Clinical characteristics of acute lacosamide poisoning: Pavia Poison Control Centre experience.

AIMS: Lacosamide is a third-generation antiepileptic drug used as adjunctive therapy for partial seizures. Since its approval in 2008 very few cases of lacosamide overdose have been described in literature. The aim of our study was to evaluate clinical characteristics of acute lacosamide poisoning. METHODS: A retrospective observational study was performed including all cases of acute lacosamide poisoning referred to Pavia Poison Control Centre from January 2012 to December 2021. For each patient age, sex, ingested dose, coingestants, clinical manifestations, treatment and outcome were collected. RESULTS: A total of 31 subjects (median age 39 years, [interquartile range: 26.5-46.5]; females 22/31) were included. The median lacosamide ingested dose was 1500 mg [650-2800]. In 35.5% of cases lacosamide was the single ingested substance, while in 64.5% coingestants were also present. Coingestants varied from a minimum of 1 to a maximum of 3, with the more common being benzodiazepines and valproic acid. Clinical manifestations were present in 87% patients the most common were: vomiting (29%); seizures (29%), coma (25.8%), drowsiness (25.8%), confusion (12.9%), agitation (12.9%), tachycardia (12.9%), tremors (9.7%), bradycardia (9.7%), headache (6.5%) and hypertension (3.2%). The median lacosamide ingested dose was significantly higher in patients that experienced coma compared to patient who did not (2800 vs. 800 mg; P = .0082). Orotracheal intubation was necessary in 32.3% of patients. All patients fully recovered. CONCLUSION: Lacosamide acute overdose may lead to a severe clinical picture. Dentral nervous system symptoms predominated, particularly seizures and coma occurred in a high percentage of cases.

Coronary thrombosis after European adder bite in a patient on dual antiplatelet therapy: A case report.

INTRODUCTION: Until now very few cases of an adverse cardiovascular event have been described following European viper envenomation (Aravanis et al., 1982) (Aravanis et al., 1982) (Aravanis et al., 1982) (Aravanis et al., 1982). In fact, cardiac toxicity following snake bite is rare and primary reported from tropical and subtropical areas with only twenty-one cases of myocardial infarction reported in literature. Herein, we report a case of European viper envenomation associated with coronary artery thrombosis complicated by acute myocardial infarction and cardiac arrest. CASE REPORT: A 62-year-old man, with a history of cardiovascular disease, on dual antiplatelet therapy with ticagrelor and acetylsalicylic acid, was admitted to the Emergency Department, after a bite, on the right hand, from a snake recognized by a herpetologist as a Vipera aspis francisciredi. At ED presentation, 2 hours after the bite, he manifested with vomiting, hypotension (90/60 mmHg) and mild oedema at the bite site. Standard electrocardiogram and troponin were normal at admission. One hour after the admission the patient developed cardiocirculatory arrest (ACC) with return of spontaneous circulation (ROSC) after cardiopolmunary resuscitation. Post ROSC-ECG showed an ST-elevation on anteroseptal and lateral leads and 1-vial of Viper Venom Antitoxin (Biomed®) was i.v. administered. During the next 3 hours three other episodes of ACC occurred, always with restoration of spontaneous circulation. Percutaneous transluminal coronary angiography showed a thrombus on the bifurcation of anterior descending coronary artery and diagonal 1 without an underlined atherosclerotic plaque. Neurologic clinical manifestations also occurred 12 hours after the bite: bilateral ptosis and facial paresthesia and a second vial of the same viper antivenom administered. The patient was discharged after 9 days of hospitalization without sequelae. CONCLUSIONS: Our case show that cardiotoxicity is a rare but possible event after snake envenomation in Europe, even if with mechanisms remains to be studied. Vipera aspis has been known to cause primarily neurotoxic manifestations, but a coagulation factor X activator have also been isolated from its venom. Moreover, a specific serine peptidase that can target both PAR1 and PAR3, that are responsible for alternate pathways of platelet aggregation, have been characterized in the venom of a viper. Coronary thrombosis in our case could thus be secondary to a combination of prothrombotic systemic state and platelets dysfunction, in a patient with predisposing factors. Antivenom specific antidotal therapy role in preventing cardiotoxicity still need to be elucidated, but it remains the mainstay of treatment together with coronary angiography if necessary.

Case series of Chlorophyllum molybdites intoxication in Sicily: an "alien" mushroom species in Europe.

INTRODUCTION: Mushroom poisoning is an important cause of intoxication worldwide. The toxic mechanism remains frequently unknown and the diffusion of non-endemic species may cause the emergence of new syndromes. An example is the widespread of Chlorophyllum molybdites in Sicily. CASE SERIES: Pavia Poison Centre was recently involved in the management of 10 intoxications caused by the ingestion of Chlorophyllum molybdites, which was not considered part of the Italian mycological species. The clinical syndrome was characterized by severe gastrointestinal symptoms. In paediatric or vulnerable patients, it may bring to hypovolemic shock that necessitate intensive support. The possibly confusion with amatoxins-containing mushrooms may complicate the management. CONCLUSIONS: Chlorophyllum molybdites is widespread on the oriental coast of Sicily and it could be confused with "parasol mushrooms". Cooperation between emergency physicians, clinical toxicologist and mycologist, supported by improving of laboratory tests, is essential for the appropriate clinical management. Climate changes and migration flows can interfere with the diffusion of new species and the development of novel syndromes.

Accidental ingestion of sodium molybdate at the workplace followed by short-term biomonitoring.

INTRODUCTION: Most of the molybdenum (Mo) is used in metallurgical applications, the tetrathiomolybdate form is an experimental chelating agent for Wilson's disease. Human data of acute Mo exposure are lacking and, no report of no-observed-adverse-effect level (NOAEL) has been described until now. Case-study: We report a case of acute occupational exposure to molybdenum, with the related plasma and urine molybdenum concentrations, caused by an accidental ingestion of a sip of an anti-corrosion liquid for metal containing sodium molybdate. Our purpose was to evaluate potential systemic toxicity of molybdenum and to evaluate the dose-response/dose-effect relationship. We estimated the amount of ingested molybdenum to make a mg/kg relationship and performed repeated urine and plasma molybdenum determinations. The patient was hospitalized for three days to monitor possible development of acute symptoms/biochemical alterations. DISCUSSION: We estimated the amount of the sip around 50 ml, with an estimation of a total of 5 gr of sodium molybdate that, for the patient bodyweight of 80 kg, would mean 62,5 mg/kg of ingested Mo. Blood and urine samples collected 2 hours after ingestion showed 50 mcg/L (reference range: 0.43 - 1.8 mcg/L) and 630 mcg/L (refence range: up to 116 mcg/L) of Mo respectively, confirming acute exposure. The patients remained asymptomatic confirming that an estimated oral dose of Mo of 62.5 mg/kg was not associated with adverse effects. CONCLUSIONS: Our value, being extrapolated by a single case, will require further confirmations from other studies to allow a full evaluation of a NOAEL. Nevertheless, it does not preclude its use in evaluating the probable absence of adverse effect in the context of acute Mo exposure.

Guttate psoriasis: a case of unusual evolution of an occupation-related skin chemical burns.

INTRODUCTION: Chemical burns are a risk in domestic and occupational accidents due to the common use of caustic agents. Long-term sequelae are normally due to the amount of skin and underlying tissues damaged. We describe a case of work-related chemical burns with unusual evolution in guttate psoriasis. CASE REPORT: A 36 years-old man was admitted to the Emergency Department (ED) three-hours after a work accident. During the cleaning of an industrial hydraulic system, a jet of hydrochloric acid 20% injured his face and upper limbs. At ED admission, he presented first and second-degree skin burns on the frontal region, on the scalp, on the right forearm, and earlobe. Plastic surgery management consisted in wound topical dressing with silver sulfadiazine and paraffin gauze twice a week for one month. Forty-eight hours after the latter topical treatment (45-days after the work accident), in the same anatomical regions of the previous burn scars, he developed a skin reaction with itchy erythema. The application of topical products was suspended without improvement, excluding an allergic reaction. Within few days, a generalized guttate psoriasis was evident on the whole body. DISCUSSION: Despite many prevention actions, work-related burns are a relatively common cause of hospitalization and may involve up to 80% of patients admitted to a burn unit. Guttate psoriasis has not been described as a sequelae of chemical burns. In our case, the others most frequent factors causing guttate psoriasis have been ruled out. Considering the temporal link between the development of guttate psoriasis and the work accident, hydrochloric acid skin burns might have promoted the systemic inflammatory mediators' mechanism involved in the development of guttate psoriasis lesion's after the dermal injury.

Poisoning related to therapeutic error in prolonged low-dose methotrexate treatment.

AIMS: To study the predictive factors for the development of clinical manifestations in poisoning due to the erroneous taking of low-dose methotrexate (MTX). METHODS: A retrospective observational study was performed. Only cases of erroneous administration in non-oncologic outpatients were included (July 2008-March 2020). RESULTS: Forty-one cases were included. All patients were taking MTX for the first time. In 36 cases, patients took MTX daily instead of weekly. In the other five patients, MTX was sold instead of methylergometrine. Clinical manifestations were absent in 12/41 patients (29.3%). All 29 (70.7%) symptomatic patients recognized the medication error when they developed clinical manifestations: dermatological, haematological and gastrointestinal symptoms. Statistical results showed that symptomatic patients were older, received a higher amount of total dose and were treated for longer. Moreover, the probability of being symptomatic increases as a function of age and of total dose. Asymptomatic patients were treated with folinic acid (30 mg/m2 /day) for 5 days. Symptomatic patients were treated with folinic acid together with treatments for the specific clinical manifestations. No patients were treated with glucarpidase. All patients fully recovered. CONCLUSIONS: When MTX is prescribed for the first time, it is important to clearly communicate with patients to avoid therapeutic errors. In our experience, age, total dose taken and number of days of assumption are predictive for the presence/absence of clinical manifestations. These parameters must be evaluated together to identify patients needing maximum starting treatment with folinic acid and closer monitoring.

Exposure to Nail and False Eyelash Glue: A Case Series Study.

The use of artificial nail tips in professional manicure services and the application of false eyelashes are a growing trend among young women. Often, this "beauty routine" is performed at home without the supervision of an expert beautician, raising health problems due to either the spillage of these products or to accidental exposure to children. The aim of this study is to review the Pavia Poison Control Centre clinical records to identify the frequency, the most common route of exposure, and the possible risks associated to these events to support the decision-making process in emergency departments. The Pavia Poison Control Centre database was retrospectively searched for records reporting nail or false eyelash glue exposure from January 2007 to April 2020, and 42 patients were identified. Among the patients, 76% presented symptoms from mild to severe, while 24% were asymptomatic. The most common route of exposure was dermal, through cutaneous contact, as determined for 19 patients involved. Among these, seven patients presented with second-degree chemical burns, cutaneous erythema, and ocular symptoms. The most dangerous glue component was cyanoacrylate, leading to symptoms in 16 out of 22 patients, while three cases remained asymptomatic. Even if this exposure is relatively rare, nail and false eyelash glue can be seriously harmful, especially when exposure occurs via dermal or ocular routes. In the case of emergency, it is important to treat the patient as fast as possible to limit the damage caused by a burn. Moreover, even though these products are often perceived as harmless, safety precautions should be taken to prevent children from accidental contact.

Latrodectism in Italy: First report of successful treatment of L. tredecimguttatus envenomation using L. mactans antivenom from North America.

INTRODUCTION: Latrodectism is a rare, but potentially severe, clinical syndrome caused by spider of the genus Latrodectus. L. tredecimguttatus is widespread in Italy and its bite cause the injection of α-latrotoxin that cause depletion of acetylcholine at motor nerve endings and release of catecholamines at adrenergic nerve endings. We describe the first clinical case of L. tredecimguttatus poisoning successfully treated with L. mactans antivenom from North America. CASE REPORT: A healthy 60-year-old patient was admitted to the emergency department after unknown insect sting or arachnid/snake bite. In the early morning, the patient was working in the countryside when he felt a sting-like pain in the medial area of the right lower leg, associated with an intense burning sensation. An hour later he developed agitation, hoarseness, sweating, abdominal distress and intense pain in his right leg. In the emergency room vital signs showed a hypertensive crisis, tachycardia and peripheral oxygen desaturation. ECG was normal and ABE showed mixed acid-base disorder. Blood tests showed leukocytosis with neutrophilia, high levels of myoglobin, with normal coagulation and normal plasmatic cholinesterase. Neck, thorax and abdomen CT scan, with and without contrast medium, was negative. Four hours after admission hypertension worsened with board like rigid abdomen and onset of fasciculations, tremors, miosis and intense regional sweating. The definitive diagnosis of poisoning by L tredecimguttatus was based on the clinical picture. Within short time the antidote was provided by the Poison Centre and administered. A marked improvement of the symptomatology was noted after 30 minutes, and 1 hour later all symptoms were under control. The patient was discharged after 2 days. CONCLUSIONS: The clinical presentation of a patient suffering from latrodectism places the clinician in front of a challenging differential diagnosis. Following the suspicion, the first-line doctor is invited to discuss the case with a toxicologist, in order to confirm or exclude the diagnosis and implement all therapeutic measures. In our clinical case, the absence of organic lesions, laboratory tests not suggestive for other causes, and the presence of typical clinical feature suggested the diagnosis of L tredecimguttatus poisoning. This hypothesis was then supported by the close temporal relation between antivenom administration and symptoms improvement. With this case, we report the first use of L mactans antivenom from North America to treat L.tredecimguttatus poisoning and we confirm its effectiveness in counteracting latrodectism caused by this spider.

A new, sensitive and versatile assay for quantitative determination of α-fluoro-ß-alanine (AFBA) in human urine by using the reversed-phase ultrahigh performance-tandem mass spectrometry (rp-UHPLC-MS/MS) system.

A method for the quantitation of α-fluoro-ß-alanine (AFBA), the main metabolite of capecitabine (Cape) and 5-fluoruracil (5-FU), is described. Among antineoplastic drugs (ADs), 5-FU and Cape (the new oral prodrug) are the most commonly applied drugs in cancer therapy. The main objective of this study was to develop a reliable method that would be easy to run on a reversed-phase UHPLC system coupled to tandem mass spectrometry. AFBA was derivatized with Sanger's reagent to ensure complete yield of a stable 2,4 dinitrophenil-α-fluoro-ß-alanine derivative. This method was based on the use of a mixed-mode anion exchange solid phase extraction enabling urinary extracts to be clear of endogenous interferences affecting quantitative results. The assay was validated in human urine according to FDA criteria with the use of a labeled internal standard (ß-alanine-d4) to minimize experimental error. Good accuracy and precision were demonstrated by determining spiked urine QC samples in four consecutive days. The recovery of AFBA was between 70.0 and 82.6%, with a matrix effect that was 12.8%-18.5%. The lower limit of quantitation (LOQ) was 0.5 ng/mL with a coefficient of variation of 5.3%. This assay was successfully applied to determine the levels of this metabolite in a large number of urine samples taken from personnel who were occupationally exposed to ADs.

Intentional ingestion of elemental mercury requiring multi-step decontamination and prophylactic appendectomy: a case report and treatment proposal.

BACKGROUND: Ingestion of elemental mercury (Hg0) is considered non-toxic. After massive ingestion, local intestinal complications may develop: retention within appendix is quite frequent but treatment is debated. We describe a case of intentional ingestion of Hg0 requiring multi-step decontamination and prophylactic appendectomy. Case detail: A 19-year-old woman was admitted to ED for abdominal pain. History revealed ingestion of large amount of Hg0 as suicide attempt. To prevent absorption, facilitate elimination, and avoid complications a conservative approach was started. Due to inefficacy of initial maneuvers colonoscopy with irrigation/aspiration was performed, repeated whole bowel irrigation was continued and second colonoscopy was performed to clean residual metal. Abdominal plain films confirmed the presence of retained mercury within the appendix in asymptomatic patient. To reduce risk of appendicitis, potential perforation, and possibly systemic toxicity, a prophylactic laparoscopic appendectomy was performed at day 5 with removal of all retained mercury without peritoneal spillage. Highest mercury concentration was 22.7 mcg/L in serum (1-4.5 mcg/L) and 5.1 mcg/L in urine (0.1-5 mcg/L). CONCLUSIONS: After ingestion, metal retention in appendix is quite frequent. Evidence about optimal treatment are different and based on case reports. A multi-step approach with multidisciplinary evaluation tailored to the patient is suggested.