Negative Toxicology Research Articles

Does Topiramate Add-On Enhance the Response to the MATRIX Program in Individuals with Methamphetamine Use Disorder? A Double-Blinded Randomized Placebo-Controlled Trial

Background: Methamphetamine dependence significantly impacts individuals and society. Treating methamphetamine use disorder is challenging due to limited evidence on effective pharmacotherapies and their interaction with nonpharmacologic interventions. This study evaluated the efficacy of topiramate compared to placebo in treating methamphetamine use disorder among participants in a Matrix program. Methods: Participants were recruited from the Addiction Center of Iran Psychiatric Hospital between January 2020 and June 2023 and randomly assigned to receive either topiramate or a placebo for 12 weeks, alongside Matrix program sessions. Blinding was maintained for participants, personnel, outcome assessors, and statisticians. Main outcomes included craving, desire to use, positive urine amphetamine toxicology rates, and depression severity. Craving was assessed using the Visual Analog Scale (VAS) and the Substance Craving Questionnaire–brief (SCQ-B). The desire to use was evaluated with the Addiction Severity Index (ASI), while depression severity was measured using the Beck Depression Inventory. Data analysis utilized IBM SPSS Statistics® 20.0, employing various statistical tests for comparison. Results: Both groups exhibited improvement in craving as per VAS scores (p=0.007), with greater reduction in the topiramate group; however, no significant difference was found between groups (p=0.06). The negative urine toxicology rates showed no significant difference (Hazard ratio=1.15, 95% CI: 0.75, 1.78). Depression scores decreased in both groups without significant between-group differences (p=0.78). Conclusion: The findings do not support the efficacy of topiramate in enhancing outcomes within a Matrix program for individuals with methamphetamine use disorder.

8158 Transient Blindness In Metformin-Associated Lactic Acidosis

Abstract Disclosure: Y. Abouelkheer: None. A. Nasir: None. M. Ibrahem: None. Transient Blindness in Metformin-associated Lactic Acidosis Background: Metformin-associated lactic acidosis (MALA) is a rare side effect of metformin use. MALA can result in acute transient blindness in patients with severe metabolic derangements. Clinical Case: A 62-year-old woman presented with severe diarrhea, poor oral intake, malaise, and vomiting on a background of metformin-treated type 2 diabetes mellitus. Laboratory investigations showed bicarbonate <2 mmol/L, anion gap 48 mmol/L, lactic acid 20.5 mmol/L, serum osmolality 352 mOsm/kg, negative urine toxicology screen, and positive SARS-CoV-2. In the emergency department, the patient developed sudden onset bilateral vision loss. The examination was remarkable for complete vision loss bilaterally in all fields, associated with minimally reactive pupils and spontaneous ocular movements with an otherwise unrevealing neurological examination. Computed Tomography (CT) of the brain with stroke protocol showed no evidence of acute intracranial process. CT angiogram of the brain and neck showed patent intracranial and cervical vasculature without high-grade stenosis, large vessel occlusion, or aneurysm. While receiving medical management with intravenous fluid resuscitation and sodium bicarbonate supplementation, the patient had a spontaneous return of vision with no additional neurological complications or deficits. The severe metabolic derangements were associated with distributive shock, requiring admission to the intensive care unit for urgent hemodialysis, pressor support, empiric antibiotics, and stress-dose steroids. Shortly after the patient’s only hemodialysis session, we noted the resolution of her critical metabolic disturbances, renal failure, and shock state. Laboratory investigations post-dialysis showed bicarbonate 12 mmol/L, anion gap 36 mmol/L, and lactic acid 10.5 mmol/L. Follow-up MRI showed chronic lacunar infarct of the left basal ganglia, and she was discharged home six days later. Conclusion: Transient blindness in MALA can mimic acute neurovascular events. Prompt correction of metabolic derangements can aid in reversing systemic symptoms and blindness. Reference: DeFronzo R, Fleming GA, Chen K, Bicsak TA. Metformin-associated lactic acidosis: Current perspectives on causes and risk. Metabolism. 2016;65(2):20-29. doi:10.1016/j.metabol.2015.10.014 Presentation: 6/2/2024

6978 Traumatic Presentation Of A Pancreatic Neuroendocrine Tumor

Abstract Disclosure: C.J. Kahn: None. J. Mai: None. A.E. Cabrera: None. A.D. Anderson: None. D.H. Huynh: None. Background: Insulinomas are a subset of functional pancreatic neuroendocrine tumors associated with neuroglycopenic symptoms, fasting hypoglycemia, and rapid resolution of symptoms with glucose administration. Despite this classic presentation, patients often spend years undiagnosed before formal diagnosis and definitive management. Clinical Case: We report the case of a 37-year-old post-partum female with a history of gestational diabetes who presented to our trauma center after losing consciousness while driving and colliding with a utility pole. Emergency Medical Services reported seizure-like activity on the scene with altered sensorium. Her initial blood glucose level of 32 mg/dL improved to 100 mg/dL after 100 ml of 10% dextrose. Initial biochemical analysis obtained from the trauma bay demonstrated a negative serum ethanol level, negative urine toxicology and sulfonylurea level, and elevated C-peptide of 6.71 ng/mL. After stabilization, she underwent a 72-hour fasting test. At the 12-hour mark, she developed hypoglycemia (blood glucose 36 mg/dL) correlated with elevated insulin (28.8 mU/L), proinsulin (173.1 pmol/L), and C-peptide (7.86 ng/mL). Although an initial CT scan of the abdomen and pelvis did not demonstrate any pancreatic abnormalities, an abdominal MRI demonstrated a 13 mm lesion in the tail of the pancreas consistent with a pancreatic neuroendocrine tumor. She subsequently underwent a laparoscopic distal pancreatectomy during the same hospital admission and recovered expeditiously. Final pathology demonstrated a 10 by 15 mm, grade two, well-differentiated neuroendocrine tumor with negative margins. The specimen stained strongly positive for synaptophysin and chromogranin, consistent with the clinical diagnosis of insulinoma. During the patient's postoperative recovery, she had no further episodes of hypoglycemia and did not require insulin for post-pancreatectomy hyperglycemia. She was discharged home with a glucometer and a follow-up scheduled with endocrinology and general surgery. Conclusion: The presentation of patients with insulinomas can vary from vague, nonspecific symptoms to altered levels of consciousness placing patients in potentially lethal situations. Moreover, the insulin resistance experienced by pregnant patients may mask clinical manifestations of hypoglycemia during the peripartum period, making diagnosis more elusive for this population. A high index of suspicion along with prompt diagnosis, in this case, led to definitive surgical management, effectively preventing future traumatic incidents secondary to hypoglycemia. Reference: 1. Dobrindt EM, Mogl M, Goretzki PE, Pratschke J, Dukaczewska AK. Insulinoma in pregnancy (a case presentation and systematic review of the literature). Rare Tumors. 2021;13. doi:10.1177/2036361320986647 Presentation: 6/3/2024

Proarrhythmic drugs, drug levels, and polypharmacy in victims of sudden arrhythmic death syndrome: An autopsy-based study from Denmark

BackgroundSudden arrhythmic death syndrome (SADS), characterized by an unknown or inconclusive cause of death at autopsy together with a negative or nonlethal toxicology screening result, is the most common cause of sudden cardiac death in victims younger than 35 years. The complete causality of SADS remains unclear, with drugs being a potential risk factor. ObjectiveThis study aimed to describe the toxicologic profiles of SADS victims, focusing on proarrhythmic drugs, drug levels, and polypharmacy. MethodsAll deaths in Denmark of those aged 1–35 years in 2000–2019 and 36–49 years in 2007–2019 were examined through death certificates, national registries, and autopsy reports with toxicology screenings. We investigated all sudden unexpected death victims with an autopsy performed, including negative or nonlethal drug findings, where cause of death was unknown or inconclusive (SADS). ResultsWe identified 477 SADS victims; 313 (66%) had a positive toxicology screening result (adjudicated nonlethal), with an average of 2.8 drugs per case. More than half of the SADS victims with a positive toxicology screening result had QT-prolonging or brugadogenic drugs present. Polypharmacy was present in 66%, psychotropic polypharmacy in 37%, and QT-prolonging polypharmacy in 22%, with the most frequent overall and QT-prolonging drug combination being an antipsychotic and a psychoanaleptic drug. QT-prolonging drugs were more often present at suprapharmacologic levels than non–QT-prolonging drugs. ConclusionThe majority of the SADS population had a positive toxicology screening result, with a notably large proportion having proarrhythmic drugs and polypharmacy. This highlights the need for future focus on drugs as a risk factor for SADS.

Toxicology Screening in Sports-Related Sudden Cardiac Death: A Multinational Observational Study

BackgroundKnowledge of toxicological findings among sports-related sudden cardiac death (SrSCD) is scarce. ObjectivesThis study aimed to describe postmortem toxicology findings in a multinational cohort of young SrSCD. MethodsPatients with sudden cardiac death (SCD) aged 12 to 49 years with a complete post mortem were included from Denmark, Spain, and Australia. Postmortem findings were compared between SrSCD and non-SrSCD, and toxicology findings in SrSCD were assessed. ResultsWe included 3,189 SCD, of which 219 (7%) were sports-related. SrSCD patients were younger (36 years vs 41 years; P < 0.001) and of male predominance (96% vs 75%; P < 0.001), and their death was more often caused by structural cardiac disease (68% vs 61%; P = 0.038). Positive toxicology screenings were significantly less likely among SrSCD than non-SrSCD (12% vs 43%; P < 0.001), corresponding to 82% lower odds of a positive toxicology screening in SrSCD. Patient characteristics were similar between SrSCDs with positive and negative toxicology screenings, but deaths were more often unexplained (59% vs 34%). Nonopioid analgesics were the most common finding (3%), and SCD-associated drugs were detected in 6% of SrSCD. SUD was more prevalent among the SrSCD with positive toxicology (59% vs 34%). ConclusionsSports-related SCD mainly occurred in younger men with structural heart disease. They had a significantly lower prevalence of a positive toxicology screening compared with non-SrSCD, and detection of SCD-associated drugs was rare.

Abstract 18940: Can the Religious Observation of Fasting Cause Prinzmetal’s Angina?

CASE DESCRIPTION: A 73-year-old male with HTN, HLD, CAD/MI status post PCI to the RCA and LAD (2021), and former tobacco use presented with acute, severe, left-sided chest pain with nausea, diaphoresis and dizziness. He started fasting and adjusted his sleep schedule 3 days prior for Ramadan, but did not miss any of his medications including isosorbide and ranolazine. He was chest pain free on arrival, but subsequently developed severe chest pain becoming bradycardic, hypotensive and hypoxic. At that time the EKG (Figure 1) showed ST elevation (STEMI) in leads II, III and aVF with high degree atrioventricular block. He was started on intravenous fluids and a vasopressor but had spontaneous resolution of symptoms within 10 minutes. Emergent coronary angiography revealed stable 70% stenosis of an ostial left circumflex (LCx) artery and non-obstructive CAD of the RCA. Labs revealed normal blood glucose, negative urine toxicology and mild elevation of troponin (trended serially). Echocardiogram was normal with no regional wall motion abnormalities. He was treated as vasospastic angina with addition of a calcium channel blocker without recurrence of his symptoms. DISCUSSION: Vasospastic angina is an important cause of acute coronary syndrome. Our patient had severe vasospastic angina while being treated for CAD for over 10 years. No prior studies have linked fasting to vasospasm. We hypothesize that fasting and a diurnal sleep schedule may contribute to worsened episodes in susceptible individuals due to hormonal changes including glucose shifts and an increase in catecholamines and cortisol. Increased catecholamine levels may induce spasm by stimulation of alpha receptors in the coronary arteries, and cortisol can induce vascular inflammation, potentiating negative effects. We highlight the importance of keeping high clinical suspicion for a diagnosis of vasospasm, as well as the need to further understand the complex pathophysiology to counsel patients in the future.

Amphetamine Positivity Prior to Burn Surgery Does not Adversely Affect Intraoperative Outcomes.

The treatment of burn patients using amphetamines is challenging due hemodynamic liabilty and altered physiology. Wide variation exists in the operative timing for this patient population. We hypothesize that burn excision in patients admitted with amphetamine positivity is safe regardless of timing. Data from two verified burn centers between 2017 and 2022 with differing practice patterns in operative timing for amphetamine-positive patients. Center A obtains toxicology only on admission and proceeds with surgery based on hemodynamic status and operative urgency, whereas Center B sends daily toxicology until a negative test results. The primary outcome was the use of vasoactive agents during the index operation, modeled using logistic regression adjusting for burn severity and hospital days to index operation. Secondary outcomes included death and inpatient complications. A total of 270 patients were included, and there were no significant differences in demographics or burn characteristics between centers. Center A screened once and Center B obtained a median of four screens prior to the surgery. The adjusted OR of requiring vasoactive support intraoperatively was not associated with negative toxicology result (P = .821). Having a body surface area burned >20% conferred a significantly higher risk of vasoactive support (adj. OR 13.42 [3.90-46.23], P < .001). Mortality, number of operations, stroke, and hospital length of stay were similar between cohorts. Comparison between two verified burn centers indicates that waiting until a negative amphetamine toxicology result does not impact intraoperative management or subsequent burn outcomes. Serial toxicology tests are unnecessary to guide operative timing of burn patients with amphetamine use.

FRI362 A Rare Case Of Coexisting Pancreatic Neuroendocrine Tumor And Nesidioblastosis

Abstract Disclosure: N. Mon: None. L.K. Tanwani: None. B. Martin: None. C. Scoggins: None. S.L. Mokshagundam: None. Introduction: Nesidioblastosis is a rare cause of endogenous hyperinsulinemic hypoglycemia in adult population. Pancreatic neuroendocrine tumors (NET) are also uncommon among pancreatic tumors. We report a case of a young man who presented with documented Whipple triad and was initially found to have pancreatic cyst. Further evaluation revealed concomitant pancreatic NET and adult nesidioblastosis. Case Report: A 36-year-old Caucasian male with history of anxiety, bipolar, and seizure disorder presented with witnessed seizures and was found to have blood glucose (BG) &amp;lt; 20 mg/dl. He reported recurrent hypoglycemia for 3 years with recent 4-5 ER visits for hypoglycemic seizures. Only medications he was taking were keppra and clonazepam. Physical exam was unremarkable. He was evaluated in Endocrine Clinic and a 72 Hour fast was performed. During the 72 hours fast his BG dropped to 48 mg/dl after 12 hrs. Insulin 16.1 uIU/mL, C peptide 3.02 ng/mL, Proinsulin 60.1 pmol/L, beta-hydroxybutyrate 0.08 mmol/l. BG increased to 116 mg/dl in 30 minutes after 1 mg glucagon injection. Other labs results were: 3PM cortisol 6.6 (7.0-25.0ug/dl), albumin 4.4 mg/dl, HbA1c 5.2%, Alcohol &amp;lt; 5ng/dl, negative urine toxicology screen. CT abdomen without contrast showed a 1.3 cm cyst in the tail of pancreas. Endoscopic ultrasonography revealed a round mixed solid and cystic mass (18x17 mm) with well-defined borders identified in the pancreas tail. The remainder of the pancreas was unremarkable. FNA of the cyst reported findings consistent with a well-differentiated neuroendocrine tumor. He underwent robotic enucleation of distal pancreatic lesion. Postoperative period was uneventful until 2 weeks after procedure when he again started having neuroglycopenic symptoms with lowest BG of 50 mg/dl in the fasting state. He was initiated on diazoxide 50 mg 3 times daily and then 100mg 3 times daily. He continued to have hypoglycemic episodes. Prednisone 10 mg was added at bedtime while waiting for surgery. He underwent distal 80 % pancreatectomy and splenectomy. Hypoglycemia resolved after the surgery. The final pathology was a well-differentiated NET WHO grade I with background neuroendocrine cell hyperplasia/nesidioblastosis. Conclusion: Endogenous hyperinsulinemic hypoglycemia is a rare disorder with nesidioblastosis being the important cause in children and insulinoma in adults, representing a spectrum of pathologic beta cell proliferation. There are very few reports of coexistence of both conditions in adults. Our patient also had an unusual type of insulinoma as it was cystic. The simultaneous occurrence of the two lesions offers significant challenges in diagnosis and management. The mainstay of treatment is surgical resection of insulinoma with localization of insulin hypersecretion; however, how much to remove in nesidioblastosis is still unclear. Presentation: Friday, June 16, 2023

FRI646 Dulaglutide-induced Acute Liver Injury - A Case Report

Abstract Disclosure: M. Shahid: None. A. Hamza: None. D. Vather-Wu: None. S. Sultan: None. P. Nabizadeh: None. Introduction: Drug-induced liver injury (DILI) accounts for almost 10% of all cases of acute hepatitis and can occur within days to months of initiation of a medication. Outcomes can vary from spontaneous resolution on discontinuation of the offending agent to fulminant hepatic failure requiring transplant or even death. Dulaglutide is a GLP-1 receptor agonist that augments glucose-dependent insulin secretion and slows gastric emptying. It is a weekly injectable medication for management of type 2 diabetes mellitus (T2DM). Commonly reported side effects include nausea, vomiting, appetite suppression, and diarrhea or constipation. To date, there have been less than five published case reports of Dulaglutide-induced acute liver injury (ALI). Hereby, we present a case of Dulaglutide-induced ALI with coagulopathy that resolved with the use of N-acetylcysteine (NAC), steroids, and cessation of the medication. Clinical Case: A 38-year-old female with past medical history of T2DM, hypertension, dyslipidemia, and hypothyroidism presented with complaints of nausea, vomiting and epigastric discomfort for 5 days. She reported having malaise and lethargy for a month since she was started on Dulaglutide for management of her T2DM. Her physical examination was unremarkable. The laboratory workup showed AST &amp;gt;6000 U/L, ALT &amp;gt;3300 U/L, ALP 231 U/L, total bilirubin 3.3 mg/dL, direct bilirubin 2.3 mg/dL, indirect bilirubin 1.0 mg/dL, PT 40.3 seconds, INR 3.36 and negative toxicology screening. She was started empirically on intravenous NAC and methylprednisolone, and was followed by serial biochemical measurements. Further workup revealed no evidence of acute viral hepatitis, autoimmune hepatitis, metabolic (alpha-1-antitrypsin deficiency, Wilson disease, hemochromatosis) or alcohol-related ALI. There were no clinical or imaging findings suggestive of ischemic hepatopathy, venous outflow obstruction or biliary obstruction. After ruling out other causes, the ALI was attributed to Dulaglutide use. AST and ALT improved significantly within 7 days and subsequently normalized within 3-4 weeks. Hepatic synthetic function also normalized within 2 weeks without any sequelae. Conclusion: This report highlights the need for awareness regarding potential but not insignificant risk of dulaglutide as cause of DILI. Extensive testing for other causes of ALI was negative and Dulaglutide-induced ALI was the most likely etiology in our case. Given limited data on hepatotoxicity induced by GLP-1 receptor agonists, further research is needed to ascertain this potentially fatal adverse reaction. We hope to contribute to the current medical literature. Presentation: Friday, June 16, 2023

Student Competition (Knowledge Generation) ID 1984525

Background Drug-induced myelopathy has been reported widely for heroin use, but less frequently for amphetamines or fentanyl. Hyperglycemia-induced acute myelopathy has not previously been described. Methods We present a case of toxic/metabolic myelopathy secondary to the aforementioned results in a patient presenting for tertiary inpatient rehabilitation. Results A 28-year-old man with Type 1 Diabetes without complications and polysubstance use (fentanyl and crystal methamphetamine) presented to hospital with quadriparesis and anesthesia. Patient reported he fell down a flight of stairs while using substances and remained on the ground for hours-days as he was acutely paralyzed when he awoke. Initial examination demonstrated a C5 motor level. Pan-CT demonstrated no intracranial or spinous abnormalities. MRI with gadolinium showed cord edema from C1-T4 and patchy enhancement from C4-C7 without cord compression. Diffusion restriction and hemorrhagic transformation were later seen in C4-C7. Initial blood glucose was 66 with no serum ketones. Serum toxicology was negative and urine toxicology was positive for amphetamines and fentanyl. Autoimmune and infectious workups were negative. He received 5 days of pulse steroids and 7 sessions of plasmapheresis with minimal functional or neurological improvement. He was admitted to rehabilitation as a C5 AIS-B and did not exhibit further improvement in motor or sensory function over 3 months of active inpatient rehab. Conclusions Given the pattern of cord enhancement with hemorrhagic transformation, this injury most likely represents acute myelitis induced by hyperglycemia and amphetamines/fentanyl. To our knowledge, this is the first case report where hyperglycemia may have contributed to acute myelopathy.

Prevalence of illicit drug use in young patients with sudden cardiac death

Illicit drug use may accelerate coronary disease and cardiac hypertrophy or stimulate arrhythmias. Rates of illicit drug use in young patients with sudden cardiac death (SCD) are uncertain. The purpose of this study was to identify rates of illicit drug use in young patients with SCD. A prospective statewide registry identified out-of-hospital patients with cardiac arrest aged 18-50 years from April 2019 to April 2021. Clinical characteristics were compared between patients with and without illicit drug use (defined by toxicological results or reported regular use). Illicit drugs included amphetamine-type substances, cocaine, heroin, cannabis, and other drugs. A total of 554(40.2%) of 1378 patients had confirmed cardiac cause of out-of-hospital cardiac arrest, with 523 undergoing toxicological assessment. There were 170 patients (32.5%) having either positive toxicology for illicit drugs (n = 138) or negative toxicology but reported regular drug use (n = 32). Patients with SCD and illicit drug use were more commonly male (81.2% vs 72.3%; P = .028), smokers (38.8% vs 19.8%; P ≤ .0001), and excess alcohol drinkers (30.6% vs 20.6%; P = .012) and had a psychiatric diagnosis (38.8% vs 25.7%; P = .002), lower body mass index (29.4 kg/m2 vs 31.7 kg/m2; P = .0063), and lower rates of hypertension (10.6% vs 18.6%; P = .019). Death commonly occurred while sedentary (47.5%) or during sleep (45.8%). Accounting for these baseline differences, there were no differences in rates of coronary disease or cardiomyopathy. Cannabis (n = 106) was the most common illicit drug identified and polysubstance abuse occurred frequently (n = 25). Approximately one-third of young patients with SCD have positive toxicology at the time of death or reported frequent use of illicit drugs, with high rates of polysubstance abuse.

Secondary Analysis of Agreement Between Negative Timeline Follow Back Report and Negative Urine Toxicology in a Large Trial of Individuals with Opioid Use Disorder.

Timeline follow-back (TLFB) is a self-report measure commonly used as a method of assessing historical drug use in both clinical and research settings. Our study considered rates of agreement between TLFB and an objective biological assay of opioid use. We calculated the rates of agreement between negative report of opioid use for the most recent 8 days on TLFB and urine toxicology (UTOX) results in a large multisite opioid use disorder treatment trial. In total, 3986 assessments were provided by trial participants with both UTOX and TLFB during weeks 1 to 12, 2716 during weeks 13 to 24, and 325 at week 28. Rates of disagreement between negative TLFB and positive opioid UTOX were 2.33% of all assessments (21.68% of those with positive UTOX) over weeks 1 to 12, 2.06% of all assessment (25.00% of those with positive UTOX) over weeks 13 to 24, and 9.85% of all assessments (26.02% of those with positive UTOX) at week 28. Negative TLFB seems to be generally associated with negative results on urine toxicology.

69 Methamphetamine Positivity Prior to Burn Surgery Does not Adversely Affect Intraoperative or Inpatient Outcomes

Abstract Introduction The treatment of burn patients using amphetamines is challenging for hemodynamic and behavioral reasons. In addition, recent amphetamine use may also pose intraoperative risks. Due to insufficient literature to guide the safety and timing of operative care, wide practice variation exists in the operative timing for this patient population. We hypothesize that burn excision without negative amphetamine toxicology is safe. Methods We queried the operative and electronic health records of amphetamine-positive patients treated from 2017-2022 at two ABA verified burn centers. The practice guideline at Center A obtains admission toxicology only and proceeds with surgery based on hemodynamic status and operative urgency, whereas Center B sends daily toxicology until a negative test results. The primary safety outcome was the use of vasoactive agents during the index operation. This risk was modeled via logistic regression and adjusted for injury severity and hospital day for index operation. Secondary outcomes included death and inpatient complications. Results A total of 270 patients were identified during the study period. Mean age was 45.5 years (SD 12.9 years), median TBSA was 9.2% and the majority were male (76.7%). There were no significant differences in injury size, age, or male/female proportion between the two sites. Whereas Center A only tested once on admission, Center B obtained a median of 4 toxicology screens prior to surgery. There were no difference in mean induction systolic blood pressure between the 2 sites, although Center A had more patients who had SBP&amp;lt; 95 or &amp;gt;160mmHg on induction (one-way ANOVA p=0.596). The adjusted OR of requiring vasoactive support during surgery was not associated with negative toxicology status (p=0.821). A larger injury size (%TBSA &amp;gt;20) conferred a significant higher risk of vasoactive support (adj. OR 13.42 [3.90 – 46.23], p&amp;lt; 0.001). Clinical outcomes at the 2 sites were similar in the terms of mortality, number of operations, stroke, and hospital length of stay. Conclusions Comparison between 2 ABA verified burn centers identifies a significant variation in practice with regards to serial amphetamine screenings prior to burn surgery. This study indicates that negative toxicology does not impact intraoperative anesthesia management nor subsequent burn clinical outcomes. Applicability of Research to Practice Serial toxicology tests are unnecessary to guide operative timing of burn patients with amphetamine use.

Abstract #1404823: Too Much of a Good Thing: A Case of Levothyroxine Overdose

Levothyroxine is the most prescribed medication in the last decade in the United States and used commonly for treatment of hypothyroidism. Despite this, overdoses with levothyroxine are rare. Patient presentations can range from asymptomatic with a benign course to severe thyrotoxicosis. Here we present a case of an elderly woman with depression and prior suicide attempts who ingested an estimated 3000 mcg of levothyroxine in a suicide attempt. An 86-year-old female with history of hypothyroidism, major depression, bipolar disorder, mild cognitive impairment, multiple prior suicide attempts presented to the hospital 3 hours after intentional ingestion of 3000 mcg of levothyroxine. She denied co-ingestion of other medications. On physical examination, she had blood pressure of 139/76 mmHg, heart rate of 67 beats per minute (bpm), temperature 98.6 °C, respiratory rate 18 breaths/min, and oxygen saturation of 100% on room air. She denied palpitations, shortness of breath, light-headedness, or chest pain. Her neck was supple without a palpable goiter or nodules. She did not have a tremor. She was alert and oriented to time, place. She endorsed feeling depressed and hopeless which had led to the attempted suicide but now felt remorseful for the attempt. Laboratory workup was notable for lithium level 0.24 mEq/L (0.50 – 1.20 mEq/L), potassium 3.3 mEq/L (3.6 – 5.1 mEq/L), and a negative urine toxicology screen. Electrocardiogram showed normal sinus rhythm without evidence of T-wave abnormalities. Thyroid function tests revealed a thyroid stimulating hormone (TSH) of 1.087 μIU/mL (0.350 – 5.500 uIU/mL), total T3 of 360 ng/dL (80 – 180 ng/dL), and free T4 of 11.76 ng/dL (0.8 – 1.80 ng/dL). She was admitted with suicide precautions and initially treated with lorazepam as needed for anxiety. She developed tachycardia of 101 bpm on day 3 and atenolol 25 mg daily was started. Her heart rate remained in the 80 – 100 bpm range until discharge. Her free T4 trended down into the normal range on day 15 of admission and levothyroxine 50 mcg daily was restarted. She was transferred to the inpatient psychiatric unit for further management of her depression. Prior reports have described a benign course after overdose however symptoms may present in a small subset of patients. These symptoms can be mild (tremors, tachycardia, restlessness, headaches, vomiting) or severe (transient hemiparesis, coma). More severe symptoms have been described with higher doses ingested (levothyroxine 75000- 125000 mcg). Therefore, obtaining history and collateral information about the total dose ingested is important. Free thyroxine levels are trended for biochemical follow up and commonly return to normal after two weeks. TSH levels may remain suppressed well beyond the two-week period and therefore are of limited use in an acute setting. Treatment options include close clinical follow up with symptomatic treatment for tachycardia with beta-blockers. Development of severe symptoms may require levothyroxine extraction through hemodialysis or plasmapheresis.

Illicit drug and alcohol use and measures of musculoskeletal function and mental health in orthopaedic trauma patients.

The objective of this study was to describe the relationship between positive toxicology screens and measures of preinjury mental health and physical function in an orthopaedic trauma population. This was a cross-sectional study. Urban Level 1 trauma center. A total of 125 trauma patients gave written consent for this study. Questionnaires such as, Patient Health Questionnaire-9, General Anxiety Disorder-7, PCL-5, and Short Musculoskeletal Function Assessment, were used to survey patients after surgical intervention. Patient Health Questionnaire-9 (P = 0.05) and PCL-5 (P = 0.04) were not found to have significant differences between positive and negative toxicology screens. Both General Anxiety Disorder-7 (P = 0.004) and Short Musculoskeletal Function Assessment function (P = 0.006) were significantly higher in patients with positive toxicology screens. Positive toxicology seems to be associated with preinjury anxiety. Patient reported preinjury function was not adversely affected by the presence of illicit substances or alcohol, nor were levels of post-traumatic stress disorder and depression found to be higher in patients with positive toxicology screens. Level IV Cross-Sectional Study.

Chemsex, HIV, and Psychiatric Diagnosis in Gay or Bisexual Men in Hong Kong

Background: Psychotropic substance use, for chemsex in particular, is common in gay or bisexual men (GBM) with HIV infection. This case-control study examined the association between Axis I psychiatric disorders and active psychotropic substance use, and identified factors affecting the prevalence of psychiatric disorders in HIV-infected GBM. Methods: Participants were 62 HIV-infected self-identified GBM who reported psychotropic substance use in the past 1 year (cases), and 55 HIV-infected self-identified GBM without psychotropic substance use in the past 1 year and had negative toxicology tests at recruitment (controls). The Chinese-bilingual Structured Clinical Interview for DSM-IV (Axis I, Patient version) was followed to establish the psychiatric diagnoses. Socio-demographic data, level of social support, HIV-related data, and pattern of psychotropic substance use were collected. Results: Cases had lower level of social support, more depressive disorders (AOR 3.4, 95% CI 1.3-8.7, p=0.01) and psychotic disorders (AOR 7.2, 95% CI 1.2-41, p=0.03) but not anxiety disorders. Significant difference in the prevalence of psychiatric disorders was only evident for disorders with onset after HIV diagnosis. Methamphetamine dependence, weekly methamphetamine use for 2 years or more, using methamphetamine beyond chemsex, duration of HIV diagnosis were significant predictors for psychiatric disorders in the cases. Conclusion: Active psychotropic substance use in HIV-infected gay or bisexual men was associated with an overall 3-fold increase in Axis I psychiatric disorders. Coordinated efforts from HIV, psychiatric and substance use services are needed to prevent harms arising from chemsex and to identify those in need and facilitate treatment access.

The role of the bicuspid aortic valve in sudden cardiac death–findings at cardiac autopsy

BackgroundBicuspid aortic valve (BAV) is the most common congenital cardiac defect in the adult population, with a prevalence of 0.5%-2%. It is well recognized that aortic stenosis (AS), aortic regurgitation (AR) and aertopathy may develop by the fifth or sixth decade of life. There is a paucity of autopsy studies evaluating the hearts of subjects with BAV. The aim of this study is to ascertain the role of BAV in cases of sudden cardiac death. MethodsA database of 6325 whole hearts referred to a specialist cardiac pathology center between 2004 and 2021 was reviewed to identify a subgroup of 91 subjects with a BAV reported. All cases had a negative full body autopsy and toxicology before being referred and subsequently underwent detailed cardiac evaluation including histological analysis by expert cardiac pathologists. ResultsThe mean age of death was 37 ± 16 years (84% male). Death was attributed to aortic valve or aortic disease in 57% (n = 52) of cases; AS 30% (n = 27), endocarditis 11% (n = 10), aortic dissection (AD) 9% (n = 8) and AR 8% (n = 7). In the remaining 43% of cases, BAV was an incidental finding. ConclusionThe majority of deaths in young individuals with BAV were attributed to complications related to the aortic valve or aorta indicating that BAV is not a benign condition. When a BAV is identified, individuals should be appropriately follow-up with imaging to inform the optimal timing of intervention before a complication develops that may predispose the individual to a premature death.

Increased lung weight in fatal intoxications is not unique to opioid drugs.

Fatal intoxications with opioids are known to be associated with an increased lung weight, as well as with brain and pulmonary edema and urinary retention. However, there is evidence to suggest that fatal intoxications with non-opioid substances are also associated with increased lung weight; however, the latter aspect has not been comprehensively analyzed. To determine to what extent opioid and non-opioid substances are associated with increased lung and brain weight, we studied these organs in cases where the cause of death was attributed to intoxication with a single agent. Using data from cases autopsied at the National Board of Forensic Medicine (NBFM) in Sweden from 2009 through 2019 where the cause of death was attributed to a single substance, we created models of combined lung weight and brain weight. The models used age and sex as predictors as well as nested varying effects for the specific intoxicant and category of intoxicant. Suicidal hanging with negative toxicology cases served as controls. The population majority was male among both intoxications (68%) and controls (83%). The most common single substance group was opioids. All tested substances were associated with heavier lungs than controls, with the largest effect in the opioid group. Our findings show that several substances are associated with increased lung weight and that among intoxication deaths there is no difference in expected brain weight between substances. Hence, heavy lungs, without a reasonable explanation, should prompt a broad toxicological screening.

Next-generation sequencing of postmortem molecular markers to support for medicolegal autopsy

In most cases, sudden unexplained death (SUD) is caused by hereditary cardiac arrhythmias that standard forensic autopsy procedures cannot prove. For this reason, forensics analysis must apply other methodologies to uncover related factors. For example, postmortem molecular analysis (molecular autopsy) based on next-generation sequencing represents a promising and effective tool for diagnosing SUD. This analysis allows scientists to detect well-known, new, and rare pathogenic exonic variants or those with unknown significance that could be related to the cause of sudden death. Using exome sequencing, we identified rare exon variants in MYBPC3, KCND3, TTN, and ANK3 in a fifteen-year-old male SUD case with negative toxicology analysis and autopsy showing microscopic abnormality of heart fiber disarray. Our findings suggested that this case might be associated with cardiac channelopathy long QT syndrome, type 2, as a potential causative factor.

Pre-injury stimulant use in isolated severe traumatic brain injury: effect on outcomes

PurposeThe aim of this study was to assess the impact of pre-injury stimulant use (amphetamine, cocaine, methamphetamine and/or ecstasy) on outcomes after isolated severe traumatic brain injury (TBI).MethodsRetrospective 2017 TQIP study, including adult trauma patients (≥16 years old) who underwent drug and alcohol screening on admission and sustained an isolated severe TBI (head AIS ≥3). Patients with significant extracranial trauma (AIS ≥3) were excluded. Epidemiological and clinical characteristics, procedures and outcome variables were collected. Patients with isolated stimulant use were matched 1:1 for age, gender, mechanism of injury, head AIS and overall comorbidities, with patients with negative toxicology and alcohol screen. Outcomes in the two groups were compared with univariable and multivariable regression analysis.Results681 patients with isolated TBI and stimulant use were matched with 681 patients with negative toxicology and alcohol screen. The incidence of hypotension and CGS <9 was similar in the two groups.In multivariable regression analysis, stimulant use was not independently associated with mortality (OR 0.95, 95% CI 0.61–1.49). However, stimulant use was associated with longer hospital length of stay (HLOS) (RC 1.13, 95%CI 1.03–1.24).ConclusionPre-injury stimulant use is common in patients admitted for severe TBI, but was not independently associated with mortality when compared to patients with negative toxicology. However, stimulant use was associated with a significant longer HLOS.