Swanson LD, Hommerding HA, Schmid RD
… +1 more, Hovda LR
J Med Toxicol
· 2025 Jul · PMID 40259165
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INTRODUCTION: Pet Poison Helpline (PPH), a 24/7 international animal poison control center has observed a significant and rising number of exposures detailing multisystemic signs and adverse outcomes associated with ocla...INTRODUCTION: Pet Poison Helpline (PPH), a 24/7 international animal poison control center has observed a significant and rising number of exposures detailing multisystemic signs and adverse outcomes associated with oclacitinib maleate (Apoquel) overdoses. METHODS: Pet Poison Helpline utilizes a proprietary electronic database which was retrospectively reviewed for oclacitinib maleate exposure information from January 2022 to November 2024 through their toxicology consultation service. RESULTS: Market entry and distribution of chewable oclacitinib maleate occurred in October 2023. In the year following, there was a 299% increase in calls to PPH from inadvertent exposure. Of the 417 symptomatic cases reviewed, 63 cases were symptomatic cats, and 354 cases were symptomatic dogs. Multi-system organ involvement, including neurological, gastrointestinal, cardiovascular, renal, hepatic, and ocular signs, as well as laboratory abnormalities were observed. DISCUSSION: Introduction of a chewable formulation in October 2023 likely attributed to a marked increase in exposures. Accompanying this rise in overdose exposures, a notable escalation in multisystemic effects was seen, including neurological, gastrointestinal signs, cardiovascular disturbances, ocular irregularities, renal and hepatic injury, and complete blood count (CBC) hematological abnormalities. Treatment is largely symptomatic and supportive therapy. CONCLUSION: The increased occurrence of exposures to oclacitinib maleate underscores necessity for additional research of JAK inhibitors in animals to better understand and address oclacitinib maleate toxicosis.
Herzel B, Batavia N, Gavaza P
… +7 more, Phan T, Samones E, Ruha AM, Furmaga J, Hoyte C, Wolk BJ, ToxIC Snakebite Study Group
J Med Toxicol
· 2025 Jul · PMID 40227519
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UNLABELLED: Envenomation is a global health issue, with over 9,000 encounters managed in the United States yearly. The introduction of immunoglobulin fragment antivenom has reduced the risk of hypersensitivity. This stud...UNLABELLED: Envenomation is a global health issue, with over 9,000 encounters managed in the United States yearly. The introduction of immunoglobulin fragment antivenom has reduced the risk of hypersensitivity. This study compares treatment costs of crotaline envenomation using the Fab and F(ab') antivenoms as reported to the North American Snakebite Registry (NASBR), a nationwide surveillance tool. METHODS: This was a retrospective analysis of NASBR data between 2018 and 2020. The following data points were assessed: patient demographics (age, gender, race), snake species, type of antivenom used, and treatment costs. Unit costs were estimated based on United States Centers for Medicare and Medicaid Services data. Average (mean) per patient costs from the payer perspective were calculated by multiplying resources by the unit costs. Sensitivity analyses were performed regarding cost variance and snake species. All costs reported in this study are in U.S. dollars. RESULTS: The average total cost of treatment was $31,343 per person, with medications contributing 72% of the total. Average total cost among patients who received Fab treatments was $33,347 per person compared to $19,747 among patients who received F(ab'). Antivenom costs accounted for 75% of the total cost in the Fab group and 42% in the F(ab') group. F(ab') required more vials than Fab (median 18 versus 10). Non-antivenom costs such as hospitalizations were higher in the F(ab') group. Using average sale prices increased average total cost to $52,572; Fab remained more expensive. CONCLUSION: Antivenom is the primary cost driver in snakebite treatment in North America. Treatment with F(ab') resulted in lower overall costs, driven by lower cost of antivenom. F(ab') did not significantly lower overall resource use except for blood product administration.
Spungen HH, Sherman JM, Ryan K
… +3 more, Krueger JJ, Levine M, Spyres MB
J Med Toxicol
· 2025 Jul · PMID 40214921
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INTRODUCTION: Although dihydropyridine calcium channel blockers (DHP CCBs) are considered to have less direct myocardial toxicity than non-dihydropyridines, DHPs remain a common cause of morbidity and mortality. We sough...INTRODUCTION: Although dihydropyridine calcium channel blockers (DHP CCBs) are considered to have less direct myocardial toxicity than non-dihydropyridines, DHPs remain a common cause of morbidity and mortality. We sought to examine various indices of critical illness and describe the clinical course of a population of DHP CCB-poisoned patients with special attention to vasopressor dosing and ischemic complications. METHODS: This is a retrospective chart review of DHP CCB exposures admitted to a single center. The study site was a single tertiary referral center with an in-house medical toxicology consultation/admitting service. Inclusion criteria included age ≥ 14 years and DHP ingestion noted on departmental patient log. Patients were excluded if DHP exposure was not documented in the medical record. The study period ranged from July 1, 2010 through December 31, 2022. Data on clinical presentation, management, and outcomes were reported. RESULTS: Sixty-eight cases of DHP exposure were analyzed; 87% were intentional ingestions. Amlodipine represented 88% of cases. 85% included cases involved co-ingestions. Vasopressors were administered in 42 cases (62%), with a median of three agents (IQR 1-4). Norepinephrine was most common (N = 41; 98%), followed by epinephrine (N = 23; 55%); median maximal rates were 45.0 (IQR 13.5-70.0) and 25.0 (IQR 12.0-30.0) mcg/min, respectively. 15% (N = 10) received high dose insulin-euglycemic therapy (HIE); all had > 2 vasopressors administered before administration of HIE. Twelve (18%) patients had ischemic complications; five (7%) experienced ischemic complications not evident before vasopressor administration. There were five deaths (7%). CONCLUSIONS: Multiple vasopressor use was common in this population of patients with DHP CCB toxicity. Despite the high doses of vasopressors used, temporally related ischemic complications were uncommon.
Counts CJ, Spadaro AV, Cerbini TA
… +8 more, Krotulski AJ, Walton SE, Greller HA, Nelson LS, Ruck BE, Hung O, Logan B, Calello DP
J Med Toxicol
· 2025 Apr · PMID 40102319
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BACKGROUND: Tianeptine, an atypical antidepressant not approved in the United States, is readily purchased from unregulated markets such as the internet and gas stations. We became aware of a cluster of 34 patients in Ne...BACKGROUND: Tianeptine, an atypical antidepressant not approved in the United States, is readily purchased from unregulated markets such as the internet and gas stations. We became aware of a cluster of 34 patients in New Jersey who became ill following ingestion of the tianeptine containing-product Neptune's Fix, the rate of which (4.6 cases per month) far exceeded the background rate for this substance of 0.5 cases per year. METHODS: We retrospectively identified tianeptine exposures reported to the New Jersey Poison Information and Education System (NJPIES) prior to June 2023 to determine the background rate of tianeptine exposure. From June 2023- February 2024 we prospectively surveilled tianeptine exposures reported to NJPIES, recorded demographic and clinical information, and recruited samples for testing. Six samples of the ingested products were obtained and analyzed using gas chromatography mass spectrometry (GC-MS) and liquid chromatography quadrupole time-of-flight mass spectrometry (LC-QTOF-MS). Whole blood samples from two patients were tested for tianeptine and synthetic cannabinoids. RESULTS: During the period of interest, NJPIES received 41 exposure calls, with 37 reporting acute toxicity in 34 unique patients, two reporting chronic tianeptine use, and two reporting withdrawal. Among the 37 exposures resulting in acute toxicity, commonly reported effects included altered mental status, tachycardia, hypotension, and seizures. 43% (n = 16) were intubated, and 65% (n = 24) were admitted to the ICU. Analytical testing of six samples identified variable product composition, containing various xenobiotics including tianeptine, kava alkaloids, natural cannabinoids, and the synthetic cannabinoids MDMB-4en-PINACA and ADB-4en-PINACA. MDMB-4en-PINACA was detected in one of the two patient blood specimens. CONCLUSIONS: These cases represent a marked increase in tianeptine exposures compared with the poison center's historical average. Analytical testing revealed variable product composition, including the presence of synthetic cannabinoids. Clinicians should be aware that tianeptine containing products are widely available, unregulated, and can be adulterated.
J Med Toxicol
· 2025 Apr · PMID 40053223
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The meeting abstract is an important step in the process of disseminating new knowledge. The invitation to present an abstract at a scientific meeting is the first opportunity for an investigator to showcase their findin...The meeting abstract is an important step in the process of disseminating new knowledge. The invitation to present an abstract at a scientific meeting is the first opportunity for an investigator to showcase their findings to an audience outside of their institution. The constructive feedback and generous insights from expert peers are valuable when preparing a manuscript for eventual submission to a journal. Knowing how to get the most out of a meeting abstract presentation is essential to scholars engaged in scientific discovery.
Ekaney ML, Pritt TA, Attal N
… +2 more, Murphy CM, McKillop IH
J Med Toxicol
· 2025 Apr · PMID 40014260
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INTRODUCTION: Acetaminophen (APAP) overdose remains a common cause of liver injury, primarily due to its toxic metabolite N-acetyl-p-benzoquinone imine (NAPQI). This study sought to investigate APAP-induced platelet aggr...INTRODUCTION: Acetaminophen (APAP) overdose remains a common cause of liver injury, primarily due to its toxic metabolite N-acetyl-p-benzoquinone imine (NAPQI). This study sought to investigate APAP-induced platelet aggregation in vitro, and the implication of CYP2E1 in the metabolism of APAP and hepatic cell toxicity. METHODS: Co-cultures of platelets and hepatic cells that do not (HepG2) and do express CYP2E1 (HepG2) were exposed to APAP (0-20 mM), NAPQI (0-250 µM), APAP in the absence/presence of inhibitors of glutathione (50 μM buthionine sulphoximine (BSO)), or APAP in the absence/presence of inhibitors CYP2E1 (chlormethiazole (CMZ, 100 µM), or 4-methylpyrazole (4-MP, 5 mM)). Platelet aggregation, cell viability and reactive oxygen species (ROS) were analyzed. Changes in platelet aggregation was determined in platelets directly exposed to APAP/NAPQI. RESULTS: Exposure to APAP decreased platelet aggregation under co-culture conditions but not in platelet-only cultures. Conversely, NAPQI exposure decreased platelet aggregation in both co-culture and platelet-only conditions. Both APAP and NAPQI reduced cell viability in HepG2 and HepG2 cells, with BSO enhancing APAP toxicity, while 4-MP mitigated it. Acetaminophen exposure led to ROS production in HepG2 cells, with no effect of CMZ and 4-MP. CONCLUSIONS: Acetaminophen exposure impacts platelet aggregation in co-cultures of platelets and HepG2/HepG2 cells with increased ROS production in HepG2 cells and 4-MP preventing APAP-induced cytotoxicity in HepG2 cells. While APAP had no direct effect on platelets, NAPQI exposure acted to decrease platelet aggregation. These findings enhance our understanding of the mechanisms of APAP-induced hepatotoxicity and the potential role of APAP-induced hepatocellular toxicity in platelet aggregation.
Goldfine CE, Carpenter JE, Mazer-Amirshahi M
… +2 more, Dunavin A, Abston S
J Med Toxicol
· 2025 Apr · PMID 40000580
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These are the selected abstracts for the 2025 American College of Medical Toxicology (ACMT) Annual Scientific Meeting, which will take place from April 4-6, 2025, in Vancouver, Canada. This year's accepted abstracts incl...These are the selected abstracts for the 2025 American College of Medical Toxicology (ACMT) Annual Scientific Meeting, which will take place from April 4-6, 2025, in Vancouver, Canada. This year's accepted abstracts include original research studies, including contributions from the Toxicology Investigators Consortium (ToxIC), and clinically significant case reports highlighting unique toxicologic phenomena. These presentations reflect the continued growth and impact of toxicology research, providing attendees with valuable insights into emerging trends, novel treatment strategies, and evolving best practices in the field.
Berger JC, Severe AD, Jalloh MS
… +1 more, Manini AF
J Med Toxicol
· 2025 Apr · PMID 39904921
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INTRODUCTION: Nitazene compounds are high potency, synthetic opioids, recently detected in the United States illicit opioid supply. This is a scoping review to summarize the available body of literature on naloxone and h...INTRODUCTION: Nitazene compounds are high potency, synthetic opioids, recently detected in the United States illicit opioid supply. This is a scoping review to summarize the available body of literature on naloxone and hospitalization reports in response to nitazene compound overdose. METHODS: This review adhered to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) extension for Scoping Reviews. PubMed, ProQuest, and Google Scholar were accessed. Articles were limited to full-text peer-reviewed publications appearing in scholarly journals between January 2018 and December 2024. Total naloxone dose (in mg, primary outcome) and total length of stay (LOS, in hours, secondary outcome) were recorded. RESULTS: Of 109 articles screened, 103 were excluded (44 non-human; 35 no nitazene exposure, 9 no naloxone administered, 9 post-mortem data only, 3 non-overdose, 2 non-English, and 1 full text unavailable), leaving 6 articles included. Data were described on 19 distinct patients with nitazene compound overdose (meto-, isoto-, proto-, and eto-nitazene), all of whom had naloxone data, and 10 of whom had LOS data. Median total naloxone doses were the following: metonitazene 6.00mg; etonitazene 3.06mg; isotonitazene 3.00mg; protonitazene 1mg (p=0.4). Mean hospital LOS were the following: metonitazene 360 hours; etonitazene 122.25 hrs; isotonitazene 32.67 hrs; protonitazene 20 hrs. CONCLUSION: This scoping review reveals a paucity of data on nitazene compound overdoses and identifies a gap in our current opioid crisis response. Most nitazene cases reviewed involved hospitalization, had high naloxone dosing, and relatively long LOS. Differences in naloxone dose and hospital LOS could underscore the unpredictable and potent nature of these substances.
Thompson TR, Hays HL, Kistamgari S
… +4 more, Rine NI, Zhu M, Xiang H, Smith GA
J Med Toxicol
· 2025 Apr · PMID 39890754
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INTRODUCTION: This study investigated the characteristics and trends of pediatric exposures to caffeine energy products reported to US poison centers METHODS: National Poison Data System data for caffeine energy product...INTRODUCTION: This study investigated the characteristics and trends of pediatric exposures to caffeine energy products reported to US poison centers METHODS: National Poison Data System data for caffeine energy product single-substance exposures during 2011-2023 among individuals < 20 years old were analyzed. RESULTS: There were 32,482 caffeine energy product exposures reported to US poison centers with a 17.3% exposure rate increase during 2011-2023. Most exposures were among < 6-year-olds (69.6%), males (56.7%), or involved liquid formulations (57.5%). Most (80.7%) were not treated in a healthcare facility; however, 1.6% were medically admitted. Teenagers 13-19 years old were more likely to be medically admitted (OR = 12.74, 95% CI: 10.40-15.60) or have a serious medical outcome (OR = 18.83, 95% CI: 16.88-21.01) than children < 13 years old. Solid energy product formulations were more likely to be associated with a serious medical outcome (OR = 1.98, 95% CI: 1.81-2.17) or medical admission (OR = 5.23, 95% CI: 4.31-6.36) than other types of formulations. During the study period, exposure rates increased for liquid (34.5%) and powder/granules (632.9%) product formulations but decreased for solids (-51.5%). Among liquid formulation subcategories, the exposure rate for beverages increased (46.5%) and that for shots decreased (-86.1%). CONCLUSIONS: Although most pediatric exposures to caffeine energy products reported to US poison centers were associated with no or minimal clinical effects, serious medical outcomes and medical admissions occurred. The product formulations that drove the 17% increase in the exposure rate changed during the study period. Opportunities exist to reduce the adverse effects of caffeine energy products among the pediatric population.