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Human-derived three-dimensional (3D) in vitro models are advanced human cell-based model for their complexity, relevance and application in toxicity testing. Intracellular accumulation of methylglyoxal (MGO), the most potent glycating agent in humans, mainly generated as a by-product of glycolysis, is associated with age-related diseases including neurodegenerative disorders.In our study, 3D human stem-cell-derived neuronal spheroids were set up and applied to evaluate cytotoxic effects after short-term (5 to 48 h) treatments with different MGO concentrations, including low levels, taking into consideration several biochemical endpoints.In MGO-treated neurospheroids, reduced cell growth proliferation and decreased cell viability occurred early from 5-10 μM, and their compactness diminished starting from 100 μM, apparently without affecting spheroid size. MGO markedly caused loss of the neuronal markers MAP-2 and NSE from 10-50 μM, decreased the detoxifying Glo1 enzyme from 50 μM, and activated NF-kB by nuclear translocation.The cytochemical evaluation of the 3D sections showed the presence of necrotic cells with loss of nuclei. Apoptotic cells were observed from 50 μM MGO after 48 h, and from 100 μM after 24 h. MGO (50–10 µM) also induced modifications of the cell–cell and cell-ECM interactions. These effects worsened at the higher concentrations (300–500 µM).In 3D neuronal spheroids, MGO tested concentrations comparable to human samples levels measured in MGO-associated diseases, altered neuronal key signalling endpoints relevant for the pathogenesis of neurodegenerative diseases and aging. The findings also demonstrated that the use of 3D neuronal spheroids of human origin can be useful in a strategy in vitro for testing MGO and other dicarbonyls evaluation.

Abstract Background In response to the COVID-19 health emergency, mass media widely spread guidelines to stop the virus transmission, leading to an excessive and unaware use of detergents and disinfectants. In Italy and in other countries this tendency caused a significant increase of exposures to these products in 2020. Evaluating data collected by the Italian Pavia Poison Centre (PPC), this study intends to examine the relationship between the COVID-19 lockdown and the variations of exposures to specific product categories possibly associated to the containment measures implemented. Simultaneously, this work shows the effectiveness of the European Product Categorisation System (EuPCS) in surveillance activities of dangerous chemicals. Methods Exposure cases managed by the PPC during March–May 2020 (lockdown) and during the same months of 2017–2018-2019 were compared. Differences in categorical variables were tested with the Chi-square test. The level of significance was set at Alpha = .05. The study included all EuPCS groups but specifically focused on cleaners, detergents, biocides and cosmetics. Results During the lockdown, calls from private citizens showed a highly significant increase (+ 11.5%, p

The phenomenon of acute behavioral disturbance is an underrecognized and potentially life-threatening syndrome, and sometimes an emergency in psychiatric settings. Patients presenting to the Italian emergency department (ED) with acute behavioral disturbances account for approximately 3.2% of all ED visits. The spectrum of behaviors and signs overlap with many clinical disease processes. In addition to patients with behavioral problems related to mental disorders or substance abuse, there is also a large group whose behavioral emergencies directly result from medical illness. The complexity of these patients, as well as the interdisciplinary nature of their care, requires a clear and consensual framework for care. A network of Italian scientific societies developed ten reccomendations for good clinical practice. The main purpose is to draw up a document that presents a standardized method for the organization of the care of patients with acute behavioral disorders in ED

Most cases of envenomation by common European vipers (Vipera berus) have not been reported to have neurotoxic manifestations. However, these manifestations have been demonstrated in some cases of envenomation by subspecies of V. berus, found in the Carpathian Basin region of south-eastern Europe. Here, we report the case of a 5-year-old girl from the south of Romania who presented symptoms of neurotoxicity, as well as other systemic and local symptoms, after being bitten by an adder of the V. berus subspecies. Treatment consisted of monovalent antivenom, a corticosteroid, and prophylactic enoxaparin. Neurotoxic manifestations of envenomation as well as other local and systemic symptoms improved within 5 days of treatment. The presented case shows that venom from V. berus subspecies found in the Carpathian Basin can have neurotoxic effects. This case also confirmed the efficacy of monospecific antivenom treatment in bringing about rapid and complete remission, following envenomation.

Infant botulism is a rare and underdiagnosed disease caused by BoNT-producing clostridia that can temporarily colonize the intestinal lumen of infants less than one year of age. The diagnosis may be challenging because of its rareness, especially in patients showing atypical presentations or concomitant coinfections. In this paper, we report the first infant botulism case associated with Cytomegalovirus coinfection and transient hypogammaglobulinemia and discuss the meaning of these associations in terms of risk factors. Intending to help physicians perform the diagnosis, we also propose a practical clinical and diagnostic criteria checklist based on the revision of the literature.

Botulinum neurotoxins (BoNTs) produced by Clostridia species are the most potent identified natural toxins. Classically, the toxic neurological syndrome is characterized by an (afebrile) acute symmetric descending flaccid paralysis. The most know typical clinical syndrome of botulism refers to the foodborne form. All different forms are characterized by the same symptoms, caused by toxin-induced neuromuscular paralysis. The diagnosis of botulism is essentially clinical, as well as the decision to apply the specific antidotal treatment. The role of the laboratory is mandatory to confirm the clinical suspicion in relation to regulatory agencies, to identify the BoNTs involved and the source of intoxication. The laboratory diagnosis of foodborne botulism is based on the detection of BoNTs in clinical specimens/food samples and the isolation of BoNT from stools. Foodborne botulism intoxication is often underdiagnosed; the initial symptoms can be confused with more common clinical conditions (i.e., stroke, myasthenia gravis, Guillain–Barré syndrome—Miller–Fisher variant, Eaton–Lambert syndrome, tick paralysis and shellfish or tetrodotoxin poisoning). The treatment includes procedures for decontamination, antidote administration and, when required, support of respiratory function; few differences are related to the different way of exposure.

Systemic toxicity associated with cobalt (Co) and chromium (Cr) containing metal hip alloy may result in neuropathy, cardiomyopathy, and hypothyroidism. However clinical management concerning chelating therapy is still debated in literature. Here are described two metal-on-metal hip-implanted patients in which N-acetyl-cysteine decreased elevated blood metal levels. A 67-year-old male who underwent Co/Cr hip implant in September 2009 referred to our Poison Control Centre for persisting elevated Co/Cr blood levels (from March 2012 to November 2014). After receiving oral high-dose N-acetyl-cysteine, Co/Cr blood concentrations dropped by 86% and 87% of the prechelation levels, respectively, and persisted at these latter concentrations during the following 6 months of follow-up. An 81-year-old female who underwent Co/Cr hip implant in January 2007 referred to our Centre for detection of high Co and Cr blood levels in June 2012. No hip revision was indicated. After a therapy with oral high-dose N-acetyl-cysteine Co/Cr blood concentrations decreased of 45% and 24% of the prechelation levels. Chelating agents reported in hip-implanted patients (EDTA, DMPS, and BAL) are described in few cases. N-acetyl-cysteine may provide chelating sites for metals and in our cases reduced Co and Cr blood levels and resulted well tolerable.

Ciguatera fish poisoning (CFP) is the most prevalent non-bacterial food-borne form of poisoning in French Polynesia, which results from the consumption of coral reef fish naturally contaminated with ciguatoxins produced by dinoflagellates in the genus Gambierdiscus. Since the early 2000s, this French territory has also witnessed the emergence of atypical forms of ciguatera, known as ciguatera shellfish poisoning (CSP), associated with the consumption of marine invertebrates. In June 2014, nine tourists simultaneously developed a major and persistent poisoning syndrome following the consumption of the gastropod Tectus niloticus collected in Anaho, a secluded bay of Nuku Hiva Island (Marquesas Archipelago, French Polynesia). The unusual nature and severity of this event prompted a multidisciplinary investigation in order to characterize the etiology and document the short/long-term health consequences of this mass-poisoning event. This paper presents the results of clinical investigations based on hospital medical records, medical follow-up conducted six and 20 months post-poisoning, including a case description. This study is the first to describe the medical signature of T. niloticus poisoning in French Polynesia and contributed to alerting local authorities about the potential health hazards associated with the consumption of this gastropod, which is highly prized by local communities in Pacific island countries and territories.

Infant Botulism is a form of human botulism in which ingested spores of Clostridium botulinum germinate, colonize the infant’s colon, in which they produce botulinum neurotoxin. After the toxin is absorbed, binding to peripheral cholinergic synapses occurs, causing flaccid paralysis. The incidence of infant botulism is low, but some underestimation is likely to exist: the disease is difficult to diagnose because its wide spectrum of clinical manifestations which are not pathognomic. Moreover, failure to recognise the disease is probably related to the low index of suspicion: in fact, the experience of clinicians is fundamental in recognising infant botulism. A specific project has been promote to improve knowledge of the disease by training physicians (pediatricians, neurologists, clinical toxicologists) to look out for the possible presence of Infant Botulism cases and improving public awareness through a prevention program. Standardization of therapeutic protocol also by treatment with specific therapeutic measures will be disseminated. A staff of physicians specialized in Clinical Toxicology will be available, 24 hours a day and seven days/week in the Pavia Poison Centre – National Toxicology Information Center. According to the project, this Centre acts as Reference Center for the clinical diagnosis and the treatment of infant botulism for the correct recognition of typical syndrome, the early diagnosis and the possible therapy with particular attention to antidotic treatment. The National Reference Centre for Botulism at the Istituto Superiore di Sanità will offer a 24-hours diagnostic laboratory service to support diagnose in suspected cases of botulism.

In the last ten years, increasing attention has been paid to the unavailability of antidotes in hospital pharmacies and emergency setting. Essential antidotes are not adequately stocked in many European and extra-European countries. The Pavia Poison Center (PPC) was charged by the National Institute of Health to conduct a survey in order to define the antidotes availability in emergency setting and to identify areas of possible improvement. Insufficient antidote stocking was defined as lack of the antidote or an amount inadequate to treat 1 seriously poisoned 70-kg patient for 24 hours. A national database (BaNdA) accessible through our PC website (www.cavpavia.it) that includes information on antidotes stocks of all hospital departments was created. The database information is available for all registered users and regularly updated: a simple query allows to identify hospitals provided with the antidote looked for at local, regional or national level. This database permit to optimize the antidotes procurement by EDs, through agreements with other hospitals serving the same area, to allow a more appropriate utilization of resources and to ameliorate the clinical management of the poisoned patient.

Carbon monoxide is still the most common unintentional poisoning in the Western Countries, and it may often produce potentially serious or lethal acute and delayed clinical manifestations. The considerable variety of symptoms of presentation is the main reason of the non infrequent diagnostic errors at admission. In emergency medicine it is essential to consider this diagnosis every time a patient is found in state of unconsciousness in an environment with possible exposure to CO, as well as in patients presenting with non-specific syndromes. The prompt identification of the intoxication is essential in order to plan a correct therapy at the proper time, and for preventing of risks of a late neurologic syndrome. After confirmation of the diagnosis through determination of COHb, that may nowadays be performed in a fast and non-invasive way both outside and inside hospitals thanks to a new generation of specific pulsoxyimeters, the patient has to be classified with a grading score for the severity depending on clinical presentation, that may be useful also for choice between normobaric or hyperbaric oxygen treatments. Eventually, it is essential to plan the follow-up for the patient during the months following the acute event.

Carbon monoxide is still the most common unintentional poisoning in the Western Countries, and it may often produce potentially serious or lethal acute and delayed clinical manifestations. The considerable variety of symptoms of presentation is the principal reason of the non infrequent diagnostic errors at admission. In emergency medicine it is essential to consider this diagnosis every time a patient is found in state of unconsciousness in an environment with possible exposure to CO, as well as in patients presenting with non-specific syndromes. The prompt identification of the intoxication is essential in order to plan a correct therapy at the proper time, and for prevention of risks of a late neurologic syndrome. Nowadays the diagnosis may be performed through determination of COHb in a fast and non-invasive way, both outside and inside hospitals, thanks to a new generation of specific pulsoxymetrers. After confirmation the patient has to be classified with a grading score for severity depending on clinical presentation, that may be useful also for the choice between normobaric or hyperbaric oxygen treatments. Eventually, it is essential to plan the follow up for the patient during the months following the acute event.

A 20-year-old healthy and apparently eupnoic man was admitted into our hospital because of a strong headache; we noticed tachycardia, tachypnea and decreased O2 saturation. A methemoglobin level of 29,5% was determined in the arterial blood. Some time before, a very old tank of ink had accidentally spilled over his working suit. The toxic agent was identified as aniline, a systemic asphyxiant that is well absorbed through the skin, causing systemic toxicity. The effects of skin absorption can be delayed for several hours. Most adverse health effects of aniline are due to the formation of methemoglobinemia, a disorder characterized by a form of hemoglobin that does not bind oxygen and impairs oxygen transport capacity. When its concentration is elevated in red blood cells a functional anemia and tissue hypoxia may occur. Organs with high oxygen demands (i.e. CNS, cardiovascular system, etc.) are usually the first to show toxic effects. The severity of methemoglobinemia symptoms is related to the amount of methemoglobin present in blood and range from a bluish discoloration of the skin and mucous membrane to weakness, seizures, difficulty in breathing, dysrhythmias, acidosis, cardiac or neurologic ischemia. Treatment is determined by symptoms. The first step of therapy is to remove patient from the source of exposure and ensure adequate skin and eye decontamination. It is necessary to ensure adequate ventilation with 100% O2, too. Methylene blue is the first-line antidotal agent.

The use of naloxone in emergency medicine is primarily connected to the treatment of a syndrome known as overdose, which is cause by non-essential use of heroin and certain opioid agonists. The dose of naloxone required to be efficacious depends on the quantity of opioid assumed, its receptorial affinity and its kinetics: in propoxyphene and pentazocine intoxication, for instance, higher doses are require than those needed in the treatment of morphine or heroin overdose. Intravenous administration is the most efficacious and fast-acting method: however, in certain cases, and depending on aspects that are typical of overdose patient management (e.g. the difficulties connected to vein access, skin scarring, severe hypotension), alternative pathways may be used. These include intraand sub-lingual and intratracheale administration, inhalatory administration via nebulisation (possible in the presence of respiratory action only), and intramuscular and subcutaneaous administration (which are efficacious in the absence of hypoperfusion). However, the most promising means of administration would appear to be intranasal administration, thanks to the relative ease of access, lower risk of contact with bodily fluids and the excellent bioavailability and rapidity of the effect, which is similar to that achieved with intravenous administration.

An 8-month old girl, weighing 9 kg, was brought by her parents at 8.15 am to the Emergency Department (ED) for a progressive worsening of weakness and acute respiratory failure. On admission, the baby presented with poor oral intake, a weak cry and extremely weak muscular body control. Poor gag and suck, unreactive mydriasis, hypotonia, lethargy and absence of peristalsis were noted. Laboratory data showed severe respiratory acidosis. Chest X-ray, electroencephalography, encephalic CT scan and MRI were all normal, as were cerebrospinal fluid analysis and viral tests. Orotracheal intubation and continuous mechanical ventilation were applied. The patient received fluids, corticosteroids, aerosol therapy, large-spectrum antibiotics and enteral- nutrition. Further investigation revealed ingestion of an improperly prepared homecanned homogenized turkey meal. Type A botulinum neurotoxin was identified. Trivalent botulinum antitoxin, prostigmine and oral activated charcoal were administered. Generalized flaccid paralysis, areflexic bilateral mydriasis, gastric stasis and deep coma persisted for the duration of the hospital stay, and the patient died of severe respiratory failure and cardiac arrest 12 days after ED admission. Botulism poisoning should be suspected in any infant presenting with feeding difficulties, constipation, descendent paralysis or acute respiratory failure. Supportive treatment and antidotal therapy should be performed as soon as a clinical diagnosis is made. We describe a case of foodborne botulism in an 8-month old infant caused by ingestion of an improperly prepared home-canned homogenized turkey meal, representing the youngest fatal case reported in medical literature.