Correlation analysis of clinical indicators and liver failure-related prognostic score associated with prognosis in patients with amanita phalloides poisoning / 中华危重病急救医学

Objective:To analyze and compare the clinical indicators and the liver failure-related prognostic score of patients with amanita phalloides poisoning with different prognoses, and to explore potential prognostic indicators.Methods:A retrospective case-control study was conducted. The clinical data of 52 patients with amanita phalloides poisoning admitted to the department of emergency of Xijing Hospital Affiliated to Air Force Medical University from September 2016 to September 2021 were collected, including general information (gender, age), clinical indicators at admission [mean arterial pressure (MAP), total bilirubin (TBil), aspartate transaminase (AST), alanine transaminase (ALT), albumin (ALB), serum creatinine (SCr), blood urea nitrogen (BUN), creatine kinase (CK), D-dimer, fibrinogen degradation product (FDP), prothrombin time (PT), activated partial thromboplastin time (APTT), prothrombin activity (PTA), international normalized ratio (INR), white blood cell count (WBC), platelet count (PLT)], liver failure-related prognostic score [sequential organ failure assessment (SOFA), chronic liver failure (CLIF)-SOFA score, European Foundation for the Study of Chronic Liver Failure-organ failure (CLIF-C OF)], and 28-day outcome. The clinical indicators and liver failure-related prognostic scores of the patients with different prognoses were compared. Receiver operator characteristic curve (ROC curve) was used to determine the prognostic value of statistically significant indicators between different prognosis of patients with amanita poisoning.Results:A total of 45 patients were enrolled, of which 38 survived and 7 died within 28 days. The coagulation indicators including PT, APTT, INR, and liver failure-related prognostic scores including SOFA score, CLIF-SOFA score, and CLIF-C OF score in the patients of death group were significantly higher than those in the survival group [PT (s): 69.59±15.94 vs. 25.99±4.64, APTT (s): 83.44±17.82 vs. 42.64±3.79, INR: 6.13±1.47 vs. 2.07±0.33, SOFA score: 11.57±1.38 vs. 6.03±0.77, CLIF-SOFA score: 9.86±2.17 vs. 5.55±0.67, CLIF-C OF score: 11.71±0.97 vs. 8.37±0.35], and PLT was significantly lowered (×10 9/L: 80.57±29.65 vs. 169.60±11.80, all P < 0.05). ROC curves showed that coagulation indicators including PT, APTT, INR, PLT, and liver failure-related prognostic scores including SOFA score and CLIF-C OF score were associated with the prognosis of patients with amanita phalloides poisoning, with the area under the ROC curve (AUC) of > 0.75. The sensitivity of the clinical indicators was above 85%, and the AUC and specificity of INR were the highest, which were 0.88 [95% confidence interval (95% CI) was 0.74-1.00] and 83.0%, respectively; meanwhile, the sensitivity of the liver failure-related prognostic scores was 100%, and the AUC and specificity of the CLIF-C OF score were the highest, which were 0.86 (95% CI was 0.74-0.99) and 66.0%, respectively. Conclusion:INR and CLIF-C OF score can be used to evaluate the poor prognosis of patients with amanita phalloides poisoning.

Micetismo: reporte de dos casos fatales y revisión bibliográfica / Mycetism: Report of two fatal cases and review of the literature

Justificación:El micetismo es la intoxicación producida por la ingestión de setas silvestres, que puede presentarse clínicamente con diferentes síndromes toxicológicos, dependiendo de la especie de hongo involucrada y sus toxinas. Su importancia médicolegal radica en que la ingesta puede ocurrir de manera accidental, homicida o suicida. Objetivo: Revisar aspectos relevantes sobre el micetismo, para el reconocimiento de síndromes toxicológicos asociados a la ingesta de setas. Metodología:Se revisaron diferentes bases de datos utilizando las palabras clave: micetismo, Amanita phalloides, autopsia médicolegal, abordaje diagnóstico. Resultados:A. phalloides, contiene amatoxinas causantes de insuficiencia hepática aguda y las falotoxinas responsables de manifestaciones gastrointestinales 10 horas después de la ingesta, característica del síndrome tóxico faloidiano. Los casos que se describen corresponden a dos femeninas de la misma familia, una mujer adulta 36 años embarazada y su hija de seisaños, procedentes de una comunidad rural en la parte central de Honduras, que fallecieron después de la ingestión de setas silvestres y cuyas autopsias se realizaron en la Dirección de Medicina Forense de Tegucigalpa, para establecer la causa de muerte. En la historia médico legal se consignó que los hongos fueron cocinados por la madre y consumidos por ella y su hija. Conclusión:Es recomendable la capacitación continuade los médicos de emergencia en hospitales, para el reconocimiento de síndromes toxicológicos asociados a la ingesta de setas, con el propósito de tratar oportunamente estos pacientes y ofrecerles mejor oportunidad de sobrevivir...(AU)

Falla hepática aguda y otros trastornos causados por el consumo de amanita phalloides / Acute liver failure and other disorders caused by eating amanita phalloides

A pesar de ser una patología rara la intoxicación por hongos puede llegar a ser potencialmente mortal, principalmente si se habla del Amanita phalloides, el cual contiene toxinas capaces de producir alteraciones gastrointestinales y falla hepática aguda. La amatoxina, uno de sus componentes es letal a dosis de 0.1 mg/kg y el manejo posterior a su ingesta no cuenta con pautas claramente establecidas, el mismo va a depender del tiempo que haya transcurrido desde la ingesta del hongo y puede llegar a ser tan invasivo como un trasplante hepático.

Despite it is a rare disease, the fungus poisoning can be lethal, mainly if it is with Amanita phalloides. This fungus have toxins that produce gastrointestinal alterations and acute liver failure. The amatoxin is one of its main components, its letal dosis is 0,1mg/kg and it doesn't have a established treatment, the outcome depends of the elapsed time between the ingest of the fungus and the medical treatment, which can be even a liver transplant.

Stabilization of Chronic Lymphatic Leukemia with Amanita phalloides: Effect of Additional Chelidonium majus. Case Report.

Objectives: Amanita phalloides contains amanitin, inhibiting RNA polymerase II. Partial inhibition with amanitin influences tumor cell - but not normal cell - activity. A patient with diagnosed B-cell chronic lymphatic leukemia was treated successfully for eight years with Amanita phalloides. However, the necessary dose for stabilization of the disease increased during this time. In addition thrombocyte levels decreased, indicating bone marrow affection. Therefore additional regimen was necessary. Methods: Chelidonium majus contains alkaloids with cytostatic and cytotoxic potential. In addition to Amanita, Chelidonium was applied. Results: During treatment with Amanita and Chelidonium, leukocyte levels and lactate-dehydrogenase levels were roughly unaffected, meaning there is no strong effect on tumor growth of cells, and no observable cell destruction. Anyhow, thrombocyte levels increased after the Chelidonium treatment, indicating an effect in the bone marrow. Conclusion: Chelidonium majus can be useful during Amanita therapy as a pulse to regenerate bone marrow affection.

Borrelia Infection Appears as Chronic Lymphocytic Leukemia: Therapy with Amanita phalloides and Terebinthina laricina.

Background: To date, Chronic Lymphocytic Leukemia (CLL) has been viewed as a malignant disease with tumor growth of cells. This hypothesis should be reviewed. Methods: A patient diagnosed with CLL is treated with Amanita phalloides, containing amanitin, inhibiting specifically tumor cell activity without affecting normal cells. Despite initial leukocyte cell count decrease, further therapy fails after eight months. He suffers from severe symptoms of inflammation, not specific for CLL. Additional Borrelia infection is diagnosed and Terebinthina laricina is applied. Results: Herxheimer reaction occurs some weeks later, accompanied by continuous leukocyte cell count drop to normal range within four months, even after stopping Amanita therapy. All symptoms of borreliosis and CLL vanished. Conclusion: CLL might be induced by a Borrelia-infection. This should be considered in diagnostic and therapeutic regimen.

Intoxicación con Amanita phalloides: serie de tres casos / Amanita phalloides poisoning: series of three cases

Se presenta una serie de tres casos de pacientes adultos con intoxicación por Amanita phalloides, ocurridos entre los años 2010 y 2011. Dos pacientes eran de sexo masculino, de 40 y 75 años de edad, y la mujer de 65 años. En todos los casos se asoció el cuadro clínico a la práctica de recolección casera de hongos para preparación de alimentos (actividad sostenida durante más de 10 años en todos los casos). La recolección se realizó en zonas de robles en un caso, y en zonas de castaños en los otros dos casos. En los tres casos la consulta se realizó entre las 16 y 36 h de la ingesta. Los tres pacientes desarrollaron diarrea, hepatopatía y falla hepática sin encefalopatía. A todos se les realizó tratamiento con carbón activado seriado, aspirado duodenal y penicilina endovenosa. El trasplante hepático fue necesario en uno de los casos. No hubo secuelas hepáticas en ninguno de los pacientes. Conclusiones: la práctica de recolección de hongos silvestres para consumo humano es un hábito riesgoso si se realiza por personas inexpertas en el reconocimiento de las especies tóxicas. Si bien la intoxicación por A. phalloides es un cuadro poco frecuente, su alta morbimortalidad hace indispensable el reconocimiento temprano y abordaje oportuno por parte de los médicos.

We present a series of three cases of Amanita phalloides poisoning in adult patients admitted during the period 2010 - 2011. Two patients were males of 40 and 75 years old, and the third was a woman of 65 years old. In all cases, the poisoning was associated with the home practice of collecting wild mushroom for cooking (activity traditionally carried out for more than 10 years in all cases). Mushroom collection was carried out in areas of oak trees for one case, and in areas of chestnuts trees in the two other cases. In all three cases the admission took place between 16 and 36 hours from intake. All three patients developed diarrhea, liver disease and liver failure without encephalopathy. All patients received treatment with activated charcoal (serial administration), duodenal aspiration and intravenous penicillin. Liver transplantation was necessary in one case. There were no hepatic sequelae in any patients. Conclusions: The practice of collecting wild mushrooms for human consumption is a risky habit if performed by people untrained in recognition of toxic species. While poisoning with A. phalloides is uncommon, its high mortality makes indispensable its early recognition and treatment by physicians.

Neutralización heteróloga e interacción de amanitinas con venenos de Bothropsy Crotalus y de abeja / Heterologous neutralization and interaction of toxic amanitins with Bothrops and Crotalus venoms, and honey bee venom / Neutralização heteróloga e interação das amanitinas tóxicas com veneno de Bothrops e Crotalus e veneno de abelha

En el presente trabajo se examinó la interacción de las amanitinas de Amanita phalloides (Basidiomycetes) con los venenos de las serpientes Bothrops neuwiedi diporus ("yarará pequeña"), B. alternatus ("yarará grande"), Crotalus durissus terrificus ("serpiente de cascabel") y de la abeja mielera Apis mellifera. Se aplicaron las técnicas de Ouchterlony, inmunotransferencia, electroforesis rocket y electroforesis en gel de poliacrilamida a los anti-venenos y anti-toxinas obtenidos por inmunización en caballos y/o en conejos. Los anti­sueros de serpientes y las amanitinas reaccionaron en forma cruzada, así como el veneno de abeja y las amanitinas. Cuando los venenos de Bothrops neuwiedii diporus y Crotalus durissus terrificus se preincubaron con las amanitinas y se analizaron por electroforesis en gel de poliacrilamida-dodecilsulfato de sodio (dodecylsulfate-polyacrylamide gel electrophoresis: SDS-PAGE), algunas bandas de proteínas desaparecieron y otras se redujeron notablemente. Estos resultados revelan por primera vez la interacción y la degradación de las proteínas de los venenos de serpientes por las amanitinas. Por otra parte, la modificación del tiempo de coagulación de la sangre humana, debida a los venenos, se corrigió con los ciclopéptidos de Amanita. Estos resultados también se informan por primera vez en este trabajo. La presencia de polipéptidos tóxicos en los venenos de serpientes y abejas, así como en A. phalloides y la reactividad cruzada demostradas en este trabajo, sugieren la existencia de epítopos comunes a todos ellos. Teniendo en cuenta estas reacciones, el uso de anti-venenos heterólogos parece ser de utilidad en el tratamiento del envenenamiento.

In the present work, the interaction of the amanitins of Amanita phalloides (Basidiomycetes) with the venoms of Bothrops neuwiedi diporus ("small yarará snake"), B. alternatus ("big yarará"), Crotalus durissus terrificus ("rattlesnake"), and honey bee Apis mellifera was examined. Ouchterlony, immunotransfer, rocket-electrophoresis, and polyacrylamide gel electrophoresis techniques were applied to anti-venoms and anti-toxins obtained by immunization in horses and/or in rabbits. Snake antisera and amanitins cross-reacted as well as bee venom and amanitins. When venoms of Bothrops neuwiedii diporus and Crotalus durissus terrificus were preincubated with amanitins and analysed by sodium dodecylsulfate-polyacrylamide gel electrophoresis (SDS-PAGE), some protein bands disappeared and others were significantly reduced. These results reveal for the first time the interaction and degradation of proteins in snake venoms by amanitins. Moreover, the modification of the human blood clotting time due to snake venoms was corrected by the Amanita cyclopeptides. These results are also reported for the first time in this work. The occurrence of toxic polypeptides in the snake and bee venoms as well as in A. phalloides, and the cross-reactivity demostrated herein, suggest the occurrence of epitopes common to all of them. Taking into account these reactions,the use of heterologous anti-venoms seems to be of value in envenomation treatment.

No presente trabalho foi examinada a interação das amanitinas de Amanita phalloides (Basidiomy­cetes) com os venenos das serpentes Bothrops neuwiedi diporus ("jararaca-cruzeira"), B. alternatus ("urutu"), Crotalus durissus terrificus ("serpente cascavel") e da abelha-europeia Apis mellifera. Foram aplicadas as técnicas de Ouchterlony, imunotransferência, eletroforese rocket e eletroforese em gel de poliacrilamida aos anti-venenos e anti-toxinas obtidos por imunização em cavalos e/ou em coelhos. Os anti-soros de serpentes e as amanitinas reagiram em forma cruzada, bem como o veneno de abelha e as amanitinas. Quando os venenos de Bothrops neuwiedii diporus e Crotalus durissus terrificus foram incubados previamente com as amanitinas e foram analisados por eletroforese em gel de poliacrilamida-dodecilsulfato de sódio (dodecylsulfate-polyacrylamide gel electrophoresis: SDS-PAGE), algumas faixas de proteínas desapareceram e outras se reduziram notavelmente. Estes resultados revelam por primeira vez a interação e a degradação das proteínas dos venenos de serpentes pelas amanitinas. Por outra parte, a modificação do tempo de coagulação do sangue humano, devido aos venenos, se corrigiu com os ciclopeptídeos de Amanita. Estes resultados também se informam por primeira vez neste trabalho. A presença de polipeptídeos tóxicos nos venenos de serpentes e abelhas, bem como em A. phalloides e a reatividade cruzada demonstradas neste trabalho, sugerem a existência de epítopos comuns a todos eles. Levando em consideração estas reações, o uso de anti-venenos heterólogos parece ser de utilidade no tratamento do envenenamento.