Yong Sung Cha

Immune mediators are elevated due to carbon monoxide (CO) poisoning but their role in the development of neurological deficits is unknown. Circulating microparticles (MPs) are elevated in response to CO and correlate with the development of neurological complications. We hypothesized that interleukin (IL)-1β is carried by MPs and contributes to the development of neurological sequelae (NS). Blood-borne IL-1β in CO-poisoned patients is almost exclusively carried by MPs. Healthy humans have 0.8 ± 0.8 (n = 27) MPs/μL bearing IL-1β on the membrane surface. IL-1β-bearing MPs obtained from patients at the time of CO poisoning diagnosis who recover (Global Deterioration Score [GDS] = 1 at 1 month) numbered 35 ± 12/μL (n = 27, p < 0.001 vs. control) and patients who sustained NS (GDS > 1 at 1 month) had 75 ± 38/μL (n = 27; p < 0.001 vs. control and CO-recovered groups). Twice as many MPs carry IL-1β cargo as express surface-bearing IL-1β. The concentration is higher post-CO but does not correlate with NS. Those with NS have 43.8 ± 42.0 pg IL-1β /10⁶ MPs, and those with GDS = 1 have 33.0 ± 32.0 pg/10⁶ MPs, versus controls 5.4 ± 0.3 pg/10⁶ MPs, p < 0.001. In a murine CO model, MPs IL-1β cargo follows similar proportions to humans. Pharmacologic blockade of IL-1β using an IL-1 receptor antagonist or neutralizing anti-IL-1β antibody inhibited neuroinflammation and preserved neurological function. Results demonstrate that brain-derived MPs liberated via the glymphatic system to the peripheral circulation activate neutrophils which are the prime generators of IL-1β-bearing MPs that maintain a cycle of neuroinflammation. Targeting IL-1β disrupts MP-mediated inflammation.

Background/Objectives: Multiple organ failure is the main cause of mortality in severely injured patients who survive the early post-trauma phase. Myeloperoxidase and delta neutrophil indices may serve useful markers for the early diagnosis of an inflammatory condition. We aimed to ascertain the use of these indices for predicting multiple organ failure after a major trauma. Methods: A retrospective study was performed based on a level I trauma center database that included trauma patients with an injury severity score of >15 points. Organ function was evaluated according to the sequential organ failure assessment score within at least 48 h of admission and the myeloperoxidase and delta neutrophil indices, which were measured every morning. Results: A total of 96 patients were included in this study. Compared with the non-multiple-organ-failure group, the multiple organ failure group had similar myeloperoxidase indices but a significantly higher delta neutrophil index. Multivariate logistic regression analysis revealed no significant difference in the predictive power among the post-trauma multiple organ failure models that included various factors, although model 7, which combined the sequential organ failure assessment score and the myeloperoxidase and delta neutrophil indices, tended to have the maximum predictive power. Conclusions: Early delta neutrophil index (DNI) values and the composite model incorporating SOFA, absolute MPXI, and DNI each demonstrated moderate ability to predict multiple organ failure after major trauma. Prospective multicenter studies that include granular treatment variables are warranted to validate these biomarkers and to explore whether their incorporation into real-time decision tools can improve outcomes.

Background/Objectives: The concept of the “smoker’s paradox” in prior research posits that smoking could potentially offer neuroprotective effects in cases of acute carbon monoxide (CO) poisoning. This study aimed to determine the validity of this hypothesis by minimizing selection bias and confounding variables in a comparison of neurocognitive outcomes between smokers and non-smokers following acute CO poisoning. Methods: A total of 1150 patients were included in this retrospective study. Propensity Score Matching (PSM) was used to control for variables such as age, initial Glasgow Coma Scale (GCS) score, co-morbidities, and HBO₂ therapy application. Neurocognitive outcomes were assessed and compared between smokers and non-smokers. Results: In the initial analysis, 1150 patients were divided into non-smoking (61.7%) and smoking (38.3%) groups. Before PSM, smokers had a lower rate of poor outcomes (12.1% vs. 6.8%, p = 0.004). However, baseline differences emerged, with non-smokers being older with longer CO exposure, while smokers had more males and higher rates of intentional CO poisoning and drug ingestion. Smokers had a 0.56 times lower relative risk of poor outcomes compared to non-smokers (95% CI: 0.38–0.84, p = 0.004). After meticulous 1:1 PSM with 15 covariates, 317 patient pairs were matched, creating balanced cohorts. Neurocognitive outcomes at 1 month post-CO exposure showed no significant differences between matched non-smoking and smoking groups (9.8% vs. 7.9%, p = 0.461). Post-PSM, the relative risk for poor outcomes remained approximately 0.81 times lower in smokers compared to non-smokers, but with no statistical significance [0.81 (95% CI: 0.49–1.33, p = 0.402)]. Conclusions: Our findings do not support the idea of a protective effect from smoking in the context of acute CO poisoning. After accounting for potential confounders through PSM, we found that smoking status was not significantly associated with more favorable neurocognitive outcomes.

The mechanism for neurological deficits from carbon monoxide (CO) poisoning is unclear. In a series of 150 patients with CO poisoning, we found marked elevations of blood-borne inflammatory filamentous (F-) actin–coated microparticles (MPs), neutrophil activation, and a 90% reduction in the normal level of plasma gelsolin (pGSN), a protein capable of lysing F-actin–coated MPs. This led to studies in a murine model where the same events occur and cause neuroinflammation with cognitive dysfunction. All events are recapitulated when F-actin MPs are injected intravenously, which establishes a blood-to-brain-to-blood inflammatory cycle that persists for weeks. All changes, including cognitive dysfunction, can be abrogated by an injection of human recombinant pGSN within 2 weeks after CO poisoning. These findings demonstrate that CO-induced neurological injury has an inflammatory etiology. Because of MP-mediated communications between the brain and systemic circulation, CO-induced cognitive deficits may be reversible with a pharmaceutical intervention.

Background: We aimed to investigate the association between acute carbon monoxide (CO) poisoning and the risk of internal malignancies, including hematologic malignancies. Methods: The study population was derived from the National Health Insurance Service (NHIS) database of Korea between 2002 and 2022. Adults diagnosed with CO poisoning and controls were included. Demographics, socioeconomic statuses, lifestyle factors, and comorbidity profiles of participants were retrieved from the NHIS database. Covariates potentially associated with disease outcomes were selected based on the available literature and biological plausibility, balanced between the two cohorts using inverse probability of treatment weighting, and applied to adjust multivariable models. Results: Overall, 42,874 patients with CO poisoning and 905,285 controls were included; both cohorts comprised 44.3% females. The mean age of the CO poisoning and controls was 51.5 and 50.9 years, respectively. Patients with CO poisoning had a 1.02-fold increase in the overall risk of malignancy (a 1.03-fold increase in solid organ malignancies and a 0.71-fold decrease in hematologic malignancies) compared with controls. The risk of internal malignancy was increased in the oral cavity (adjusted hazard ratio, 1.33; 95% confidence intervals, 1.19–1.49), lungs (1.39; 1.33–1.46), bone (1.68; 1.23–2.30), cervix (1.32; 95% CI, 1.17–1.49), and kidneys (1.14; 1.04–1.24). Conversely, the risk of internal malignancies was decreased in the thorax (0.59; 0.45–0.77), anus (0.14; 0.06–0.34), uterus (0.71; 0.60–0.82), ovaries (0.59; 0.45–0.77), prostate (0.89; 0.84–0.95), Hodgkin lymphoma (0.35; 0.20–0.61), non-Hodgkin lymphoma (0.67; 0.59–0.75), and multiple myeloma (0.36; 0.30–0.43). Conclusions: CO poisoning was associated with the development of internal malignancies.

Objective: Carbon monoxide poisoning can cause migraine-like attacks. However, the association between carbon monoxide poisoning and the risk of migraine has not been thoroughly studied. This study aimed to investigate the long-term risk of migraine in patients with carbon monoxide poisoning.Methods: This nationwide, population-based cohort study was conducted using the administrative database of the National Health Insurance Service of Korea from 2002 to 2021. Patients with carbon monoxide poisoning with at least one visit documented according to the International Classification of Diseases, 10th Revision code T58 were included. Patients were only included if they had the same diagnostic code at two or more outpatient clinic visits. The primary outcome of this study was the incidence of migraine after carbon monoxide poisoning.Results: The overall risk of migraine was higher in the carbon monoxide poisoning group regardless of age, sex, or use of hyperbaric oxygen therapy (adjusted hazard ratio, 1.37; 95% confidence interval, 1.28–1.48). The carbon monoxide poisoning group had a persistently higher cumulative incidence of migraine during the observation period than the control group.Conclusion: Carbon monoxide poisoning was associated with an increased overall risk of developing migraine during long-term follow-up.

Park E, et al. J Korean Med Sci. 2025 Nov;40:e339. https://doi.org/10.3346/jkms.2025.40.e339

Background: Hyperbaric oxygen therapy (HBOT) involves inhaling nearly 100% oxygen in a pressurized environment and is commonly used to treat various diseases and injuries. Despite its well-known safety, HBOT is associated with side effects, with frequent middle ear barotrauma (MEB) and oxygen toxicity. Understanding the characteristics and risk factors associated with these side effects is critical for improving patient compliance and treatment outcomes. Methods: This retrospective multicenter study aimed to analyze the characteristics and factors associated with side effects during HBOT using a computer-controlled pressurized monoplace hyperbaric chamber. We conducted a retrospective observational study across the two tertiary hospitals in Korea, involving patients who received HBOT from October 2016 for one hospital and October 2017 for another hospital to June 2020. Data were extracted from electronic medical records and hyperbaric chamber logs, including patient demographics, medical history, HBOT indications, and details of side effects. Statistical analyses, including chi-square and t-tests, were used to compare variables. Results: A total of 247 patients (mean age: 59.35 ± 15.05 years, 63.56% male) were included. The most common indications for HBOT were sudden sensorineural hearing loss (27.94%) and post-graft/flap (24.29%). Hypertension (46.15%) and diabetes mellitus (39.27%) were the most frequent comorbidities. Otalgia was the most prevalent side effect (33.20%), followed by chest discomfort (2.02%) and headache (1.62%). A significant proportion of patients (11.74%) terminated HBOT due to side effects, with most pauses occurring at pressures between 1.2 and 1.4 ATA (26.67%). Side effects, particularly otalgia, significantly impact patient compliance with HBOT. Conclusions: The incidence of side effects varies by pressure level during treatment, suggesting the need for tailored strategies to minimize side effects. This study highlights the importance of patient monitoring and education to improve the safety and efficacy of HBOT in monoplace chambers.

Introduction: Carbon monoxide poisoning may result in various neurological injuries, including acute symptomatic seizures. We aimed to investigate the long-term risk of epilepsy and status epilepticus in patients with previous carbon monoxide poisoning. Methods: The study population was derived from the National Health Insurance Service database of the Republic of Korea between 1 January 2002 and 31 December 2021. We included adults with at least one documented visit to medical facilities because of carbon monoxide poisoning (International Classification of Diseases, Tenth Revision, code T58). Patients were matched, on the same index date, with controls, without a T58 code, for age, sex, insurance type, income level, and residence location in a 1:1 ratio. Follow-up continued until death, migration, or the end of the observation period (31 December 2021). The primary outcome was the incidence of epilepsy (codes G40 or R56) and status epilepticus (code G41). Results: This study included 53,380 patients with carbon monoxide poisoning and 53,380 controls, with 44.2% women and a mean age of 45.7 years. The mean (+/- SD) follow-up period was 5.7 +/- 4.3 years in the carbon monoxide poisoned group and 6.4 +/- 4.4 years in controls. The overall risk of epilepsy (adjusted hazard ratio 2.60; 95% CI: 2.43-2.78; P < 0.001) and status epilepticus (adjusted hazard ratio 4.10; 95% CI: 2.84-5.92; P < 0.001) was significantly increased in the carbon monoxide poisoned group compared to controls. The risk of epilepsy and status epilepticus was increased in patients with previous carbon monoxide poisoning, regardless of sex, age or a history of stroke, neurodegenerative diseases, or central nervous system tumour or infection. However, in the subgroup analysis according to age, the highest risk of epilepsy and status epilepticus was observed in patients less than 40 years of age. Discussion: In this population-based cohort study, previous carbon monoxide poisoning was associated with an increased risk of epilepsy and status epilepticus. The risk was more noticeable in patients aged less than 40 years. Further studies are needed to confirm such an association in other populations. Conclusions: Previous carbon monoxide poisoning was associated with an increased risk of epilepsy and status epilepticus, particularly in the younger population. The long-term management of survivors of carbon monoxide poisoning should include monitoring for epilepsy and status epilepticus.

Hyperbaric oxygen therapy (HBOT) involves inhaling nearly 100% oxygen in a pressurized environment and is commonly used to treat various diseases and injuries. Despite its well-known safety, HBOT is associated with complications, with frequent middle ear barotrauma (MEB) and oxygen toxicity. Understanding the characteristics and risk factors associated with these complications is critical for improving patient’s compliance and treatment outcomes. This retrospective multicenter study aimed to analyze the characteristics and factors associated with complications during HBOT using a computer-controlled pressurized monoplace hyperbaric chamber. We conducted a retrospective observational study across two tertiary hospitals in Korea, involving patients who received HBOT from October 2017 to June 2020. Data were extracted from electronic medical records and hyperbaric chamber logs, including patient demographics, medical history, HBOT indications, and details of complications. Statistical analyses, including chi-square and t-tests, were used to compare variables. A total of 247 patients (mean age: 59.35 ± 15.05 years, 63.56% male) were included. The most common indications for HBOT were sudden sensorineural hearing loss (27.94%) and post-graft/flap (24.29%). Hypertension (46.15%) and diabetes mellitus (39.27%) were the most frequent comorbidities. Otalgia was the most prevalent side effect (33.20%), followed by chest discomfort (2.02%) and headache (1.62%). A significant proportion of patients (11.74%) terminated HBOT due to complications, with most pauses occurring at pressures between 1.2 to 1.4 ATA (26.67%). Complications, particularly otalgia, significantly impact patient compliance with HBOT. The incidence of complications varies by pressure level during treatment, suggesting the need for tailored strategies to minimize complications. This study highlights the importance of patient monitoring and education to improve the safety and efficacy of HBOT in monoplace chambers.