Traditional herbal medicine use doubled the risk of multi-organ dysfunction syndrome in children: A prospective cohort study.

BACKGROUND: Traditional herbal medicine (THM) is frequently used in pediatric populations in many low-income countries as a form of healthcare and has been associated with a range of adverse events, including liver toxicity, renal failure, and allergic reactions. Despite these concerns, its impact on multi-organ dysfunction syndrome (MODS) risk has not been thoroughly investigated. OBJECTIVE: This study aimed to investigate the incidence and predictors of MODS in a pediatric intensive care unit (PICU) in Ethiopia, with a focus on the association between THM use and the risk of MODS. METHODS: This was a single-center prospective cohort study conducted at a PICU in the university of Gondar Comprehensive Specialized hospital, Northwest Ethiopia. The study enrolled eligible patients aged one month to 18 years admitted to the PICU during the study period. Data on demographic characteristics, medical history, clinical and laboratory data, and outcome measures using standard case record forms, physical examination, and patient document reviews. The predictors of MODS were assessed using Cox proportional hazards models, with a focus on the association between traditional herbal medicine use and the risk of MODS. RESULTS: A total of 310 patients were included in the final analysis, with a median age of 48 months and a male-to-female ratio of 1.5:1. The proportion and incidence of MODS were 30.96% (95% CI:25.8, 36.6) and 7.71(95% CI: 6.10, 9.40) per 100-person-day observation respectively. Renal failure (17.74%), neurologic failure (15.16%), and heart failure (14.52%) were the leading organ failures identified. Nearly one-third of patients (32.9%) died in the PICU, of which 59.8% had MODS. The rate of mortality was higher in patients with MODS than in those without. The Cox proportional hazards model identified renal disease (AHR = 6.32 (95%CI: 3.17,12.61)), intake of traditional herbal medication (AHR = 2.45, 95% CI:1.29,4.65), modified Pediatric Index of Mortality 2 (mPIM 2) score (AHR = 1.54 (95% CI: 1.38,1.71), and critical illness diagnoses (AHR = 2.68 (95% CI: 1.77,4.07)) as predictors of MODS. CONCLUSION: The incidence of MODS was high. Renal disease, THM use, mPIM 2 scores, and critical illness diagnoses were independent predictors of MODS. A more than twofold increase in the risk of MODS was seen in patients who used TMH. Healthcare providers should be aware of risks associated with THM, and educate caregivers about the potential harms of these products. Future studies with larger sample sizes and more comprehensive outcome measures are needed.

Multiorgan failure caused by Chinese herbal medicine Xanthii Fructus poisoning: a case report.

BACKGROUND: Xanthii Fructus was used in the treatment of rhinitis and related nasal disease. It is the most commonly used chemically active component in compounds formulated for the treatment of rhinitis. However, poisoning, resulting in serious consequences, can easily occur owing to cocklebur overdose, improper processing, or usage without processing. CASE PRESENTATION: We reported on a 55-year-old man who experienced allergic rhinitis for 2.5 years. He ingested unprocessed Xanthii Fructus for 2 months as treatment. However, he developed anorexia; nausea; abdominal pain; general weakness; hiccups; oliguria and anuria; significantly elevated serum alanine aminotransferase, aspartate aminotransferase, and creatinine levels; and abnormalities in blood coagulation series. Nutritional support; daily drugs for liver protection, gastric protection, inflammation reduction; fresh plasma; and cryoprecipitate infusion were administered. Continuous venovenous hemodialysis (Prismaflex ST100) was also administered. However, the patient's multiple organ failure gradually worsened, ultimately leading to death. CONCLUSION: Xanthii Fructus poisoning affects multiple systems, and its clinical manifestations are complex. Therefore, it is easily misdiagnosed and missed. Along with careful inquiry of medical and medication history, early diagnosis and intervention are vital for a successful treatment. It is also important to educate people and create awareness about this poisoning. Therefore, this intractable case has great clinical significance.

Multi-organ dysfunction as a presentation of calcium channel blocker intoxication.

SummaryWe report the case of a 73-year-old woman who intentionally ingested 400 mg of amlodipine in a suicidal attempt who initially presented with hypotension which persisted despite aggressive therapy with fluid resuscitation, multiple pressor support, high-dose insulin therapy and calcium infusion. Her haemodynamic instability evolved to include bradycardia requiring atropine and transcutaneous pacing. Eventually she required salvage therapy with intravenous lipid emulsion (ILE) therapy . Despite all aggressive therapy, she developed multi-organ failure resulting in death. The literature on high-dose insulin euglycaemic therapy (HIET) and ILE therapy shows mixed results with some showing significant improvement in haemodynamic status. In our case, it had no significant positive impact on the outcome.

Intravenous rifampicin use in the management of amanita phalloides toxicity.

Context: Amanita phalloides related toxicity from amatoxins can result in acute liver and multi-organ failure and is responsible for 90% of all mushroom poisoning death. However, more evidence is needed in regards to different management strategies.Case details: We present two cases of amanita mushroom ingestion who were treated with intravenous rifampicin.Discussion: Further study is needed to establish the efficacy and role of rifampicin in amatoxin related mushroom poisoning.

An In Vivo Study on Intoxicating Effects of Nerium oleander Water Based Extract on Multiorgans of Wistar Rat.

This study was aimed to find histological changes in the extrahepatic organs, hepatic iron deposition, and gene expression of some iron regulatory proteins in rats after sterile muscle abscess during the acute intoxication of Nerium oleander leaves decoction. 10 ml/kg of the leaves extract was injected intramuscularly in Wistar rats (200-225 g, n = 4). Control animals received saline injection of matched volume. Animals were anesthetized and sacrificed after 3, 6, 12, and 24 h after administration of decoction. Lungs, kidney, spleen, and liver were extracted and processed for histopathological examination while portion of liver tissue was proceeded for iron regulatory gene expression quantification. Sections of all studied organs were found with signs of cellular dysfunction with infiltration of variety of leucocytes. In the lungs section at 3 h time point mononuclear cell infiltrates were observed while in alveolar tissue at 24 h time point dilation and even collapse in some of the alveoli were evident. In kidney sections distortion of renal tubules and epithelial cells with shrinkage of glomeruli was noted at all studied time points. In the splenic section of 12 h time point, degeneration, depopulation, and shrinkage of white pulp have been noted. Distension of the red pulp along with activation of splenic follicles was evident after 24 h onset of APR. Significant changes in the expression of acute phase cytokine and iron regulatory genes were noted. IL-6 and Hepc gene expression were strongly upregulated up to 12 h whereby Tf gene expression showed an early upregulation at 3 h time point followed by downregulation on later points while Hjv gene expression showed an overall downregulation at all study time points compared to control. It is concluded that inherent toxins present in the N. oleander can induce acute phase response and cause severe histological changes in the organs and marked changes in the regulation of iron regulatory proteins thus cannot be practiced routinely.

A Fatal Case of Amlodipine Toxicity Following Iatrogenic Hypercalcemia.

Using calcium salts in management of amlodipine overdose is challenging. A 25-year-old male with known history of adult polycystic kidney disease presented with hypotension, tachycardia, and intact neurological status after ingestion of 450 mg of amlodipine. Immediately, normal saline infusion and norepinephrine were initiated. Two grams of calcium gluconate was injected, followed by intravenous infusion of 1.16 mg/kg/h. The patient was put on insulin-glucose protocol to maintain euglycemia and hyperinsulinemia. Electrocardiography demonstrated junctional rhythm. Serum creatinine was 2.5 mg/dL with metabolic acidosis. By the end of 24 h post-admission, his consciousness, blood pressure, and urine output were normal. Almost 32 h post-admission, he became disoriented and his oxygen saturation decreased and therefore was mechanically ventilated. Second chest X-ray showed pulmonary edema. Serum calcium level increased to 26.1 mg/dL. Calcium was discontinued, and furosemide infusion and calcitonin were intravenously administrated. Urine output increased and hemodialysis improved pulmonary edema and serum calcium level with no change in consciousness. Three days after admission, the patient became anuric and developed multi-organ failure and died 5 days post-admission. To avoid the consequences of excessive infusion of calcium in renal failure patients, the minimum calcium dose with close monitoring is recommended.

13-Ethylberberine reduces HMGB1 release through AMPK activation in LPS-activated RAW264.7 cells and protects endotoxemic mice from organ damage.

High mobility group box 1 (HMGB1), a highly conserved non-histone DNA-binding protein, plays an important role in the pathogenesis of sepsis. Previously, the authors reported 13-ethylberberine (13-EBR) has anti-inflammatory and antibacterial effects. However, the effect of 13-EBR on HMGB1 release was not investigated. In the present study, it was hypothesized 13-EBR might reduce HMGB1 release by activating AMPK under septic conditions. The results obtained showed 13-EBR significantly reduced HMGB1 release from LPS-activated RAW264.7 cells, and that this reduction was reversed by silencing p38, or AMPK, or by co-treating cells with p38 MAPKinase inhibitor. 13-EBR increased the phosphorylations of p38 and AMPK, and the phosphorylation of p38 by 13-EBR was inhibited by AMPK-siRNA, indicating AMPK acted upstream of p38. In the lung tissues of LPS-treated mice, 13-EBR administration significantly increased p-AMPK but reduced inducible nitric oxide synthase (iNOS) protein levels. Hematoxylin and eosin staining revealed 13-EBR significantly reduced LPS-induced lung and liver damage. In addition, 13-EBR inhibited NF-kB in LPS-activated RAW264.7 cells, and in LPS-treated mice, 13-EBR administration significantly increased survival. Furthermore, co-administration of 13-EBR plus LPS prevented LPS-induced aortic rings hypocontractile response to phenylephrine in vitro. Taken together, these results indicate 13-EBR might offer a means of treating sepsis through AMPK activation.

A Case Report of Poisoning Caused by Incorrect Use of Salvia.

BACKGROUND Previous reports suggest that homoplantaginin, one of the compounds isolated from Salvia plebeia, has a protective and therapeutic effect on hepatocyte injury. We present a case of serious liver and kidney damage due to incorrect use of Salvia plebeia in a patient with a history of thyroid tumorectomy, who was successfully treated for poisoning with blood purification and systemic, comprehensive critical care. CASE REPORT A 54-year-old female patient with salvia intoxication combined with multiple organ dysfunction was transported to our emergency center by ambulance after presenting with nausea, vomiting, and skin yellowing. On arrival, she exhibited fatigue, dizziness, lightheadedness, yellowish discoloration of her skin, breathing difficulties, and low back pain, all of which was suggestive of salvia intoxication combined with multiple organ dysfunction. The treatment strategy was to immediately speed up the excretion of toxins and administered blood purification therapy. She also displayed disseminated intravascular coagulation (DIC), which was successfully treated with plasma infusion of blood coagulation factor combined with LMWH acupuncture therapy. CONCLUSIONS Salvia plebeia should only be considered for use in patients who have infectious disease or oxidative stress related disease and only at an appropriate dose. In addition, for patients with salvia poisoning, prompt administration of blood purification therapy and systemic comprehensive measures involving multiple supportive therapies can save such patients.

THE PROTECTIVE ROLE OF CURCUMIN IN ZYMOSAN-INDUCED MULTIPLE ORGAN DYSFUNCTION SYNDROME IN MICE.

AIM: Multiple Organ Dysfunction Syndrome (MODS) is characterized as progressive and uncontrolled inflammatory response which involves activation of inflammatory cascades, cytokines release, and endothelial dysfunction, leading to deterioration of several organ functions. Curcumin is a natural polyphenol related to the yellow color of turmeric and has been reported to exert an anti-inflammatory, anti-oxidative, and anti-tumor effect. We conducted the study to investigate the effects of curcumin in non-septic MODS caused by zymosan in mice model. METHOD: The mice were randomly allocated into five groups (six mice per group): control group (treated with physiological saline, 0.1 mL daily for 3 days before and 1 h after physiological saline treatment), DMSO group (treated with DMSO, 0.1 mL daily for 3 days before and 1 h after physiological saline treatment), Curcumin group (200 mg/kg, suspended in DMSO, in a final volume of 0.1 mL, used for 3 days daily before and 1 h after physiological saline treatment), Zymosan+DMSO group (treated with DMSO, 0.1 mL daily for 3 days before and 1 h after zymosan treatment) and Zymosan+ Curcumin group (treated with curcumin, suspended in DMSO at a dose of 0.1 mL daily for 3 days before and 1 h after zymosan treatment).Mice in groups were sacrificed, and then the blood and tissues were collected to evaluate the severity of acute peritonitis, tissue histopathological changes, NO formation, oxidative stress, PMN infiltration, cytokines production, organ function, and NF-κB activation 18 h after when zymosan or physiological saline was injected. In another set of experiments, the mice were also grouped (20 mice per group) for monitoring the loss of body weight and mortality for 7 days after zymosan or physiological saline administration. RESULTS: Curcumin induces a significant reduction of the volume exudate and the neutrophil infiltration. It also could exhibit an outstanding protective effect against histopathological injury by decreasing the NO formation, oxidative stress, cytokines production, and infiltration of inflammatory cells. The organ function is also improved by administration of curcumin. Moreover, the activation of NF-κB is attenuated by curcumin in the MODS mice model, suggesting that curcumin attenuated the zymosan-induced MODS via inhibiting the expression of NF-κB possibly. In addition, curcumin-treated mice were shown to alleviate the severity of MODS characterized by a minor systemic toxicity, less body weight loss, and lower mortality caused by zymosan administration. CONCLUSION: Curcumin attenuates zymosan-induced MODS.

Multiorgan dysfunction syndrome secondary to joint supplement overdosage in a dog.

A 5-year-old spayed female Bernese mountain dog, with a chief complaint of vomiting and melena ingested approximately 200 nutritional joint supplement tablets. Despite aggressive therapy, the patient developed a coagulopathy, pancreatitis, peritonitis, acute kidney injury, and was euthanized. Postmortem examination revealed myocardial necrosis, pneumonia, centrilobular hemorrhage and necrosis of the liver, vasculitis, and acute tubular necrosis.

Syndrome de défaillance multiviscérale secondaire à un surdosage d'un supplément pour articulation chez un chien. Une chienne Bouvier bernois stérilisée âgée de 5 ans présentée avec une plainte principale de vomissements et de mélæna avait ingéré environ 200 comprimés de suppléments nutritionnels pour les articulations. Malgré une thérapie agressive, la patiente a développé une coagulopathie, une pancréatite, une péritonite et une blessure aiguë aux reins et a été euthanasiée. L'autopsie a révélé une nécrose du myocarde, une pneumonie, une hémorragie centrilobulaire et une nécrose du foie, une vasculite et une nécrose tubulaire.(Traduit par Isabelle Vallières).

Continuous venovenous hemodiafiltration along with charcoal hemoperfusion for the management of life-threatening lercanidipine and amlodipine overdose.

Overdose with calcium channel blockers is uncommon, but is associated with high mortality. The management includes fluid resuscitation, calcium gluconate, glucagon, vasopressors, and high-dose insulin-euglycemia therapy. We describe a rare case of massive overdose of lercanidipine with shock, refractory to conventional therapies and multi-organ failure. Charcoal hemoperfusion with continuous venovenous hemodiafiltration was then used successfully and the patient showed remarkable recovery.

Fatal non-accidental alpha-lipoic acid intoxication in an adolescent girl.

The aim of our report is to increase awareness that the antioxidant alpha-lipoic acid, which is marketed primarily as weight loss and energy supplement, has potentially lethal effects. A 14-year-old girl ingested in suicidal intention a large amount of alpha-lipoic acid, which led to multiorgan failure and subsequent death within 24 h. Multiorgan failure consisted of decreased myocardial contractility, seizures, anuria, thrombocytopenia, and coagulopathy. Therapy consisted of ventilation, anticonvulsive treatment and circulatory support with high-dose catecholamines. According to alpha-lipoic acid serum levels following ingestion the girl must have ingested a minimum of 10 alpha-lipoic acid tablets of 600 mg each. This is the first report on a fatal case of alpha-lipoic acid ingestion, which is intended to inform physicians, pharmacists and patients about critical side effects of this allegedly innocuous drug.

Elements of margin of safety, toxicity and action of sodium selenite in a lipopolysaccharide rat model.

PROJECT: Both septic shock and sodium selenite (Na2SeO3) lead to multiple organ failure through oxidation. Na2SeO3 has direct oxidant effects above the nutritional level and indirect anti-oxidant properties. In a lipopolysaccharide (LPS) rat model we assessed margin of safety, toxicity and beneficial effect of pentahydrate Na2SeO3 (5H2O·Na2SeO3) at oxidant doses. PROCEDURE: In a three-step study on 204 rats we: (i) observed toxic effects of Na2SeO3 injected intraperitoneously (IP) and determined its Minimum Dose Without Toxic effect (MDWT) 0.25-0.35 mg/kg selenium (Se) content; (ii) injected IP LPS at 70% lethal dose (LD) followed, or not, one hour later by IP Na2SeO3 at MDWT and (iii) by doses>MDWT. At 48 h, in survivors, we measured plasma creatinine, lactate, aspartate and alanine aminotransferase (AST, ALT), nitric oxide (NO) and Se concentrations. RESULTS: (i) Na2SeO3 alone did not increase NO and lactate. Encephalopathy appeared at 1mg Se/kg. Creatinine increased at 1-1.75 mg Se/kg, AST, ALT at 3-4.5 mg Se/kg, and the minimum LD was 3 mg Se/kg. (ii) Mortality after LPS was 37/50 (74%, [62-86%]) vs. 20/30 (67%, [50-84%]) when followed by Na2SeO3 at MDWT (p=0.483) with a decreased in NO (-31%, p=0.038) a trend for lactate decrease (-19%, p=0.068) and an increased Se in plasma of survivals. (iii) All rats died at doses ≥0.6 mg/kg (p<0.001). CONCLUSION: Mechanisms of LPS and Na2SeO3 toxicity differ (i.e. NO, lactate). In septic shock 5H2O·Na2SeO3 toxicity increased, margin of safety decrease, but IP administration of dose considered as oxidant of 5H2O·Na2SeO3 showed beneficial effects.

Lethal cardiotoxicity, steatohepatitis, chronic pancreatitis, and acute enteritis induced by capecitabine and oxaliplatin in a 36-year-old woman.

A 36-year-old female was hospitalized with symptoms suggesting intestinal occlusion. She was diagnosed with adenocarcinoma of the ampulla of Vater (pT4N0 stage) and underwent cephalic duodenopancreatectomy 8 months ago. Five cycles of postoperative chemotherapy were administrated using capecitabine and oxaliplatin (CAPOX or XELOX), the last one being completed 1 month ago. During the present hospitalization, because of normal computed tomography and ultrasound abdominal examination, rehydration and antibiotherapy were administrated. However, 4 days after hospital admission, the patient died. At autopsy and histological examination, we found a severe myocardial sclerosis with large scarring areas, severe steatohepatitis, chronic pancreatitis with large fibrotic areas, and acute enteritis. Alcohol consumption was denied. The patient died due to associated heart, liver and pancreatic failure. This multiorgan toxicity and death following CAPOX regimen had not yet been reported in the literature. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/6472150549833105.

Fatal manganese intoxication due to an error in the elaboration of Epsom salts for a liver cleansing diet.

We describe the case of a 50-year-old man with a fatal intoxication after accidental massive oral ingestion of manganese. The patient presented with lethargy, diffuse abdominal pain, vomiting, and profuse diarrhea after ingesting Epsom salts (magnesium sulfate heptahydrate) during a liver cleansing diet. Despite intensive care management with intubation, prone position ventilation, continuous venovenous hemofiltration, and multiple transfusions, he progressed to refractory shock with multiple organ dysfunction resulting in death within 72 h. Similar patients arrived at several hospitals with identical epidemiology (all had ingested the same salt obtained in the same place). Clinical and forensic investigations (X-ray diffraction) discovered that the supplier had mistakenly prepared the salts with hydrated manganese sulfate instead of magnesium sulfate heptahydrate. The results enabled the other patients to be successfully treated for hydrated manganese sulfate intoxication with life support in the intensive care unit and chelation therapy (EDTA). We describe the clinical presentation of acute manganese poisoning and alert professionals to the risk of an increasingly popular diet. This case demonstrates the importance of collaboration between clinicians, pathologists, and forensic scientists to resolve a difficult-to-diagnose case.

Supplementation of Nigella sativa fixed and essential oil mediates potassium bromate induced oxidative stress and multiple organ toxicity.

The plants and their functional ingredients hold potential to cure various maladies and number of plants hold therapeutic potential. The present research was designed study the health promoting potential of black cumin (Nigella sativa) fixed oil (BCFO) and essential oil (BCEO) against oxidative stress with special reference to multiple organ toxicity. For the purpose, thirty rats (Strain: Sprague Dawley) were procured and divided into three groups (10 rats/group). The groups were fed on their respective diets i.e. D1 (control), D2 (BCFO @ 4.0%) and D3 (BCEO @ 0.30%) for a period of 56 days. Mild oxidative stress was induced with the help of potassium bromate injection @ 45 mg/Kg body weight. Furthermore, the levels of cardiac and liver enzymes were assayed. The results indicated that oxidative stress increased the activities of cardiac and liver enzymes. However, supplementation of BCFO and BCEO was effective in reducing the abnormal values of enzymes. Elevated levels of lactate dehydrogenase (LDH), CPK and CPK-MB were reduced from 456 to 231, 176 to 122 and 45 to 36mg/dL, respectively. Similarly, liver enzymes were also reduced. However, the results revealed that BCEO supplementation @ 0.30% is more effectual in ameliorating the multiple organ toxicity in oxidative stressed animal modelling. In the nutshell, it can be assumed that black cumin essential oil is more effective in reducing the extent of potassium bromate induced multiple organ toxicity (cardiac and liver enzymes imbalance) that will ultimately helpful in reducing the extent of myocardial and liver necrosis.