Labetalol is widely prescribed as a first-line antihypertensive in pregnancy; however, rare but potentially severe idiosyncratic hepatotoxicity has been reported, with a disproportionately strong reporting signal for liver injury relative to other β-blockers. In this report, a fatal case is described in which mild initial symptoms rapidly progressed to fulminant hepatocellular injury and acute liver failure within days, underscoring the importance of early recognition of drug-induced liver injury and prompt discontinuation of labetalol. A PRISMA-guided systematic review of MEDLINE, Embase, CINAHL, Cochrane Library, PubMed, and Google Scholar (from inception to December 2025) identified 27 published case reports. Patients were predominantly female (≈80%), and one-third were pregnant or postpartum. Latency ranged from 7 to 365 days (median ≈60 days). The injury phenotype was consistently hepatocellular, often with autoimmune-like serologic or histologic features. Outcomes included full recovery in most (≈75%), but also liver transplantation and death. In the FDA Adverse Event Reporting System (2020Q1-2025Q1), labetalol showed strong disproportionality signals for DILI (PRR 22.7, 95% CI 15.6-33.1; ROR 23.7, 95% CI 16.0-35.1; IC025 2.5) and autoimmune hepatitis (PRR 59.8, 95% CI 34.1-104.8; ROR 60.9, 95% CI 34.4-108.1; IC025 2.8), which persisted when restricted to other β-blockers as comparators. Signals for acute hepatic failure and hyperbilirubinemia were elevated but less statistically robust. The available evidence is consistent with a clinically meaningful and biologically plausible association between labetalol and idiosyncratic hepatotoxicity, supporting heightened clinical awareness and further mechanistic and population-based study.

Using zebrafish (Danio rerio) as a model organism, we studied metabolomic markers of β-blocker neurotoxicity (propranolol, metoprolol, bisoprolol) and the relationships between neurotransmitter disturbances (dopamine, epinephrine, choline, cortisol) and their effects. Propranolol produced the most pronounced changes: significant increases in cortisol and epinephrine and decreases in dopamine and serotonin levels. Metoprolol caused a moderate increase in cortisol while elevating serotonin, suggesting a more balanced pharmacological profile. Bisoprolol had virtually no effect on cortisol or monoamine levels but increased the concentrations of choline, glycine, and glutamate. Differences in neurometabolic effects of β-blockers were identified: propranolol demonstrated a strong neurotoxic potential, consistent with its depressive side effects in humans; metoprolol showed an intermediate effect; while bisoprolol did not affect CNS. Zebrafish exhibited high sensitivity to neurochemical shifts, making this model valuable for preclinical drug neurotoxicity assessment.

Allergy to venoms of stinging insects (bees, yellow jackets, hornets, wasps, and stinging ants) causes large local reactions or systemic reactions, including anaphylaxis. Diagnostic evaluation includes skin testing and/or serum venom-specific IgE and basal serum tryptase (to identify underlying mast cell disorders). Patients with sting anaphylaxis should be prescribed epinephrine and venom immunotherapy which prevents allergic reactions in up to 98% of patients. Most patients may safely discontinue venom immunotherapy after 5 years, although high-risk patients need to continue indefinitely. Further research is needed to improve the predictive value of diagnostic testing and the safety and efficacy of treatment.

In the current poly-drug use context, the contribution of each detected drug to the cause of death in a fatal poisoning may be difficult to assess. In this study, we aimed to investigate whether the analysis of drug paraphernalia found at the death scene could assist in the cause-of-death determination. Over a period of about four years, drug paraphernalia were analysed whenever paraphernalia was available for the analysis and a drug-related death was suspected. A total of 134 syringes and other kinds of paraphernalia were analysed in 77 death cases. Amphetamine, buprenorphine, and alprazolam were the most common findings. One single substance was detected in 51% of the analysed items, but some items contained up to 5 different substances, typically amphetamine or buprenorphine together with a benzodiazepine. Of the cases in which drug paraphernalia were analysed, in 57%, at least one detected substance was finally implicated as the cause of death in fatal poisonings, and in 14%, the detected substance was assessed as a contributing factor to death. Analysis of drug paraphernalia generated completely new drug findings in only a few cases. Comparing the results of the analysis of drug paraphernalia recovered at the death scene with the results of post-mortem toxicology allows for better understanding of circumstances of death, and in some cases enables more accurate determination of the cause of death by identifying the freshly administered drugs. In cases with new psychoactive substances, the analysis of paraphernalia can provide information that could otherwise be difficult to obtain as the concentrations in biological samples can be low.

BACKGROUND Anaphylaxis is a severe, systemic hypersensitivity reaction that poses a potential threat to life. The occurrence of mastocytosis increases the likelihood of severe anaphylactic reactions. Appropriate management is crucial for improving clinical outcomes. CASE REPORT The case describes severe anaphylactic shock in a 31-year-old female patient with suspected mastocytosis. The shock occurred following a sting by a hymenopteran insect. The patient required mechanical ventilation and circulatory support for cardio-respiratory failure. Because of insufficient response to intramuscular injections of epinephrine, continuous intravascular infusion was needed. Intensive fluid therapy with balanced crystalloids was administered. As part of supportive treatment, antihistamines (rupatadine via a nasogastric tube) and intravenous glucocorticosteroids were given. Acid-base disturbances were also corrected. The patient was discharged from the intensive care unit on the third day of hospitalization in good general condition. CONCLUSIONS The core management of anaphylaxis in a patient with suspected or diagnosed mastocytosis is similar to the general recommendations for anaphylaxis treatment. However, it should be noted that patients with mastocytosis can have significantly higher requirements for adrenaline. Continuous intravenous infusion of adrenaline during the first 1 to 2 days following the onset of anaphylaxis may be warranted. Due to the rapid course of anaphylaxis and excessive immune response, more severe disturbances in organ perfusion can occur, resulting in metabolic acidosis. In such patients, intravenous infusion of sodium bicarbonate can be necessary. Therefore, patients with mastocytosis who experience anaphylaxis may be less responsive to epinephrine and should be admitted to the intensive care unit early.

Somatostatin-expressing low-threshold spiking interneurons (SOM-INs) constitute a key inhibitory population in the dorsal striatum, yet their contribution to parkinsonian states and L-DOPA-induced dyskinesia (LID) remains poorly understood. Here, we combined in vivo behavioral assays, chemogenetics, and ex vivo electrophysiology to examine how nigrostriatal dopamine loss and dopaminergic therapy shape SOM-INs' activity and function. During LID, SOM-INs displayed increased c-Fos expression, revealing their recruitment during dyskinetic states. Patch-clamp recordings showed that SOM-INs in control mice fire tonically with characteristic abrupt pauses. While their firing patterns are preserved after dopamine depletion and L-DOPA therapy, dopamine depletion shifted their interspike interval distribution toward longer intervals, indicating reduced intrinsic activity. This deficit was partially reversed by chronic L-DOPA. Consistent with their expression of Drd1/Drd5 transcripts, SOM-INs were excited by the D1/D5 receptor agonist SKF81297 across groups. Chemogenetic inhibition experiments revealed a functional role for SOM-INs in early rotarod learning, demonstrating their contribution to motor skill acquisition, but did not affect baseline motor output in sham or parkinsonian mice. Moreover, SOM-IN inhibition during chronic L-DOPA treatment modestly but consistently exacerbated LID expression selectively during the wearing-off phase, without altering parkinsonian symptoms or the therapeutic efficacy of L-DOPA. Notably, SOM-IN inhibition did not modify the long-duration antiparkinsonian response that persisted after discontinuing L-DOPA. Together, these findings identify SOM-INs as an intrinsically active striatal interneuron population whose excitability is shaped by dopamine depletion and dopamine receptor stimulation, and whose activity restrains dyskinetic responses to dopaminergic overstimulation. Their selective influence on dyskinesia, but not on the therapeutic actions of L-DOPA, highlights SOM-INs as a potential target for circuit-level interventions aimed at improving the motor side-effect profile of dopaminergic therapies.

Methamphetamine (METH) is a widely abused psychostimulant known to induce neurotoxicity through oxidative stress and apoptosis. Sulforaphane (SFN), a natural compound found in cruciferous vegetables, has shown neuroprotective potential, but its role in METH-induced neuronal injury remains unclear. In this study, we integrated network pharmacology together with in vitro and in vivo experiments to investigate the protective effects of SFN and its underlying mechanisms. A total of 235 overlapping targets were identified between SFN and METH-related neurotoxicity, with significant enrichment in apoptosis and the PI3K/AKT signaling pathway. Molecular docking suggested a potential interaction between SFN and AKT1 with favorable binding affinity. In HT22 hippocampal neuronal cells, SFN significantly improved cell viability, restored the Bcl-2/BAX ratio, inhibited caspase-3 activation, and reduced nuclear damage caused by METH. These protective effects were associated with increased phosphorylation of PI3K and AKT, and were markedly diminished by the PI3K inhibitor LY294002. In a METH-induced neurotoxicity mouse model, SFN ameliorated hippocampal histopathological damage, reduced TUNEL-positive apoptotic cells, and normalized the expression of BAX, Bcl-2, cleaved caspase-3, and phosphorylated PI3K/AKT. These findings suggest that SFN alleviates METH-induced neurotoxicity by activating the PI3K/AKT pathway and inhibiting mitochondria-dependent apoptosis, providing evidence for its potential as a therapeutic candidate for METH-related neuronal injury.

Chemsex refers to the use of psychoactive substances, such as GHB, methamphetamine, and poppers, to enhance sexual experiences, predominantly among men who have sex with men and transgender individuals in LGBT+ communities. The practice is associated with increased risks, including sexually transmitted infections, substance dependence, overdose, and cardiac arrest. We present a fatal case of cardiac arrest following chemsex, where high levels of GHB and methamphetamine were detected. This highlights the severe health consequences and the need for targeted support and harm reduction strategies.

Synthetic cathinones (SC) are a class of psychoactive stimulants structurally similar to amphetamines. Despite a high prevalence of SC detection in emergency department (ED) drug surveillance in Taiwan, detailed reports of SC-related fatalities and their acute clinical course in the emergency medicine literature are limited. This case series describes the presentations, clinical course, and outcomes of four fatal SC-associated intoxications, highlighting critical emergency management insights.