouwu （Radix Polygoni Multiflori） preparations. ResultsThe prediction model of liver injury risk based on important immunoactivated pathway （taking NF-κB pathway as an example） found that Yinyanghuo （Herba Epimedii） （association strength value = 0.18， risk value = 0.25） was a Chinese medicinal with potential risk of indirect liver injury within Buguzhi （Fructus Psoraleae） prepartions， which may increase the risk of liver injury by positively regulating Bruton's tyrosine kinase （Btk） and protein kinase C theta （PKCθ） on NF-κB pathway. Further verification of prediction model by Heshouwu （Radix Polygoni Multiflori） preparations showed that Buguzhi （Fructus Psoraleae） （association strength value = 0.25， risk value = 0.33） and Tusizi （Semen Cuscutae） （Semen Cuscutae， association strength value = 0.34， risk value = 0.33） may increase the liver injury risk of Heshouzu. ConclusionThe liver injury risk prediction model of indirect toxicity of Chinese medicinals has been constructed in this study， providing metho-dological reference for the identification of Chinese medicinals of indirect liver injury risk under the condition of compound formulas.
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Objective:To investigate the clinical characteristics of drug-induced liver injury and provide a theoretical basis for the prevention and treatment of drug-induced liver injury.Methods:The clinical data of 202 patients with complete information on drug-induced liver injury who received treatment in First Hospital of Shanxi Medical University from November 2018 to November 2021 were collected. The information including gender, age, type and name of drugs taken or exposed, clinical characteristics, autoantibodies, and liver function was statistically analyzed.Results:Among the 202 patients with drug-induced liver injury, 77 patients (38.1%) were male and 125 patients (61.9%) were female. Age distribution was mainly at > 40-60 years. There were 141 cases (69.8%) of hepatocellular type, 27 cases (13.4%) of cholestatic type, and 34 cases (16.8%) of mixed type. There were statistically significant differences in alanine aminotransferase, aspartate aminotransferase, γ-glutamine transferase, alkaline phosphatase, prothrombin time, international standardized ratio, and prothrombin activity between different clinical types ( H = 91.43, 58.65, 9.25, 32.69, 9.56, 8.19, 9.40, all P < 0.05). Among the 202 patients with drug-induced liver injury, severe liver injury occurred in the largest proportion of cases (40.6%). There was no significant difference in the disease severity between different clinical types ( P = 0.789). The top three types of drugs causing liver injury were traditional Chinese medicine [52.0% (105/202)], antineoplastic drugs [6.4% (13/202)], and antipsychotics [5.9% (12/202)]. The detection rate of autoantibodies in 202 patients with drug-induced liver injury was 29.7% (60/202). Conclusion:Drug-induced liver injury lacks specificity in clinical manifestations. A wide variety of drugs can cause liver injury. Clinicians should strengthen liver function monitoring in key populations. The proportion of patients with mixed-type liver failure is high, which should be taken seriously. When patients with drug-induced liver injury are positive for liver disease-related antibodies, clinicians should be vigilant about the possibility of drug-induced liver injury.
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Objective To investigate the clinical, biochemical, pathological, disease course, and prognostic features of drug-induced liver injury (DILI) patients with different types of bile duct injury. Methods Four patients who were diagnosed with bile duct injury-type DILI by liver biopsy in Shijiazhuang Fifth Hospital, from March 2015 to October 2010 were selected, and related data were collected, including clinical data, laboratory examinations, radiological examination, and prognosis.The semi-quantitative score was determined for liver pathological morphology, and each indicator was compared between the four patients. Results Bile duct injury-type DILI was more common in female patients, and most patients tended to have a good prognosis.Clinical symptoms, liver biochemical parameters, and prognosis varied with the site, grade, scope, regeneration, and repair of bile duct injury. Conclusion Liver biopsy is still the gold standard for making a definite diagnosis of bile duct injury-type DILI, understanding the condition of lesions, and judging the prognosis of this disease.
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Objective To investigate the clinical features of patients with drug-induced liver injury (DILI). Methods A retrospective analysis was performed for the clinical data of 1 376 patients with DILI who were admitted to 20 hospitals in Shaanxi Province, China, from 2009 to 2019 and were diagnosed with RUCAM scale as the diagnostic criteria, and these patients were analyzed in terms of sex, age, underlying diseases, suspected drugs causing DILI, clinical manifestations, laboratory examination, treatment process, and prognosis. The t -test and Wilcoxon test were used for comparison of continuous data between two groups, the chi-square test was used for comparison of categorical data between groups, and the Kruskal-Wallis H rank sum test was used for comparison of ordered polytomous data between groups. Results Among the 1 376 patients, there were 577(41.93%) male patients and 799 (58.07%) female patients, with a male/female ratio of 0.72:1. As for different age groups, the 40-60 years group had a higher incidence rate and accounted for 44.77%, and there was a significant difference in sex distribution between different age groups ( χ 2 =20.784, P =0.008). As for the three clinical types, there was no significant difference in incidence rate between men and women ( χ 2 =1.409, P =0.494), and there was a significant difference in the distribution of clinical types between different age groups ( χ 2 =47.025, P 0.05). Conclusion There is a high incidence rate of DILI in women and middle-aged and elderly people, and traditional Chinese medicine is the leading cause of DILI. Patients with different clinical types tend to have different prognoses, with a good overall prognosis.
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BackgroundIn order to implement the spirit of the 20th National Congress of the Communist Party of China， and the Opinions on Promoting the Inheritance， Innovation and Development of Traditional Chinese Medicine（TCM）， to regularly summarize the research results of TCM， to present the academic progress of TCM dynamically， and to give full play to the academic leadership of academic groups， the China Association of Chinese Medicine had organized the selection of the top 10 academic progress of TCM in 2022. The selection work adhered to the four orientations， eliminated the four only， highlighted the solution of clinical problems， answered scientific questions， led the development of the industry， reflected the exploratory and forward-looking， innovative and breakthrough， focused on new laws， new discoveries， new methods， new products， new theories in the field of basic research and applied basic research in TCM. After dynamic collection， preliminary examination， review and final judgment， the top 10 academic progress of TCM in 2022 were determined.
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Objective To investigate whether Toll-like receptor 4 (TLR4) inhibition affects liver regeneration during acetaminophen (APAP)-induced liver injury in mice, as well as the mechanism of TLR4 involved in liver regeneration. Methods A total of 78 male CD-1 mice were divided into nine groups using a random number table, i.e., three control groups (normal control group, solvent control group, inhibitor control group) with 6 mice in each group and six experimental groups (APAP 24-hour group, TAK-242+APAP 24-hour group, APAP 48-hour group, TAK-242+APAP 48-hour group, APAP 72-hour group, TAK-242+APAP 72-hour group) with 10 mice in each group. The mice in the experimental groups were given a single dose of intraperitoneally injected APAP (300 mg/kg), and TAK-242 was intraperitoneally injected at a dose of 3 mg/kg at 3 hours before APAP administration. Serum and liver tissue samples were collected at different time points. The biochemical method was used to measure the serum level of alanine aminotransferase (ALT); HE staining was used to observe liver pathological changes; RT-PCR, Western blot, and immunohistochemistry were used to measure the expression levels of Cyclin D1, PCNA, Ki-67, STAT3, and p-STAT3. The t -test was used for comparison of normally distributed continuous data between two groups; a one-way analysis of variance was used for comparison between multiple groups, and the least significant difference t -test was used for further comparison between two groups. The Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups, and the Kruskal-Wallis H test was used for comparison between multiple groups and further comparison between two groups. Results Compared with the normal control group, the APAP 24-hour and 48-hour groups had a significantly higher serum level of ALT (both P < 0.05), and the TAK-242+APAP 24-hour and 48-hour groups had a significantly higher serum level of ALT than the APAP group at the same time point (both P < 0.05). HE staining showed typical central lobular necrosis in the liver of APAP-treated mice, and the TAK-242+APAP 24-hour and 48-hour groups had a significantly larger necrotic area than the APAP group at the same time point (both P < 0.05). RT-PCR, Western blot, and immunohistochemistry showed that the TAK-242+APAP 24-hour, 48-hour, and 72-hour groups had significantly lower mRNA and protein expression levels of Cyclin D1 than the APAP group at the same time point (all P < 0.05); the TAK-242+APAP 24-hour, 48-hour, and 72-hour groups had a significantly lower mRNA expression level of PCNA than the APAP group at the same time point (all P < 0.05), and the TAK-242+APAP 24-hour and 48-hour groups had a significantly lower protein expression level of PCNA than the APAP group at the same time point (all P < 0.05); the TAK-242+APAP 24-hour and 72-hour groups had a significantly lower mRNA expression level of Ki-67 than the APAP group at the same time point (all P < 0.05), and the TAK-242+APAP 24-hour, 48-hour, and 72-hour groups had a significantly lower protein expression level of Ki-67 than the APAP group at the same time point (all P < 0.05). In addition, the TAK-242+APAP 24-hour and 48-hour groups had a significantly lower phosphorylation level of STAT3 than the APAP group at the same time point (both P < 0.05). Conclusion TLR4 may promote liver regeneration by increasing the phosphorylation level of STAT3 during APAP-induced liver injury in mice.
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Objective To investigate the value of total bilirubin rebound rate (TBRR), total bilirubin clearance rate (TBCR), and TBCR after 1 week of treatment (ΔTBCR) in evaluating the short-term prognosis of patients with severe drug-induced liver injury (DILI) after artificial liver support therapy. Methods A retrospective analysis was performed for 203 patients with severe DILI who received artificial liver support therapy in Tianjin Third Central Hospital from September 2013 to December 2021, and general information, biochemical parameters, and clinical classification were collected. The patients were divided into improved group and unhealed group according to the prognosis at discharge, and Model for End-Stage Liver Disease (MELD) score, TBRR, TBCR, and ΔTBCR were calculated. The independent samples t -test was used for comparison of normally distributed continuous data between groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between groups; the chi-square test was used for comparison of categorical data between groups. The receiver operating characteristic (ROC) curve was plotted to investigate the value of assessment indices in predicting the prognosis of patients, and the Kaplan-Meier method was used to investigate the difference in the length of hospital stay in the context of different assessment indices. Results Compared with the unhealed group, the improved group had significantly lower age ( t =-2.762, P < 0.05), white blood cell count ( Z =-3.184, P < 0.05), total bilirubin ( t =-2.809, P < 0.05), conjugated bilirubin ( t =-2.739, P < 0.05), international normalized ratio ( Z =-2.357, P < 0.05), MELD score ( t =-3.090, P < 0.05), and TBRR ( t =-4.749, P < 0.05), as well as significantly higher albumin ( t =2.198, P < 0.05), prothrombin time activity ( t =2.018, P < 0.05), TBCR ( t =2.166, P < 0.05), and ΔTBCR ( t =9.549, P < 0.05). MELD score, TBRR, TBCR, and ΔTBCR had an area under the ROC curve (AUC) of 0.656, 0.727, 0.611, and 0.879, respectively, and ΔTBCR had a better predictive value than TBRR ( Z =3.169, P =0.001 5). The optimal cut-off value was 22.5% for TBRR (with a sensitivity of 94.6% and a specificity of 45.2%) and 27.4% for ΔTBCR (with a sensitivity of 77.7% and a specificity of 86.5%). ΔTBCR showed a good predictive value in different clinicopathological types, with extremely high sensitivity (91.4%) and specificity (100.0%) in evaluating the treatment outcome of patients with mixed-type DILI after artificial liver support therapy. Conclusion TBRR and ΔTBCR have a higher value than MELD score in evaluating the short-term prognosis of patients with severe DILI after artificial liver support therapy, among which ΔTBCR has a higher predictive value.
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In recent years, the potential hepatotoxicity of green tea extract (GTE) has attracted more and more attention. With reference to the current studies on liver injury caused by GTE and the latest drug hepatotoxicity classification, this article systematically elaborates on the objectivity and causal mechanisms of liver injury caused by GTE. Based on the main risk factors for liver injury caused by GTE, this article also proposes recommendations for safe and rational use of such products, so as to provide valuable insights for in-depth research on the mechanism of liver injury caused by GTE and risk prevention and control, and meanwhile, it also provides an important reference for the therapeutic use of GTE to improve health conditions.
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With the approval and launch of a large number of new drugs, the incidence rate of drug-induced liver injury (DILI) is increasing year by year, which may affect the treatment of primary diseases. As an adverse drug reaction, DILI cannot be completely eliminated, and the clinical goal is to minimize its influence through prevention and control. This article reviews the research advances in the risk factors for DILI, the monitoring of DILI, and retreatment. Studies have shown that the risk of DILI can be increased by certain factors under some circumstances. Early identification of risk factors, rational monitoring, and focus on the timing and method for retreatment can reduce the development or progression of DILI and thus improve the prognosis of patients.
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ObjectiveTo explore the "efficacy-toxicity" association mechanisms of Tripterygium wilfordii polyglycoside tablets （TWPT） by establishing and analyzing an interaction network associated with the clinical efficacy of TWPT in the treatment of rheumatoid arthritis （RA） and TWPT-induced liver injury. MethodOn the basis of the TWPT efficacy-related gene expression profile and TWPT-induced liver injury-related protein expression profile which were both obtained from our clinical cohorts， the "efficacy-toxicity" association network of TWPT was constructed， and the key network targets were identified by calculating the topological values of the nodes， including the degree， closeness and betweenness. After that， the biological functions and pathways of the key network targets were investigated by enrichment analysis. ResultA total of 119 differentially expressed genes （58 up-regulated and 61 down-regulated） between RA patients with TWPT well and weak response were identified as TWPT efficacy-related genes by clinical transcriptomics， and 49 differentially expressed proteins （36 up-regulated and 13 down-regulated） were demonstrated to be TWPT-induced liver injury-related proteins by clinical proteomics. In addition， the clinical symptom enrichment analysis indicated that the TWPT efficacy-related genes were significantly associated with various clinical symptoms of arthralgia in traditional Chinese medicine and clinical phenotypes of modern medicine， and most of the TWPT-induced liver injury-related proteins were involved in digestive system abnormalities. Therefore， the aforementioned multi-omics data represented the main clinical symptoms of TWPT treating RA and inducing liver injury. Mechanically， the "efficacy-toxicity" association network revealed that both TWPT efficacy-related genes and TWPT-induced liver injury-related core proteins were involved in the "immune-inflammatory" imbalance， especially playing an important role in neutrophil degranulation， complement cascade reaction， and immune-inflammatory response mediated by protein post-translational modification. Notably， the above genes and proteins were also enriched in various signaling pathways related to cell proliferation and cell cycle regulation， such as RAS and mitogen-activated protein kinase （MAPK） signaling pathway， and in several liver functional processes， such as glycogen metabolism and redox reaction. ConclusionThis study systematically explained the "efficacy-toxicity" association characteristics and molecular mechanisms of TWPT by applying a research strategy integrating clinical phenomics， transcriptomics and proteomics， laying a good data foundation for exploring the "efficacy enhancing and toxicity-reducing" mechanisms of TWPT.
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OBJECTIVE To evaluate the rationality of epinephrine in the treatment of drug-induced anaphylactic shock， and to provide a reference for further standardizing the treatment measures of anaphylactic shock. METHODS According to the relevant data of the reports of severe adverse drug reaction （ADR） of drug-induced anaphylactic shock provided by Chongqing ADR Monitoring Center from 2015 to 2022， the selection of treatment drugs， and the application of epinephrine in anaphylactic shock were analyzed retrospectively； the clinical outcomes of anaphylactic shock with different epinephrine administration methods were investigated. RESULTS A total of 1 415 cases of severe ADR related to drug-induced anaphylactic shock were reported， with a male-to-female ratio of 1.04∶1； the drugs that caused allergic shock mainly included anti-infective drugs （47.92%）， TCM injections （9.12%）； the patients who suffered from drug-induced anaphylactic shock within 10 min after medication accounted for 43.96%； 97.24% of patients were cured or improved， and 2.76% of patients died or did not been improved. Among 1 415 patients， 63.39% of patients were treated with epinephrine， and the patients who preferred epinephrine treatment accounted for 53.14%； the intramuscular injection， subcutaneous injection， intravenous injection and intravenous drip accounted for 33.78%， 30.32%， 25.75% and 1.23%， respectively. The initial dose range of epinephrine was 0.01-10 mg， and the most frequent single dose was 1 mg （44.70%）. Excessive single doses of intramuscular injection， subcutaneous injection and intravenous injection accounted for 51.03% （148 cases）， 53.13% （136 cases） and 91.47% （193 cases） respectively， and the risk of overdose in intravenous injection was higher （P＜0.05）. The patients receiving initial treatment with epinephrine had a higher improvement rate/cure rate than those who did not use epinephrine （98.14% vs. 96.23%， P＝0.029）； the patients who preferred epinephrine had a higher improvement rate/cure rate than those who did not preferred epinephrine （98.14% vs. 95.17%， P＝0.031）； the improvement rate/cure rate of patients receiving intramuscular injection of epinephrine was higher than those without intramuscular injection （99.01% vs. 96.69%， P＝0.038）. CONCLUSIONS There are some unreasonable phenomena in the treatment of drug-induced anaphylactic shock， such as inappropriate selection of drugs， insufficient use of epinephrine， delay of administration， inappropriate route of administration and excessive single dose.
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Statins are a kind of prescription drug that is widely used to treat hyperlipidemia, coronary artery disease, and other atherosclerotic diseases. A common side effect of statin use is a mild rise in liver aminotransferases, which occurs in less than 3% of patients. Statin-related liver injury is most commonly caused by atorvastatin and simvastatin, but severe liver injury is uncommon. Therefore, understanding and evaluating hepatotoxicity and weighing the benefits and risks is of great significance to better realize the protective effect of statins.
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Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/adverse effects , Atorvastatin/adverse effects , Simvastatin/adverse effects , Chemical and Drug Induced Liver Injury/drug therapy , Drug-Related Side Effects and Adverse Reactions/drug therapyABSTRACT
Drug-induced liver injury (DILI) risk prediction, diagnosis establishment, clinical management, and all other aspects are facing great challenges. Although the current understanding of its pathogenesis is still incomplete, research over the past 20 years has shown that genetic susceptibility may play an important role in the occurrence and development of DILI. In recent years, pharmacogenomics studies have further revealed the association between human leukocyte antigen (HLA) genes, some non-HLA genes, and hepatotoxicity from certain drugs. However, due to the lack of well-designed, prospective, large-sample cohort validation and low positive predictive values, there may still be some way to go before the current results can be truly translated into clinical practice for precise prediction and prevention of DILI risk.
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Humans , Genetic Predisposition to Disease , Prospective Studies , Risk Factors , Chemical and Drug Induced Liver Injury/genetics , Drug-Related Side Effects and Adverse Reactions , LiverABSTRACT
Drug-induced liver injury (DILI) is one of the most common adverse drug reactions that may seriously threaten the health of children and is receiving increasing clinical attention day by day. There is still no independent diagnosis and treatment guideline for DILI in children, but its clinical features are not completely similar to those in adults. This article reviews the epidemiology, clinical features, diagnosis, and treatment progress in order to provide a reference for the management of DILI in children.