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Journal of Medical Toxicology :... Oct 2023Since 2010, medical toxicology physicians from the American College of Medical Toxicology (ACMT) Toxicology Investigators Consortium (ToxIC) have provided reports on...
Since 2010, medical toxicology physicians from the American College of Medical Toxicology (ACMT) Toxicology Investigators Consortium (ToxIC) have provided reports on their in-hospital and clinic patient consultations to a national case registry, known as the ToxIC Core Registry. De-identified patient data entered into the registry includes patient demographics, reason for medical toxicology evaluation, exposure agents, clinical signs and symptoms, treatments and antidotes administered, and mortality. This thirteenth annual report provides data from 7206 patients entered into the Core Registry in 2022 by 35 participating sites comprising 52 distinct healthcare facilities, bringing the total case count to 94,939. Opioid analgesics were the most commonly reported exposure agent class (15.9%), followed by ethanol (14.9%), non-opioid analgesic (12.8%), and antidepressants (8.0%). Opioids were the leading agent of exposure for the first time in 2022 since the Core Registry started. There were 118 fatalities (case fatality rate of 1.6%). Additional descriptive analyses in this annual report were conducted to describe the location of the patient during hospitalization, telemedicine consultations, and addiction medicine treatments.
Topics: Humans; United States; Drug Overdose; Antidotes; Registries; Analgesics, Non-Narcotic; Ethanol; Analgesics, Opioid; Poisoning; Toxicology
PubMed: 37644342
DOI: 10.1007/s13181-023-00962-2 -
The Journal of Pharmacology and... Jan 2024Inhaled toxicants are used for diverse purposes, ranging from industrial applications such as agriculture, sanitation, and fumigation to crowd control and chemical... (Review)
Review
Inhaled toxicants are used for diverse purposes, ranging from industrial applications such as agriculture, sanitation, and fumigation to crowd control and chemical warfare, and acute exposure can induce lasting respiratory complications. The intentional release of chemical warfare agents (CWAs) during World War I caused life-long damage for survivors, and CWA use is outlawed by international treaties. However, in the past two decades, chemical warfare use has surged in the Middle East and Eastern Europe, with a shift toward lung toxicants. The potential use of industrial and agricultural chemicals in rogue activities is a major concern as they are often stored and transported near populated areas, where intentional or accidental release can cause severe injuries and fatalities. Despite laws and regulatory agencies that regulate use, storage, transport, emissions, and disposal, inhalational exposures continue to cause lasting lung injury. Industrial irritants (e.g., ammonia) aggravate the upper respiratory tract, causing pneumonitis, bronchoconstriction, and dyspnea. Irritant gases (e.g., acrolein, chloropicrin) affect epithelial barrier integrity and cause tissue damage through reactive intermediates or by direct adduction of cysteine-rich proteins. Symptoms of CWAs (e.g., chlorine gas, phosgene, sulfur mustard) progress from airway obstruction and pulmonary edema to acute lung injury (ALI) and acute respiratory distress syndrome (ARDS), which results in respiratory depression days later. Emergency treatment is limited to supportive care using bronchodilators to control airway constriction and rescue with mechanical ventilation to improve gas exchange. Complications from acute exposure can promote obstructive lung disease and/or pulmonary fibrosis, which require long-term clinical care. SIGNIFICANCE STATEMENT: Inhaled chemical threats are of growing concern in both civilian and military settings, and there is an increased need to reduce acute lung injury and delayed clinical complications from exposures. This minireview highlights our current understanding of acute toxicity and pathophysiology of a select number of chemicals of concern. It discusses potential early-stage therapeutic development as well as challenges in developing countermeasures applicable for administration in mass casualty situations.
Topics: Humans; Lung; Chlorine; Chemical Warfare Agents; Phosgene; Acute Lung Injury; Irritants
PubMed: 37863486
DOI: 10.1124/jpet.123.001822 -
The Veterinary Clinics of North... Apr 2024Boxelder and sycamore maple contain hypoglycin A (HGA), the toxic metabolite of which, MCPA-CoA, inhibits fatty acid β-oxidation, causing seasonal pasture myopathy... (Review)
Review
Boxelder and sycamore maple contain hypoglycin A (HGA), the toxic metabolite of which, MCPA-CoA, inhibits fatty acid β-oxidation, causing seasonal pasture myopathy (SPM) or atypical myopathy (AM), respectively. White snakeroot and rayless goldenrod contain multiple benzofuran ketones (BFKs). The identity/toxicity of BFKs appear variable, possibly involving interactions between toxins/toxic metabolites, but ultimately inhibit cellular energy metabolism. Unthrifty horses grazing sparse pastures during the fall appear predisposed to these plant-associated, frequently fatal, toxic myopathies. Toxidromes are characterized by varying degrees of rhabdomyolysis and cardiac myonecrosis, with plant toxins remaining toxic in hay and being excreted in milk.
Topics: Animals; Horses; Myotoxicity; Plant Poisoning; Horse Diseases; Plants, Toxic; Muscular Diseases
PubMed: 38151404
DOI: 10.1016/j.cveq.2023.11.001 -
Anasthesiologie, Intensivmedizin,... Jul 2023Poisoning of children requires quick and rational action. It is crucial to recognize a poisoning, to interpret the symptoms correctly, and to assess the severity of the...
Poisoning of children requires quick and rational action. It is crucial to recognize a poisoning, to interpret the symptoms correctly, and to assess the severity of the poisoning as precisely as possible. This is the best way to find the optimal therapy for each patient.Cases of suspected poisoning are common in childhood. The risk of a potential poisoning must be recognized and interpreted correctly. Based on this, symptomatic and specific therapy can be carried out. The poisons information centres have a great experience in the diagnosis and treatment of poisonings and can help the attending physicians to plan the further therapeutic steps.Both the hazard of a toxic substance and a realistic exposure assessment must be considered. This is especially crucial in cases of suspected poisoning of (still) mostly asymptomatic patients. This is the way to prevent overtreatment without overlooking dangerous poisonings.
Topics: Adolescent; Child; Humans; Poisoning
PubMed: 37582355
DOI: 10.1055/a-2120-6006 -
JAAPA : Official Journal of the... Oct 2023Diagnosis of carbon monoxide (CO) poisoning is challenging, as it is generally based on a history of present illness leading to clinical suspicion. CO is a tasteless,...
Diagnosis of carbon monoxide (CO) poisoning is challenging, as it is generally based on a history of present illness leading to clinical suspicion. CO is a tasteless, odorless, and colorless gas that has become known as the "silent killer." CO poisoning affects approximately 50,000 people in the United States each year and presents with wide range of nonspecific symptoms. Patients often do not know that they are being exposed to CO gas; it is therefore important to ask pertinent questions when taking a patient's history. Treatment consists of oxygen therapy. If a diagnosis is not made and treatment is not administered promptly, complications may occur.
Topics: Humans; Carbon Monoxide Poisoning; Affect; Oxygen Inhalation Therapy
PubMed: 37751267
DOI: 10.1097/01.JAA.0000977740.22781.6b -
The EMBO Journal Jul 2023Enhanced expression of the cold-shock protein RNA binding motif 3 (RBM3) is highly neuroprotective both in vitro and in vivo. Whilst upstream signalling pathways leading...
Enhanced expression of the cold-shock protein RNA binding motif 3 (RBM3) is highly neuroprotective both in vitro and in vivo. Whilst upstream signalling pathways leading to RBM3 expression have been described, the precise molecular mechanism of RBM3 cold induction remains elusive. To identify temperature-dependent modulators of RBM3, we performed a genome-wide CRISPR-Cas9 knockout screen using RBM3-reporter human iPSC-derived neurons. We found that RBM3 mRNA and protein levels are robustly regulated by several splicing factors, with heterogeneous nuclear ribonucleoprotein H1 (HNRNPH1) being the strongest positive regulator. Splicing analysis revealed that moderate hypothermia significantly represses the inclusion of a poison exon, which, when retained, targets the mRNA for nonsense-mediated decay. Importantly, we show that HNRNPH1 mediates this cold-dependent exon skipping via its thermosensitive interaction with a G-rich motif within the poison exon. Our study provides novel mechanistic insights into the regulation of RBM3 and provides further targets for neuroprotective therapeutic strategies.
Topics: Humans; Poisons; Cold Shock Proteins and Peptides; Cold Temperature; RNA, Messenger; RNA-Binding Proteins
PubMed: 37248947
DOI: 10.15252/embj.2022113168 -
Clinical Toxicology (Philadelphia, Pa.) Dec 2023Fifty years ago, basic scientific studies and the availability of assay methods made the assessment of risk in paracetamol (acetaminophen) poisoning possible. The use of... (Review)
Review
Fifty years of paracetamol (acetaminophen) poisoning: the development of risk assessment and treatment 1973-2023 with particular focus on contributions published from Edinburgh and Denver.
INTRODUCTION
Fifty years ago, basic scientific studies and the availability of assay methods made the assessment of risk in paracetamol (acetaminophen) poisoning possible. The use of the antidote acetylcysteine linked to new methods of risk assessment transformed the treatment of this poisoning. This review will describe the way in which risk assessment and treatments have developed over the last 50 years and highlight the remaining areas of uncertainty.
METHODS
A search of PubMed and its subsidiary databases revealed 1,166 references published in the period 1963-2023 using the combined terms "paracetamol", "poisoning", and "acetylcysteine". Focused searches then identified 170 papers dealing with risk assessment of paracetamol poisoning, 141 with adverse reactions to acetylcysteine and 114 describing different acetylcysteine regimens. To manage the extensive literature, we focused mainly on contributions made by the authors during their time in Edinburgh and Denver.
DOSE AND CONCENTRATION RESPONSE
The key relationship between paracetamol dose and toxicity risk was established in 1971 and led to the development of the Rumack-Matthew nomogram from data collected in Edinburgh.
MECHANISMS OF TOXICITY
A series of papers on the mechanisms of toxicity were published in 1973, and these showed that paracetamol hepatotoxicity was caused by the formation of a toxic intermediate epoxide metabolite normally detoxified by glutathione but which, in excess, was bound covalently to hepatic enzymes and proteins. An understanding of the relationship between the rate of paracetamol metabolism, paracetamol concentration, and toxic hazard in humans soon followed.
ANTIDOTE DEVELOPMENT AND EFFICACY IN PATIENTS
These discoveries were followed by the testing of a range of sulfhydryl-donors in animals and "at risk" patients. Acetylcysteine was developed as the lead intravenous antidote in the United Kingdom. The license holder in the United States refused to make an intravenous formulation. Thus, oral acetylcysteine became the antidote trialed in the United States National Multicenter Study. Intravenous acetylcysteine regimens used initially in the United Kingdom and subsequently in the United States used loading doses of 150 mg/kg over 15 minutes or one hour, 50 mg/kg over four hours, and 100 mg/kg over 16 hours. These regimens were associated with adverse drug reactions (nausea, vomiting and anaphylactoid reactions) and hence, treatment interruption. Newer dosing regimens now give loading doses more slowly. One, the Scottish and Newcastle Anti-emetic Pretreatment protocol, using an acetylcysteine regimen of 100 mg/kg over two hours followed by 200 mg/kg over 10 hours, has been widely adopted in the United Kingdom. A cohort comparison study suggests this regimen has comparable efficacy to standard regimens and offers opportunities for selective higher acetylcysteine dosing.
RISK ASSESSMENT AT PRESENTATION
No dose-ranging studies with acetylcysteine were done, and no placebo-controlled studies were performed. Thus, there is uncertainty regarding the optimal dose of acetylcysteine, particularly in patients ingesting very large overdoses of paracetamol. The choice of intervention concentration on the Rumack-Matthew nomogram has important consequences for the proportion of patients treated. The United States National Multicenter Study used a "treatment" line starting at 150 mg/L (992 µmol/L) at 4 hours post overdose, extending to 24 hours with a half-life of 4 hours, now standard there, and subsequently adopted in Australia and New Zealand. In the United Kingdom, the treatment line was initially 200 mg/L (1,323 µmol/L) at 4 hours (the Rumack-Matthew "risk" line). In 2012, the United Kingdom Medicines and Healthcare products Regulatory Agency lowered the treatment line to 100 mg/L (662 µmol/L) at 4 hours for all patients, increasing the number of patients admitted and treated at a high cost. Risk assessment is a key issue for ongoing study, particularly following the development of potential new antidotes that may act in those at greatest risk. The development of biomarkers to assess risk is ongoing but has yet to reach clinical trials.
CONCLUSION
Even after 50 years, there are still areas of uncertainty. These include appropriate acetylcysteine doses in patients who ingest different paracetamol doses or multiple (staggered) ingestions, early identification of at-risk patients, and optimal treatment of late presenters.
Topics: Humans; Acetaminophen; Antidotes; Acetylcysteine; Antiemetics; Risk Assessment; Drug Overdose; Analgesics, Non-Narcotic; Chemical and Drug Induced Liver Injury; Multicenter Studies as Topic
PubMed: 38197864
DOI: 10.1080/15563650.2023.2293452 -
International Journal of Environmental... Aug 2023With poultry products as one of the leading reservoirs for the pathogen, in a typical year in the United States, it is estimated that over one million individuals... (Review)
Review
With poultry products as one of the leading reservoirs for the pathogen, in a typical year in the United States, it is estimated that over one million individuals contract non-typhoidal infections. Foodborne outbreaks associated with infections in poultry, thus, continue to remain a significant risk to public health. Moreover, the further emergence of antimicrobial resistance among various serovars of is an additional public health concern. Feeding-based strategies (such as use of prebiotics, probiotics, and/or phytobiotics as well as essential oils), non-feeding-based strategies (such as use of bacteriophages, vaccinations, and in ovo strategies), omics tools and surveillance for identifying antibiotic-resistance genes, post-harvest application of antimicrobials, and biosecurity measures at poultry facilities are practical interventions that could reduce the public health burden of salmonellosis and antibiotic resistance associated with poultry products. With the escalating consumption of poultry products around the globe, the fate, prevalence, and transmission of in agricultural settings and various poultry-processing facilities are major public health challenges demanding integrated control measures throughout the food chain. Implementation of practical preventive measures discussed in the current study could appreciably reduce the public health burden of foodborne salmonellosis associated with poultry products.
Topics: Humans; Animals; Poultry; Public Health; Salmonella Food Poisoning; Salmonella Infections; Poultry Products
PubMed: 37681794
DOI: 10.3390/ijerph20176654 -
Harmful Algae Aug 2023Public awareness about Benthic Harmful Algal Blooms (BHABs) and their negative impacts has increased substantially over the past few decades. Even so, reports of BHABs... (Review)
Review
Public awareness about Benthic Harmful Algal Blooms (BHABs) and their negative impacts has increased substantially over the past few decades. Even so, reports of BHABs remain relatively scarce in South America (SA). This paper provides a comprehensive overview of the current state of knowledge on BHABs in the continent, by integrating data from published articles, books, and technical reports. We recorded ∼300 different occurrences of potentially toxic BHAB species over the Caribbean, Atlantic and Pacific coasts, mostly in marine (>95%) but also in estuarine areas located from 12⁰36' N to 54⁰53' S. Over 70% of the data was published/released within the past 10 years, and ∼85% were concentrated in Brazil, Venezuela, Ecuador and Colombia. Benthic species were mainly associated with macroalgae, seagrass and sediment. Incidental detection in the plankton was also relevant, mainly in places where studies targeting BHAB species are still rare, like Argentina, Uruguay, Chile and Peru. The study listed 31 infrageneric taxa of potentially toxic benthic dinoflagellates and eight of estuarine cyanobacteria occurring in SA, with the greatest species diversity recorded in the equatorial-tropical zone, mainly in northeastern Brazil (Atlantic), Venezuela and Colombia (Caribbean), and the Galapagos Islands, Ecuador (Pacific). Local strains of Amphidinium, Gambierdiscus, Coolia and Prorocentrum spp. produced toxic compounds of emerging concern. Prorocentrum lima species complex was the most common and widely distributed taxon, followed by Ostreopsis cf. ovata. In fact, these two dinoflagellates were associated with most BHAB events in SA. Whereas the former has caused the contamination of multiple marine organisms and cases of Diarrhetic Shellfish Poisoning in subtropical and temperate areas, the latter has been associated with faunal mortalities and is suspected of causing respiratory illness to beach users in tropical places. Ciguatera Poisoning has been reported in Colombia (∼240 cases; no deaths) and Venezuela (60 cases; two deaths), and may be also a risk in other places where Gambierdiscus spp. and Fukuyoa paulensis have been reported, such as the Galapagos Islands and the tropical Brazilian coast. Despite the recent advances, negative impacts from BHABs in SA are intensified by limited research/training funding, as well as the lack of official HAB monitoring and poor analytical capability for species identification and toxin detection in parts of the continent.
Topics: Microalgae; Dinoflagellida; Harmful Algal Bloom; Ciguatera Poisoning; Brazil
PubMed: 37544678
DOI: 10.1016/j.hal.2023.102478 -
Cutis Mar 2024Scorpionfish are among the most venomous creatures found in American and Caribbean seas. Their envenomation is responsible for considerable morbidity and socioeconomic... (Review)
Review
Scorpionfish are among the most venomous creatures found in American and Caribbean seas. Their envenomation is responsible for considerable morbidity and socioeconomic burden associated with marine animal injuries. Avoiding physical contact with scorpionfish through proper identification prevails as the chief prevention method for stings. This article discusses common features of scorpionfish as well as the clinical presentation and treatment options following exposure to its toxins.
Topics: Humans; Animals; Bites and Stings; Fishes, Poisonous; Fish Venoms; Antivenins
PubMed: 38648593
DOI: 10.12788/cutis.0973