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OBJECTIVES: Our study aimed to investigate both the independent and combined effects of second-hand smoking (SHS) and alcohol intake on the occurrence of stroke. METHODS: Utilizing the Korean Genome Epidemiology Study (KoGES) prospective cohort data, our primary exposure variables were SHS exposure and alcohol intake. The occurrence of stroke served as the main outcome of interest. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox regression analysis. To assess the synergistic influence of SHS and alcohol intake on stroke incidence, a joint test was conducted. RESULTS: SHS exposure correlated with an HR of 1.53 (95% CI, 1.19-1.98) for stroke risk. The combined exposure to SHS and alcohol yielded an elevated stroke risk with an HR of 1.75 (95% CI, 1.20-2.55). CONCLUSIONS: Our research highlights the combined influence of SHS exposure and alcohol intake on stroke susceptibility.

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BACKGROUND: Previous studies reported that vitamin B-12 deficiency is associated with an increased risk of stroke. However, studies examining the association between excessive vitamin B-12 and stroke risk are limited. Our study aimed to investigate the relationship between excessive vitamin B-12 concentrations and risk of stroke and explore whether this association varies according to sex. METHODS: Utilizing the Korean Genome Epidemiology Study (KoGES) prospective cohort data, our primary exposure variables were vitamin B-12 plasma concentration and sex. The occurrence of stroke served as the main outcome of interest. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox regression analysis. An interaction analysis was conducted to assess the interaction effect of vitamin B-12 and sex on stroke incidence. RESULTS: Cox proportional logistic regression analysis, adjusting for confounders, showed that excessive vitamin B-12 did not significantly alter stroke risk (HR: 1.22, 95% CI: 0.82, 1.71) and revealed no significant sex-based differences in stroke risk (HR: 0.90, 95% CI: 0.75, 1.04). However, interaction analysis indicated that excessive vitamin B-12 was linked to a significant increase in stroke risk in males (HR: 1.81, 95% CI: 1.10, 2.99) but not in females (HR: 1.04, 95% CI: 0.66, 1.60), with statistically significant interaction effect (P < 0.01). CONCLUSIONS: Our study demonstrated that although excessive vitamin B-12 alone does not significantly increase stroke risk, it increases risk in males when considering the interaction with sex.

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BACKGROUND: The impact of snoring and diabetes on stroke risk is unclear. This study examined the association between snoring and stroke risk and how it varies with diabetes mellitus (DM) status. METHODS: This research was conducted as a prospective cohort study. A total of 4,352 subjects were included in the analysis, with a mean follow-up time of 13.7 years. The study used snoring history obtained through interviews as the primary exposure variable and DM as the secondary exposure variable. The main outcome measured was the occurrence of stroke. Cox regression analysis was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Additionally, a joint test was conducted to evaluate the combined effect of snoring and diabetes on the occurrence of stroke. RESULTS: In our study of 4,352 subjects, 1,135 (26.1%) had a history of snoring, 233 (5.4%) had diabetes mellitus, and over the 18-year observation period, there were 168 cases of new-onset stroke. Snoring was not associated with an increased risk of stroke (HR: 0.95, 95% CI [0.68-1.33]), but DM significantly elevated the risk of stroke (3.02 [1.96-4.65]). In the interaction analysis of snoring and DM status on stroke risk, snoring was a significant risk factor for stroke only in the population with DM (2.89 [1.07-7.60]). Compared to non-snoring and non-DM, the multivariate HRs for stroke were 1.09 (0.76-1.57) for snoring and non-DM, 1.64 (0.83-2.82) for non-snoring and DM, and 2.95 (1.42-5.45) for snoring and DM. CONCLUSION: Diabetes mellitus was associated with an increased risk of stroke, while a history of snoring was not. In a sub analysis, snoring appeared to be associated with an increased risk of stroke among subjects with diabetes mellitus.

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OBJECTIVE: Driving under the influence (DUI) of alcohol is a major risk factor for fatal road traffic injuries (RTIs) worldwide. This study aimed to investigate the relationship between the implementation of new acts on DUI of alcohol and the clinical outcomes of patients with severe RTIs in Korea. METHODS: This is a community-based cross-sectional study using a nationwide severe trauma registry in Korea. In 2018, 2 acts with the Yoon Chang-Ho Act (Yoon's Act) were passed to strengthen the punishment for drunk driving fatal RTIs (first Yoon's act) and lower the blood alcohol concentration limit to restrict driver's licenses (second Yoon's act). The first Yoon's act was implemented on December 18, 2018, and the second Yoon's act was implemented on June 25, 2019. The study periods were categorized as pre-Act-1, pre-Act-2, Act-1, and Act-2 according to the application of Yoon's Act, and the study outcome was in-hospital mortality. Multivariable logistic regression analysis was conducted to estimate the relationship of the new acts and in-hospital mortality. RESULTS: Among a total of 20,376 patients with severe RTIs and 7,928 patients (drivers) with RTIs (hereafter drivers), the in-hospital mortality rates were 20.8% and 17.0%, and alcohol-related RTIs accounted for 9.7% and 8.1%, respectively. Severe RTIs tended to increase with each period (25.5 cases/day, 24.5 cases/day, 26.8 cases/day, and 30.4 cases/day, P for trend <.01). In-hospital mortality significantly decreased during the Act-2 period compared to the pre-Act-2 period for all patients with severe RTIs (adjusted odds ratio = 0.54, 95% confidence interval 0.43-0.67) and drivers with RTIs (adjusted odds ratio = 0.50, 95% confidence interval 0.34-0.73). CONCLUSIONS: Implementation of the new acts on DUI of alcohol was associated with lower odds for in-hospital mortality for patients with severe RTIs. Further studies are needed to evaluate the long-term impact of the new acts on reducing alcohol-related RTIs.

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PURPOSE: As people living with cancer increase in the aging society, cancer-related emergency department (ED) visits are also increasing. This study aimed to investigate the epidemiologic characteristics of non-emergent cancer-related ED visits using a nationwide ED database. MATERIALS AND METHODS: A cross-sectional study was conducted using the National Emergency Department Information System (NEDIS) database. All cancer-related ED visits between 2016 and 2020 were included. The study outcome was non-emergent ED visits, defined as patients triaged into non-emergent condition at both the time of arrival at ED and discharge from ED and were discharged without hospitalization. RESULTS: Among 1185871 cancer-related ED visits over 5 years, 19.0% (n=225491) were classified as non-emergent visits. While abdominal pain and fever are the top chief complaints in both emergent and non-emergent visits, non-emergent visits had high proportions of abdomen distension (4.8%), ascite (2.4%), and pain in lower limb (2.0%) compared with emergent visits. The cancer types with a high proportion of non-emergent visits were thyroid (32.4%) and prostate cancer (30.4%). Adults compared with children or older adults, female, medical aid insurance, urban/rural ED, direct-in compared with transfer-in, and weekend visit were associated with high odds for non-emergent visits. CONCLUSION: Approximately 20% of cancer-related ED visits may be potentially non-emergent. A significant number of non-emergent patients visited the ED due to cancer-related symptoms. To improve the quality of care for people living with cancer, the expansion of supportive care resources besides of ED, including active symptom control, is necessary.

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STUDY OBJECTIVES: Considering the increased prevalence and more severe manifestations of insomnia among females along with established sex differences in ischemic stroke (IS) occurrence, this research aimed to examine the potential effects of the interaction between insomnia and sex on the incidence and outcome of IS. METHODS: We used data from the Korean Genome and Epidemiology Study (KoGES). The main exposure variables were insomnia history and sex. The main outcome was the occurrence of IS observed in biennial follow-up surveys. Cox proportional regression analysis was performed to estimate the effects of insomnia and sex on IS incidence. We also conducted interaction analysis to investigate the interaction effects between insomnia and sex on IS incidence. RESULTS: During 19 years of follow-up involving 8,933 individuals, we documented 370 cases of new-onset stroke (2.88 cases per 1,000 person-years). Cox proportional regression analysis showed that insomnia and female sex did not increase the risk of IS (HR: 1.13 [95% CI: 0.86-1.51] and HR: 0.86 [95% CI: 0.63-1.17], respectively). Interaction analysis demonstrated that stroke risk was increased only among females with insomnia (HR: 1.34 [95%: 1.05-1.80]) compared with those without insomnia. CONCLUSIONS: Our study highlights the significance of considering sex-specific factors when evaluating the relationship between insomnia and IS risk, particularly emphasizing the unique role of insomnia in IS risk among females.

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OBJECTIVES: Our study aimed to investigate the association between shift work and stroke and determine whether this association varies depending on the presence of insomnia. METHODS: Utilizing the KoGES prospective cohort data, our primary exposure variables were shift work and insomnia. The occurrence of stroke was the main outcome of interest. Hazards ratios and 95% confidence intervals were estimated using Cox regression analysis. An interaction analysis was conducted to assess the interaction of shift work and insomnia on stroke incidence. RESULTS: In the interaction analysis, shift work was significantly associated with stroke incidence only in groups with insomnia and a hazards ratio of 2.49 (95% confidence interval, 1.02-6.11). CONCLUSIONS: Our study demonstrated that shift work was associated with a higher risk of stroke among the population with insomnia.

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OBJECTIVE: Our study hypothesizes that the interaction between depression, alcohol intake, and smoking status can significantly influence the risk of acute coronary syndrome (ACS). We aim to investigate the magnitude of the association between depression and ACS risk and explore how alcohol intake and smoking status affect this association. METHODS: We used data from the Korean Genome and Epidemiology Study. The primary exposure of interest was the presence of depression, as measured using the Beck Depression Inventory score at baseline. The primary outcome was the occurrence of ACS observed in the biennial follow-up surveys. We used Cox proportional regression analysis to estimate the effect of depression on ACS incidence. We conducted interaction and joint effect analyses to explore the interactions between depression and health-related habits including alcohol intake and smoking with regard to ACS incidence. RESULTS: During 16 years of follow-up among 3,254 individuals, we documented 88 cases of new-onset ACS (2.2 cases per 1,000 personyears). We found no association between depression and ACS risk; furthermore, the effect of depression on ACS risk by alcohol intake and smoking status did not differ significantly. In the analysis to observe the joint effect of smoking and depression, the multivariate hazard ratios of ACS were 1.26 (95% confidence interval [CI], 0.67-2.36) for non-smoking and depression, 1.52 (95% CI, 0.83-2.82) for smoking and non-depression, and 2.79 (95% CI, 1.21-6.41) for smoking and depression compared with non-smoking and non-depression. CONCLUSION: Our study reveals the combined effect of depression and smoking on ACS risk, highlighting the potential benefits of concurrent interventions for both depression and smoking for cardiovascular health.

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Genetic, environment, and behaviour factors have a role in causing sudden cardiac arrest (SCA). We aimed to determine the strength of the association between various risk factors and SCA incidence. We conducted a multicentre case-control study at 17 hospitals in Korea from September 2017 to December 2020. The cases included out-of-hospital cardiac arrest aged 19-79 years with presumed cardiac aetiology. Community-based controls were recruited at a 1:1 ratio after matching for age, sex, and urban residence level. Multivariable conditional logistic regression analysis was conducted. Among the 1016 cases and 1731 controls, 948 cases and 948 controls were analysed. A parental history of SCA, low educational level, own heart disease, current smoking, and non-regular exercise were associated with SCA incidence (Adjusted odds ratio [95% confidence interval]: 2.51 [1.48-4.28] for parental history of SCA, 1.37 [1.38-2.25] for low edication level, 3.77 [2.38-5.90] for non-coronary artery heart disease, 4.47 [2.84-7.03] for coronary artery disease, 1.39 [1.08-1.79] for current smoking, and 4.06 [3.29-5.02] for non-regular exercise). Various risk factors related to genetics, environment, and behaviour were independently associated with the incidence of SCA. Establishing individualised SCA prevention strategies in addition to general prevention strategies is warranted.

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There are controversies about the effects of alcohol intake shortly before injury on prognosis of traumatic brain injury (TBI) patients. We investigated the association between alcohol intake and functional/survival outcomes in TBI patients, and whether this effect varied according to age and sex. This was a prospective international multicenter cohort study using the Pan-Asian trauma outcomes study registry in Asian-Pacific countries, conducted on adult patients with TBI who visited participating hospitals. The main exposure variable was alcohol intake before injury, and the main outcomes were poor functional recovery (modified Rankin Scale score, 4-6) and in-hospital mortality. Multivariable logistic regression analyses were conducted to estimate the effects of alcohol intake on study outcomes. Interaction analysis between alcohol intake and age/sex were also performed. Among the study population of 12,451, 3263 (26.2%) patients consumed alcohol before injury. In multivariable logistic regression analysis, alcohol intake was associated with lower odds for poor functional recovery [4.4% vs 6.6%, a odds ratio (95% confidence interval): 0.68 (0.56-0.83)] and in-hospital mortality (1.9% vs 3.1%, 0.64 [0.48-0.86]). The alcohol intake had interaction effects with sex for poor functional recovery: 0.59 (0.45-0.75) for male and 0.94 (0.60-1.49) for female (P for-interaction < .01), whereas there were no interaction between alcohol intake and age. In TBI patients, alcohol intake before injury was associated with lower odds of poor functional recovery and in-hospital mortality, and these effects were maintained in the male group in the interaction analyses.

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BACKGROUND: We conducted a comprehensive meta-analysis of prospective cohort studies to analyze the effect of circulating vitamin D level on the risk of sudden cardiac death (SCD) and cardiovascular disease (CVD) mortality. METHODS: Prospective cohort studies evaluating the association between circulating vitamin D and risk of SCD and CVD mortality were systematically searched in the PubMed and Embase. Extracted data were analyzed using a random effects model and results were expressed in terms of hazard ratio (HR) and 95% confidence interval (CI). Restricted cubic spline analysis was used to estimate the dose-response relationships. RESULTS: Of the 1,321 records identified using the search strategy, a total of 19 cohort studies were included in the final meta-analysis. The pooled estimate of HR (95% CI) for low vs. high circulating vitamin D level was 1.75 (1.49-2.06) with I² value of 30.4%. In subgroup analysis, strong effects of circulating vitamin D were observed in healthy general population (pooled HR, 1.84; 95% CI, 1.43-2.38) and the clinical endpoint of SCD (pooled HRs, 2.68; 95% CI, 1.48-4.83). The dose-response analysis at the reference level of < 50 nmol/L showed a significant negative association between circulating vitamin D and risk of SCD and CVD mortality. CONCLUSION: Our meta-analysis of prospective cohort studies showed that lower circulating vitamin D level significantly increased the risk of SCD and CVD mortality.

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BACKGROUND: Insomnia and depression have been known to be risk factors of several diseases, including coronary heart disease. We hypothesized that insomnia affects the out-of-hospital cardiac arrest (OHCA) incidence, and these effects may vary depending on whether it is accompanied by depression. This study aimed to determine the association between insomnia and OHCA incidence and whether the effect of insomnia is influenced by depression. METHODS: This prospective multicenter case-control study was performed using Phase II Cardiac Arrest Pursuit Trial with Unique Registration and Epidemiology Surveillance (CAPTURES-II) project database for OHCA cases and community-based controls in Korea. The main exposure was history of insomnia. We conducted conditional logistic regression analysis to estimate the effect of insomnia on the risk of OHCA incidence and performed interaction analysis between insomnia and depression. Finally, subgroup analysis was conducted in the patients with insomnia. RESULTS: Insomnia was not associated with increased OHCA risk (0.95 [0.64-1.40]). In the interaction analysis, insomnia interacted with depression on OHCA incidence in the young population. Insomnia was associated with significantly higher odds of OHCA incidence (3.65 [1.29-10.33]) in patients with depression than in those without depression (0.84 [0.59-1.17]). In the subgroup analysis, depression increased OHCA incidence only in patients who were not taking insomnia medication (3.66 [1.15-11.66]). CONCLUSION: Insomnia with depression is a risk factor for OHCA in the young population. This trend was maintained only in the population not consuming insomnia medication. Early and active medical intervention for patients with insomnia may contribute to lowering the risk of OHCA.

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Caffeine is one of the most widely consumed psychoactive drugs in the general population. It has a neuroprotective effect in degenerative neurological disorders; however, the association between caffeine and traumatic brain injury (TBI) outcomes is contradictory. The objective of this study was to evaluate the association between serum caffeine concentration at the time of injury and long-term functional outcomes of patients with TBI visiting the emergency department (ED). This was a prospective multi-center cohort study including adult patients with intracranial injury confirmed by radiological examination, who visited five participating EDs within 72 h after TBI. The main exposure was the serum caffeine level within 4 h after injury, and the study outcome was a favorable functional recovery at 6 months after injury. Multi-variable logistic regression analysis adjusted for potential confounders was performed to calculate adjusted odds ratios (AORs) with 95% confidence intervals (CIs). Among the 334 study participants, caffeine was not detected in 102 patients (30.5 %). In patients with identifiable caffeine level, serum caffeine level was categorized into tercile groups; low (0.01-0.58 µg/mL), intermediate (0.59-1.66 µg/mL), and high (1.67-10.00 µg/mL). The proportions of patients with a 6-month favorable functional recovery were 56.9% in the no-caffeine group, 79.2% in the low-caffeine group, 75.3% in the intermediate-caffeine group, and 66.7% in the high-caffeine group (p = 0.006). In multi-variable logistic regression analysis, the low- and intermediate-caffeine groups were significantly associated with a higher probability of 6-month favorable functional recovery compared with the no-caffeine group [AORs (95% CI): 2.82 (1.32-6.02) and 2.18 (1.06-4.47], respectively. This study showed a significant association between a serum caffeine concentration of 0.01 to 1.66 µg/mL and good functional recovery at 6 months after injury compared with the no-caffeine group of patients with TBI with intracranial injury. These results suggest the possibility of using serum caffeine level as a potential biomarker for TBI outcome prediction and of using caffeine as a therapeutic agent in the clinical care of patients with TBI.

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BACKGROUND: Previous studies have reported that Post-Cardiac arrest (PCA) treatments including targeted temperature management (TTM), coronary reperfusion therapy (CRT), and extracorporeal membrane oxygenation (ECMO) are time-sensitive; however, there are no reports of the clinical outcomes of PCA treatment according to the scene time interval (STI). Our study aimed to investigated the clinical outcomes of PCA treatment according to the STI. METHODS: We used a Korean nationwide OHCA cohort database from January 2017 to December 2020. The inclusion criteria were all adult OHCA patients with a presumed cardiac etiology, bystander-witnessed arrest, and prehospital return of spontaneous circulation (ROSC). The outcomes were survival to discharge and good neurological recovery. The main exposure of interest was PCA treatment. We compared the outcomes using multivariable logistic regression, and interaction terms were included in the final model to assess whether the STI modified the effect of PCA treatment on clinical outcomes of OHCA. RESULTS: TTM and CRT were associated with high survival to discharge and good neurological recovery. In the interaction analysis, ECMO had an interaction effect with the STI on a good CPC among patients with OHCA [short STI (0 to 11 min) (1.16 (0.77-1.75)), middle STI (12 to 15 min) (0.66 (0.41-1.06)), and long STI (16 to 30 min) (0.59 (0.40-0.88)) (p for interaction <0.05)]. CONCLUSION: In adult bystander-witnessed patients with OHCA with prehospital ROSC, an STI of >16 min was a risk factor for poor neurological outcome in those patients who underwent ECMO.

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PURPOSE: There has been no report of sex-specific, pediatric age-adjusted shock index (PASI) for pediatric trauma patients in previous studies. We aimed to determine the association between the PASI and in-hospital mortality of pediatric trauma patients and whether this association differs depending on sex. MATERIALS AND METHODS: This is a prospective, multinational, and multicenter cohort study using the Pan-Asian Trauma Outcome Study (PATOS) registry in the Asia-Pacific region, conducted in pediatric patients who visited the participating hospitals. The main exposure of our study was abnormal (elevated) PASI measured in an emergency department. The main outcome was in-hospital mortality. We performed a multivariable logistic regression analysis to estimate the association between abnormal PASI and study outcomes after adjusting for potential confounders. An interaction analysis between PASI and sex was also conducted. RESULTS: Of 6280 pediatric trauma patients, 10.9% (686) of the patients had abnormal PASI. In multivariable logistic regression analysis, abnormal PASI was significantly associated with increased in-hospital mortality [adjusted odds ratios (aOR), 1.74; 95% confidence interval (CI), 1.13-2.47]. Abnormal PASI had interaction effects with sex for in-hospital mortality (aOR, 1.86; 95% CI, 1.19-2.91 and aOR, 1.38; 95% CI, 0.58-2.99 for male and female, respectively) (p<0.01). CONCLUSION: Abnormal PASI is associated with increased in-hospital mortality in pediatric trauma patients. The prediction power of PASI for in-hospital mortality was maintained only in male patients.

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BACKGROUND: Traumatic brain injury (TBI) is a time-sensitive and life-threatening medical condition. We hypothesized that off-hours, which includes night-time, weekends, and holidays, may influence mortality in TBI. Our study aimed to evaluate if the off-hours effect influences mortality in patients with TBI and whether this effect is dependent on the age group. METHODS: This study included patients who experienced TBI and were admitted to Chonnam National University Hospital (CNUH) between 2017 to 2020. The main exposure was arrival time at the emergency department (ED) (off-hours vs. working hours). The main outcome was mortality at hospital discharge. Multivariable logistic regression analysis was conducted to estimate the effect size of off-hours on mortality compared to that of working hours. We performed an interaction analysis between ED admission time and age group on study outcomes. RESULTS: A total of 2086 patients with TBI with intracranial injury who were transported by EMS were enrolled in our registry. In the multivariable logistic regression analysis, there was no significant difference in mortality (AOR, 95% CI (1.05 [0.54-1.81]) in patients visiting the ED during off-hours. In the interaction analysis, the effect measure of ED admission during off-hours on mortality was significant among younger people (0-17 years: 1.16 [1.03-1.31]), compared to that in other age groups (18-64 years: 1.02 [0.48-2.39] and 65-100 years (0.99 [0.51-2.23])). CONCLUSIONS: In patients under 18 years old, admission during off-hours was associated with higher mortality at hospital discharge compared to admission during working-hours in patients with TBI with intracranial hemorrhage. EDs should be designed such that the same quality of emergency care is provided regardless of admission time.

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Cervical spine immobilization (CSI) has been considered an essential part of first aid management after severe trauma; however, the routine use of CSI for traumatic brain injury (TBI) patients is a matter of debate. The purpose of our study was to analyze the effect of CSI on the clinical outcomes of TBI patients and to analyze whether this effect depends on the prehospital mean arterial pressure (MAP) This was a prospective multi-national, multi-center cohort study using Pan-Asian trauma outcome study registry in Asian-Pacific, conducted on adult trauma patients. The main exposure was the implementation of CSI before hospital arrival. The main outcome was poor functional recovery at hospital discharge measured by the modified rankin scale. We performed multilevel logistic regression analysis to estimated the effect size of CSI for study outcomes. Interaction analysis between CSI and MAP on study outcomes were also conducted. CSI for TBI patients is significantly associated with an increased poor functional outcome (adjusted odd ratio, 95% confidence intervals: 1.23 [1.03 - 1.44]). The association of CSI with poor functional outcomes was maintained only in patients with decreased prehospital MAP (1.38 [1.14 - 1.56]), but not in patients with normal MAP (1.12 [0.93 - 1.24]) (P for interaction < .05). Routine use of CSI for patients with TBI, but without cervical spine injury, is associated with poor functional outcomes, but is significant only when the MAP, measured at the scene, was decreased.

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OBJECTIVE: The role of reverse shock index multiplied Glasgow coma scale (rSIG) in patients post-trauma with traumatic brain injury (TBI) has not yet been defined well. Our study aimed to investigate the predictive performance of rSIG according to age group. METHOD: This is a prospective multi-national and multi-center cohort study using Pan-Asian Trauma Outcome Study registry in Asian-Pacific, conducted on patients post-trauma who visited participating hospitals. The main exposure was low rSIG measured at emergency department. The main outcome was in-hospital mortality. We performed multilevel logistic regression analysis to estimate the association low rSIG and study outcomes. Interaction analysis between rSIG and age group were also conducted. RESULTS: Low rSIG was significantly associated with an increase in in-hospital mortality in patients post-trauma with and without TBI (aOR (95% CI): 1.49 (1.04-2.13) and 1.71 (1.16-2.53), respectively). The ORs for in-hospital mortality differed according to the age group in patients post-trauma with TBI (1.72 (1.44-1.94) for the young group and 1.13 (1.07-1.52) for the old group; p < 0.05). CONCLUSION: Low rSIG is associated with an increase in in-hospital mortality in adult patients post-trauma. However, in patients with TBI, the prediction of mortality is significantly better in younger patient group.

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Since glufosinate irreversibly inhibits glutamine synthetase, leading to intracellular accumulation of ammonia, hyperammonemia is considered one of the main mechanisms of glufosinate ammonium toxicity in humans. However, whether hyperammonemia causes neurotoxicity has not yet been studied. Therefore, the purpose of this study was to determine whether the serum ammonia level is elevated before the development of neurotoxicity. In this retrospective observational study, we analyzed data from consecutive patients diagnosed with acute glufosinate ammonium poisoning. The primary outcome was the development of neurotoxicity following the poisoning. Patients who developed neurotoxicity were characterized by higher initial ammonia levels compared to patients without neurotoxicity (121.0 µg/dL [87.0; 141.0] vs 83.0 µg/dL [65.0; 119.0], p < 0.01). However, there was no increase in ammonia levels over time in both the asymptomatic and neurotoxicity groups when serial serum ammonia levels were examined from emergency department admission to hospital discharge. In addition, there was no statistically significant difference between the peak ammonia levels in the asymptomatic group and the peak ammonia levels before symptom onset in the neurotoxicity group (135.0 µg/dL [109.0; 158.0] vs 144.0 µg/dL [120.0; 189.0], p = 0.15). Following the onset of neurotoxicity, the serum ammonia level increased significantly (125.0 [111.0; 151.0] µg/dL to 148.0 [118.0; 183.0] µg/dL, p < 0.01). In conclusion, hyperammonemia cannot be assumed as the cause of neurotoxicity in glufosinate ammonium poisoning and further research is needed to examine the exact mechanism of GA poisoning.

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