Carbon Monoxide Poisoning: From Microbes to Therapeutics.

Carbon monoxide (CO) poisoning leads to 50,000-100,000 emergency room visits and 1,500-2,000 deaths each year in the United States alone. Even with treatment, survivors often suffer from long-term cardiac and neurocognitive deficits, highlighting a clear unmet medical need for novel therapeutic strategies that reduce morbidity and mortality associated with CO poisoning. This review examines the prevalence and impact of CO poisoning and pathophysiology in humans and highlights recent advances in therapeutic strategies that accelerate CO clearance and mitigate toxicity. We focus on recent developments of high-affinity molecules that take advantage of the uniquely strong interaction between CO and heme to selectively bind and sequester CO in preclinical models. These scavengers, which employ heme-binding scaffolds ranging from organic small molecules to hemoproteins derived from humans and potentially even microorganisms, show promise as field-deployable antidotes that may rapidly accelerate CO clearance and improve outcomes for survivors of acute CO poisoning.

Gray matter atrophy and white matter lesions burden in delayed cognitive decline following carbon monoxide poisoning.

Gray matter (GM) atrophy and white matter (WM) lesions may contribute to cognitive decline in patients with delayed neurological sequelae (DNS) after carbon monoxide (CO) poisoning. However, there is currently a lack of evidence supporting this relationship. This study aimed to investigate the volume of GM, cortical thickness, and burden of WM lesions in 33 DNS patients with dementia, 24 DNS patients with mild cognitive impairment, and 51 healthy controls. Various methods, including voxel-based, deformation-based, surface-based, and atlas-based analyses, were used to examine GM structures. Furthermore, we explored the connection between GM volume changes, WM lesions burden, and cognitive decline. Compared to the healthy controls, both patient groups exhibited widespread GM atrophy in the cerebral cortices (for volume and cortical thickness), subcortical nuclei (for volume), and cerebellum (for volume) (p < .05 corrected for false discovery rate [FDR]). The total volume of GM atrophy in 31 subregions, which included the default mode network (DMN), visual network (VN), and cerebellar network (CN) (p < .05, FDR-corrected), independently contributed to the severity of cognitive impairment (p < .05). Additionally, WM lesions impacted cognitive decline through both direct and indirect effects, with the latter mediated by volume reduction in 16 subregions of cognitive networks (p < .05). These preliminary findings suggested that both GM atrophy and WM lesions were involved in cognitive decline in DNS patients following CO poisoning. Moreover, the reduction in the volume of DMN, VN, and posterior CN nodes mediated the WM lesions-induced cognitive decline.

The Combination of Zhuli Decoction and N-butylphthalide Inhibits Cell Apoptosis Induced by CO Poisoning through the PI3K/AKT/GSK-3ß Signaling Pathway.

Carbon monoxide poisoning (COP) represents a significant global health burden, characterized by its morbidity and high mortality rates. The pathogenesis of COP-induced brain injury is complex, and effective treatment modalities are currently lacking. In this study, we employed network pharmacology to identify therapeutic targets and associated signaling pathways of Zhuli Decoction (ZLD) for COP. Subsequently, we conducted both in vitro and in vivo experiments to validate the therapeutic efficacy of ZLD in combination with N-butylphthalide (NBP) for acute COP-induced injury. Our network pharmacology analysis revealed that the primary components of ZLD exerted therapeutic effects through the modulation of multiple targets and pathways. The in vitro and in vivo experiments demonstrated that the combination of NBP and ZLD effectively inhibited apoptosis and up-regulated the activities of P-PI3K (Tyr458), P-AKT (Ser473), P-GSK-3ß (Ser9), and Bcl-2, thus leading to the protection of neuronal cells and improvement in cognitive function in rats following COP, which was better than the effects observed with NBP or ZLD alone. The rescue experiment further showed that LY294002, a PI3K inhibitor, significantly attenuated the therapeutic efficacy of NBP + ZLD. The neuroprotection effects of NBP and ZLD against COP-induced brain injury are closely linked to the activation of the PI3K/AKT/GSK-3ß signaling pathway.

Hypothyroidism following carbon monoxide poisoning: An epidemiological study supported by animal experiments.

Previous studies have suggested a possible association between carbon monoxide poisoning (COP) and hypothyroidism, but the evidence is limited. Therefore, the aim of this study was to further investigate this relationship. Using data from the Taiwan National Health Research Database, we identified 32,162 COP patients and matched with 96,486 non-COP patients by age and index date for an epidemiological study. The risk of hypothyroidism was compared between the two cohorts until 2018. Independent predictors of hypothyroidism were analyzed using competing risk analysis. An animal study was also conducted to support the findings. COP patients had an increased risk of hypothyroidism compared to non-COP patients in the overall analysis (adjusted hazard ratio [AHR]= 3.88; 95 % confidence interval [CI]: 3.27-4.60) and in stratified analyses by age, sex, and comorbidities. The increase in the overall risk persisted even after more than six years of follow-up (AHR= 4.19; 95 % CI: 3.18-5.53). Independent predictors of hypothyroidism, in addition to COP, included age ≥65 years, female sex, hyperlipidemia, and mental disorder. The animal study showed damages in the hypothalamus, pituitary gland, and thyroid, as well as altered hormone levels 28 days after COP exposure. The epidemiological results showed an increased risk of hypothyroidism in COP patients, which was further supported by the animal study. These findings suggest the need for close monitoring of thyroid function in COP patients, especially in those who are age ≥65 years, female, and have hyperlipidemia or mental disorder.

Prognostic value of systemic immune-inflammation index and monocyte-to-HDL-cholesterol ratio in early cardio-cerebral complications in elderly patients with acute severe carbon monoxide poisoning.

To investigate how effectively systemic immune-inflammation index (SII) and Monocyte-to-HDL-cholesterol ratio (MHR) predict the development of early cardio-cerebral complications in elderly patients who have experienced acute severe carbon monoxide poisoning (ASCMP). A retrospective analysis was conducted on 77 elderly patients with ASCMP admitted to the emergency department of Harrison International Peace Hospital from November 2020 to March 2022. The prevalence of early-onset complications among the 77 individuals was 38.96%. Binary Logistics regression analysis showed that SII and MHR were independent influencing factors of early cardio-cerebral complications in elderly patients with ASCMP. The complication group had a longer length of stay, a greater mortality rate, and a higher incidence of delayed encephalopathy after acute carbon monoxide poisoning (p < .05) than the non-complication group. The area under the curve (AUC) of SII and MHR in predicting early cardio-cerebral complications in elderly patients with ASCMP were 0.724 and 0.796, respectively, with 80.0% and 63.3% sensitivity, and 61.7% and 87.2% specificity. The incidence of early cardio-cerebral complications in elderly patients who had ASCMP is high and the prognosis is poor. SII and MHR can be utilized as independent predictors of early cardio-cerebral complications in elderly patients with ASCMP, allowing doctors to diagnose and treat cardio-cerebral complications earlier and improve prognosis.

Effect and molecular mechanism of Sulforaphane alleviates brain damage caused by acute carbon monoxide poisoning:Network pharmacology analysis, molecular docking, and experimental evidence.

Sulforaphane (SFN) has attracted much attention due to its ability on antioxidant, anti-inflammatory, and anti-apoptotic properties, while its functional targets and underlying mechanism of action on brain injury caused by acute carbon monoxide poisoning (ACOP) have not been fully elucidated. Herein, we used a systematic network pharmacology approach to explore the mechanism of SFN in the treatment of brain damage after ACOP. In this study, the results of network pharmacology demonstrated that there were a total of 81 effective target genes of SFN and 36 drug-disease targets, which were strongly in connection with autophagy-animal signaling pathway, drug metabolism, and transcription disorders in cancer. Upon the further biological function and KEGG signaling pathway enrichment analysis, a large number of them were involved in neuronal death, reactive oxygen metabolic processes and immune functions. Moreover, based on the results of bioinformatics prediction associated with multiple potential targets and pathways, the AMP-activated protein kinase (AMPK) signaling pathway was selected to elucidate the molecular mechanism of SFN in the treatment of brain injury caused by ACOP. The following molecular docking analysis also confirmed that SFN can bind to AMPKα well through chemical bonds. In addition, an animal model of ACOP was established by exposure to carbon monoxide in a hyperbaric oxygen chamber to verify the predicted results of network pharmacology. We found that the mitochondrial ultrastructure of neurons in rats with ACOP was seriously damaged, and apoptotic cells increased significantly. The histopathological changes were obviously alleviated, apoptosis of cortical neurons was inhibited, and the number of Nissl bodies was increased in the SFN group as compared with the ACOP group (p < .05). Besides, the administration of SFN could increase the expressions of phosphorylated P-AMPK and MFN2 proteins and decrease the levels of DRP1, Caspase3, and Casapase9 proteins in the brain tissue of ACOP rats. These findings suggest that network pharmacology is a useful tool for traditional Chinese medicine (TCM) research, SFN can effectively inhibit apoptosis, protect cortical neurons from the toxicity of carbon monoxide through activating the AMPK pathway and may become a potential therapeutic strategy for brain injury after ACOP.

Stroke on ECG: a cerebral T-wave change secondary to acute carbon monoxide poisoning.

In clinical management of carbon monoxide (CO) poisoning, serum cardiac enzyme biomarkers and electrocardiogram (ECG) are both highly recommended emergency check-ups to evaluate myocardial injuries. Medical imaging - including head CT or MRI - are not routine for CO poisoning emergency management. We herein report on a comatose patient who was diagnosed with cerebral infarction secondary to 24 hours previous acute CO poisoning, warned by a typical cerebral-type T waves on ECG in advance, and confirmed by a head MRI. Fortunately, the patient made a full recovery based on a timely treatment with medications and hyperbaric oxygen (HBO2) therapy. We would like to propose that a vital, stable, conscious CO poisoning patient who remains a higher risk for hemorrhagic or ischemic stroke should be closely monitored for potential neurological abnormalities, and a continuous ECG monitoring should be reinforced throughout the treatment. A head MRI or CT is a priority in evaluating the secondary cerebral stroke and should be arranged immediately in the event of an abnormal ECG or if unusual new symptoms are apparent.

Short and long-term outcomes of multidimensional physiotherapy in cases with acute compartment syndrome secondary to carbon monoxide poisoning with prolonged forearm compression.

BACKGROUND: Compartment syndrome following carbon monoxide (CO) poisoning and compression, can have a devastating impact on neuromuscular structures, depending on a time-based dosage. PURPOSE: To investigate multidimensional physiotherapy's short-term and long-term outcomes in identical twin cases who developed compartment syndrome due to CO poisoning and prolonged compression. STUDY DESIGN: Case report. METHODS: This study was conducted with two male cases, a 21-year-old identical twin. The loss of consciousness due to CO poisoning lasted for 15 hours. Case one had compartment syndrome that caused damage to the median and ulnar nerves in the right forearm, while Case two had compartment syndrome that caused damage to the radial nerve in the left forearm. No surgical intervention was performed (Fasciotomy etc). RESULTS: The disability, dexterity, hand health status, sensory-motor function, and edema were evaluated. Initial evaluations showed severe sensory and motor dysfunction, disability, and edema. Treatment included Complex decongestive physiotherapy, electrical stimulation, therapeutic ultrasound, orthotics, and exercises. On the 144th day (discharge day), both cases still exhibited weakness in functional strength and sensory loss compared to the uninjured side. At the ninth month, all parameters except strength were similar to the uninjured side in both cases. By the 53rd month, strength also reached normal values. CONCLUSIONS: Multidimensional physiotherapy effectively manages edema, improves sensory-motor function, and enhances hand function in the short and long term.

The Relationship between Fragmented QRS and Myocardial Injury in Patients with Acute Carbon Monoxide Poisoning.

Background and Objectives: Carbon monoxide (CO) intoxication is one of the most common causes of poisoning-related deaths and complications. Myocardial injury is an important complication of CO poisoning. In our study, we aimed to evaluate the relationship between the presence and prevalence of fragmented QRS (fQRS) and myocardial injury in patients with CO intoxication. Materials and Methods: We retrospectively evaluated patients who presented to the emergency department of our tertiary care center with CO intoxication between January 2020 and December 2023. In our study, we performed subgroup analyses according to the presence of myocardial injury and fQRS. We evaluated the parameters and risk factors associated with myocardial injury. Results: Myocardial injury was detected in 44 patients, and fQRS was detected in 38 patients. In the myocardial injury (+) group, the fQRS rate was 38.6%, and the median number of leads with fQRS was 3 (2-6) and was significantly higher than in the myocardial injury (-) group (p < 0.001). We found that carboxyhemoglobin had a significant positive correlation with troponin (p = 0.001) and pro-B-type natriuretic peptide (proBNP) (p = 0.009). As a result of multivariate analysis, we determined that age, creatinine, proBNP, fQRS, and ≥3 leads with fQRS are independent risk factors for myocardial injury. Conclusions: Myocardial injury in CO intoxication patients is associated with proBNP, the presence of fQRS, and the number of leads with fQRS. Age, creatinine level, proBNP, the presence of fQRS, and ≥3 leads with fQRS are independent risk factors for myocardial injury in patients with CO intoxication.

[Mechanism of Butylphthalide in Treating Delayed Encephalopathy After Carbon Monoxide Poisoning Based on Activation of Microglia].

Objective To explore the mechanism of butylphthalide (NBP) in regulating microglia activation and inflammatory cytokine expression in the hippocampus of the mouse model of delayed encephalopathy after carbon monoxide poisoning (DEACMP). Methods Wild-type C57 adult mice with normal cognitive function were selected,and DEACMP was modeled by static inhalation of carbon monoxide.The mice were randomized into three groups:DEACMP,control,and NBP.The NBP group was administrated with NBP suspension at 6 mg/kg by gavage for 21 days,and the DEACMP and control groups were administrated with the same amount of vegetable oil by gavage.The hippocampal injury was observed by HE staining.The protein level of ionized calcium-binding adapter molecule 1 (IBA1) was determined by Western blotting,and the levels of downstream inflammatory cytokines were measured by ELISA. Results Compared with the control group,the DEACMP and NBP groups showed prolonged escape latency (P=0.001,P=0.029),reduced nerve cells (P=0.001,P=0.035),up-regulated expression of IBA1 (P=0.001,P=0.042),increased mean fluorescence intensity of IBA1 (P=0.001,P=0.021),and elevated levels of tumor necrosis factor-α (TNF-α) (P=0.002,P=0.024),interleukin (IL)-6 (P=0.001,P=0.015),and IL-1ß (P=0.001,P=0.023).Compared with the DEACMP group,the NBP group showed shortened escape latency (P=0.025),increased nerve cells (P=0.039),down-regulated expression of IBA1 (P=0.035),decreased average fluorescence intensity of IBA1 (P=0.031),and lowered levels of TNF-α (P=0.028),IL-6 (P=0.037),and IL-1ß (P=0.034). Conclusion NBP can inhibit the activation of microglia and reduce the expression of inflammatory factors,thereby alleviating cognitive dysfunction and brain tissue damage caused by DEACMP.

[A case of massive intrathecal hematoma of the rectus abdominis secondary to acute severe carbon monoxide poisoning].

Acute carbon monoxide poisoning can cause hypoxic injury to multiple organs. Neurological impairment and cardiac dysfunction are common manifestations of severe poisoning patients, but hemorrhagic complications are rare in clinic. The clinical diagnosis and treatment of a case of massive intrathecal hematoma of the rectus abdominis secondary to acute severe carbon monoxide poisoning was reported. The pathophysiological mechanism and treatment strategy of rectus sheath hematoma secondary to acute severe carbon monoxide poisoning was analyzed, in order to improve the understanding of hemorrhagic complications of carbon monoxide poisoning. This case suggests that for patients with a history of cardiovascular disease and taking anticoagulants, clinicians should be alert for the risk of bleeding when making medical decisions.

A Graph Theory Study of Resting-State Functional MRI Connectivity in Children With Carbon Monoxide Poisoning.

BACKGROUND: The effect of carbon monoxide (CO) poisoning on the topology of brain functional networks is unclear, especially in children whose brains are still developing. PURPOSE: To investigate the topological alterations of the whole-brain functional connectome in children with CO poisoning and characterize its relationship with disease severity. STUDY TYPE: Cross-sectional and prospective study. SUBJECTS: A total of 26 patients with CO poisoning and 26 healthy controls. FIELD STRENGTH/SEQUENCE: A 3.0 T MRI system/echo planar imaging (EPI) and 3D brain volume imaging (BRAVO) sequences. ASSESSMENT: We used the network-based statistics (NBS) method to explore between-group differences in functional connectivity strength and a graph-theoretical-based analytic method to explore the topology of brain networks. STATISTICAL TESTS: Student's t-test, chi-square test, NBS, Pearson correlation coefficient, and false discovery rate correction. The statistical significance threshold was set at P < 0.05. RESULTS: The case group's brain functional network topology was impaired in comparison to the control group (reduced global efficiency and small-worldness, increased characteristic path length). According to node and edge analyses, the case group showed topologically damaged regions in the frontal lobe and basal ganglia, as well as neuronal circuits with weaker connections. Also, there was a significant correlation between the patients' coma time and the degree (r = -0.4564), efficiency (r = -0.4625), and characteristic path length (r = 0.4383) of the nodes in the left orbital inferior frontal gyrus. Carbon monoxide hemoglobin content (COHb) concentration and right rolandic operculum node characteristic path length (r = -0.3894) were significantly correlated. The node efficiency and node degree of the right middle frontal gyrus (r = 0.4447 and 0.4539) and right pallidum (r = 0.4136 and 0.4501) significantly correlated with the MMSE score. DATA CONCLUSION: The brain network topology of CO poisoned children is damaged, which is manifested by reduced network integration and may lead to a series of clinical symptoms in patients. EVIDENCE LEVEL: 2. TECHNICAL EFFICACY: Stage 2.

Two similar carbon monoxide poisoning cases with different outcomes: evidence from longitudinal fMRI.

Prognosis after carbon monoxide (CO) poisoning is difficult to assess using structural images. Functional connectivity provided by functional magnetic resonance imaging (fMRI) may explain the mechanism of differential prognosis. We report here two cases of carbon monoxide poisoning with simultaneous coma. They were nearly normal on days 7-8, but diagnosed with delayed neurological sequelae (DNS) with cognitive and motor impairments on days 22-29. Similar Methylprednisolone pulse therapy and hyperbaric oxygen therapy were given to them. The movement disorder of case 1 improved slightly during the recovery stage, while the movement disorder of case 2 worsened significantly. In case 1, the function of supplementary motor area decreased first and then increased, and the function of pallidum increased first and then decreased. Case 2 showed a reduction in the supplementary motor area and small changes in the pallidum after DNS, but both were reduced during recovery stage. The cognitive ability of case 1 remained poor, while that of case 2 improved during the recovery stage. FMRI showed damage to the right and bilateral hippocampus in case 1 and partial damage to the left hippocampus in case 2. Taken together, fMRI can be a useful method to study functional connectivity abnormalities corresponding to different prognoses.

Early gray matter atrophy and neurological deficits in patients with carbon monoxide poisoning.

PURPOSE: To investigate early neurological deficits-related change patterns in gray matter (GM) volume in patients with carbon monoxide poisoning (COP) and GM volume differences between patients with and without delayed neurological sequelae (DNS) and those with and without T2 hyperintense lesions after COP. METHODS: Forty-one COP patients (24 patients with DNS) and 36 sex- and age-matched healthy controls (HC) were enrolled in this study. The neurological assessments were administered within 24 h after MRI scans. Voxel-based morphometry analysis was used to detect regional GM volume change. RESULTS: The COP group had statistically significant GM atrophy in the bilateral prefrontal and temporal lobes, anterior cingulate (ACC), thalamus, posterior cerebellum, and right hippocampus compared to the HC group. Atrophy in the left medial orbital superior frontal gyrus (SFG), bilateral ACC, and bilateral thalamus were related to lower Mini-Mental State Examination (MMSE) scores and higher Unified Parkinson's Disease Rating Scale subsection III and neuro-psychiatric inventory scores. Atrophy in the hippocampus and posterior cerebellum were also related to decrease MMSE scores. The DNS subgroup had greater GM atrophy in the limbic system than the non-DNS subgroup. Compared to the subgroup without T2 hyperintense lesions, greater GM atrophy in the limbic system, motor and visual cortex, and default network was observed in the subgroup with T2 hyperintense lesions. CONCLUSION: GM atrophy in the medial orbital SFG, ACC, thalamus, hippocampus, and posterior cerebellum is associated with early neurological deficits in patients with COP. Greater atrophy occurred in patients with DNS and those with T2 hyperintense lesions.

Trends in carbon monoxide poisoning deaths in high frequency hurricane states from 2014-19: the need for prevention intervention strategies.

INTRODUCTION: Hurricanes often result in power outages, which increase generator usage and carbon monoxide (CO) deaths. We aim to identify states with the highest frequency of hurricanes and evaluate the number of unintentional CO poisoning deaths by region, age, race and metropolitan distribution. METHODS: The number of hurricanes was determined using the FEMA database, and the number of unintentional CO poisoning deaths was determined using the CDC WONDER database from 2014-19. Hurricane-associated consumer outages were obtained from the Department of Energy. RESULTS: The number of unintentional CO poisoning deaths was as follows: Florida, South Carolina, North Carolina, Georgia and Alabama. Adults displayed a significantly higher number of unintentional CO poisoning deaths than pediatrics (P < 0.001). The total number of unintentional CO poisoning deaths was highest in the White population (P < 0.001); however, unintentional CO poisoning death rates were nearly two times higher among Black population in adults (0.5 versus 0.3) and pediatrics (0.2 versus 0.1). Medium metropolitan areas exhibited significantly more unintentional CO poisoning deaths (P < 0.001). CONCLUSIONS: Hurricanes and unintentional CO poisoning deaths were most common in Florida. Death rates were higher among Black individuals. Medium metropolitan areas displayed significantly more unintentional CO poisoning deaths than all other areas.

Optical, flow, and thermal analysis of a phototherapy extracorporeal membrane oxygenator for treating carbon monoxide poisoning.

BACKGROUND: Extracorporeal membrane oxygenators (ECMO) are currently utilized to mechanically ventilate blood when lung or lung and heart function are impaired, like in cases of acute respiratory distress syndrome (ARDS). ARDS can be caused by severe cases of carbon monoxide (CO) inhalation, which is the leading cause of poison-related deaths in the United States. ECMOs can be further optimized for severe CO inhalation using visible light to photo-dissociate CO from hemoglobin (Hb). In previous studies, we combined phototherapy with an ECMO to design a photo-ECMO device, which significantly increased CO elimination and improved survival in CO-poisoned animal models using light at 460, 523, and 620 nm wavelengths. Light at 620 nm was the most effective in removing CO. OBJECTIVE: The aim of this study is to analyze the light propagation at 460, 523, and 620 nm wavelengths and the 3D blood flow and heating distribution within the photo-ECMO device that increased CO elimination in CO-poisoned animal models. METHODS: Light propagation, blood flow dynamics, and heat diffusion were modeled using the Monte Carlo method and the laminar Navier-Stokes and heat diffusion equations, respectively. RESULTS: Light at 620 nm propagated through the device blood compartment (4 mm), while light at 460 and 523 nm only penetrated 48% to 50% (~2 mm). The blood flow velocity in the blood compartment varied with regions of high (5 mm/s) and low (1 mm/s) velocity, including stagnant flow. The blood temperatures at the device outlet for 460, 523, and 620 nm wavelengths were approximately 26.7°C, 27.4°C, and 20°C, respectively. However, the maximum temperatures within the blood treatment compartment rose to approximately 71°C, 77°C, and 21°C, respectively. CONCLUSIONS: As the extent of light propagation correlates with efficiency in photodissociation, the light at 620 nm is the optimal wavelength for removing CO from Hb while maintaining blood temperatures below thermal damage. Measuring the inlet and outlet blood temperatures is not enough to avoid unintentional thermal damage by light irradiation. Computational models can help eliminate risks of excessive heating and improve device development by analyzing design modifications that improve blood flow, like suppressing stagnant flow, further increasing the rate of CO elimination.

Extracorporeal membrane oxygenators with light-diffusing fibers for treatment of carbon monoxide poisoning: Experiments, mathematical modeling, and performance assessment with unit cells.

BACKGROUND AND OBJECTIVES: Approximately 50,000 emergency department visits per year due to carbon monoxide (CO) poisoning occur in the United States alone. Tissue hypoxia can occur at very low CO concentration exposures because CO binds with a 250-fold higher affinity than oxygen to hemoglobin. The most effective therapy is 100% hyperbaric oxygen (HBO) respiration. However, there are only a limited number of cases with ready accessibility to the specialized HBO chambers. In previous studies, we developed an extracorporeal veno-venous membrane oxygenator that facilitates exposure of blood to an external visible light source to photo-dissociate carboxyhemoglobin (COHb) and significantly increase CO removal from CO-poisoned blood (photo-extracorporeal veno-venous membrane oxygenator [p-ECMO]). One objective of this study was to describe in vitro experiments with different laser wavelength sources to compare CO elimination rates in a small unit-cell ECMO device integrated with a light-diffusing optical fiber. A second objective was to develop a mathematical model that predicts CO elimination rates in the unit-cell p-ECMO  device design upon which larger devices can be based. STUDY DESIGN/MATERIAL AND METHODS: Two small unit-cell p-ECMO devices consisted of a plastic capillary with a length and inside diameter of 10 cm and 1.15 mm, respectively. Either five (4-1 device) or seven (6-1 device) gas exchange tubes were placed in the plastic capillary and a light-diffusing fiber was inserted into one of the gas exchange tubes. Light from lasers emitting either 635 nm or 465 nm wavelengths was coupled into the light-diffusing fiber as oxygen flowed through the gas exchange membranes. To assess the ability of the device to remove CO from blood in vitro, the percent COHb reduction in a single pass through the device was assessed with and without light. The Navier Stokes equations, Carreau-Yesuda model, Boltzman equation for light distribution, and hemoglobin kinetic rate equations, including photo-dissociation, were combined in a mathematical model to predict COHb elimination in the experiments. RESULTS: For the unit-cell devices, the COHb removal rate increases with increased 635 nm laser power, increased blood time in the device, and greater gas exchange membrane surface-to-blood volume ratio. The 6-1 device COHb half-life versus that of the 4-1 device with 4 W at 635 nm light was 1.5 min versus 4.25 min, respectively. At 1 W laser power, 635 nm and 465 nm exhibited similar CO removal rates. The COHb half-life times of the 6-1 device were 1.25, 2.67, and 8.5 min at 635 nm (4 W), 465 nm (1 W), and 100% oxygen only, respectively. The mathematical model predicted the experimental results. An analysis of the in vivo COHb half-life of oxygen respiration therapy versus an adjunct therapy with a p-ECMO device and oxygen respiration shows a reduction from 90 min to as low as 10 min, depending on the device design. CONCLUSION: In this study, we experimentally studied and developed a mathematical model of a small unit-cell ECMO device integrated with a light-diffusing fiber illuminated with laser light. The unit-cell device forms the basis for a larger device and, in an adjunct therapy with oxygen respiration, has the potential to remove COHb at much higher rates than oxygen therapy alone. The mathematical model can be used to optimize the design in practical implementations to quickly and efficiently remove CO from CO-poisoned blood.

Prevalence and outcomes of rapidly progressive dementia: a retrospective cohort study in a neurologic unit in China.

BACKGROUND: Rapidly progressive dementia (RPD) is a syndrome originating from various diseases. Recent advances have allowed a better understanding of its categories and spectrum; however, it remains challenging to make an accurate differential diagnosis and prognosis prediction. METHODS: This study was a retrospective evaluation of all participants admitted to the neurology department of a single center in China from January 2015 to December 2019. The screened patients met the RPD criteria and their characteristics were collected to explore a diagnostic pattern of RPD. In addition, outcomes of RPD were evaluated with the Glasgow Outcome Scale (GOS), activities of daily living scale (ADL), and simplified Mini-Mental State Examination (MMSE), and different prognostic analysis methods were performed to determine the prognostic factors of RPD. RESULTS: A total of 149 RPD patients among 15,731 inpatients were identified with an average MMSE value of 13.0 ± 4.6 at baseline. Etiological epidemiology revealed infectious, neurodegenerative and toxic/metabolic diseases as the three largest groups, accounting for 26.2%, 20.8% and 16.8% of all cases, respectively. In particular, prevalence rates of Creutzfeldt-Jakob disease (13.4%), Alzheimer's disease (11.4%), carbon monoxide poisoning (8.1%), neurosyphilis (5.4%) and dementia with Lewy bodies (5.4%) were highest in this series. A recommended diagnostic framework for RPD etiology was thus established. Follow-up evaluations showed a negative correlation between age and GOS scores (r=-0.421, P < 0.001), as well as age and simplified MMSE scores (rs =- 0.393, P < 0.001), and a positive correlation between age and ADL scores (rs =0.503, P < 0.001), and significantly different GOS, ADL and simplified MMSE scores across various etiologies (P = 0.003; F = 9.463, P < 0.001; F = 6.117, P < 0.001). CONCLUSION: Infectious, neurodegenerative and toxic-metabolic entities were the most common RPD categories, and establishing a practical approach to RPD etiology would allow better disease management.

Development of a Nomogram Based on Diffusion-Weighted Imaging and Clinical Information to Predict Delayed Encephalopathy after Acute Carbon Monoxide Poisoning.

BACKGROUND: Delayed encephalopathy after acute carbon monoxide poisoning (DEACMP) is a severe complication that can arise from acute carbon monoxide poisoning (ACOP). This study aims to identify the independent risk factors associated with DEACMP and to develop a nomogram to predict the probability of developing DEACMP. METHODS: The data of patients diagnosed with ACOP between September 2015 and June 2021 were analyzed retrospectively. The patients were divided into the two groups: the DEACMP group and the non-DEACMP group. Univariate analysis and multivariate logistic regression analysis were conducted to identify the independent risk factors for DEACMP. Subsequently, a nomogram was constructed to predict the probability of DEACMP. RESULTS: The study included 122 patients, out of whom 30 (24.6%) developed DEACMP. The multivariate logistic regression analysis revealed that acute high-signal lesions on diffusion-weighted imaging (DWI), duration of carbon monoxide (CO) exposure, and Glasgow Coma Scale (GCS) score were independent risk factors for DEACMP (Odds Ratio = 6.230, 1.323, 0.714, p < 0.05). Based on these indicators, a predictive nomogram was constructed. CONCLUSIONS: This study constructed a nomogram for predicting DEACMP using high-signal lesions on DWI and clinical indicators. The nomogram may serve as a dependable tool to differentiate high-risk patients and enable the provision of personalized treatment to lower the incidence of DEACMP.

The effect of preconditioning agents on cardiotoxicity and neurotoxicity of carbon monoxide poisoning in animal studies: a systematic review.

BACKGROUND: Carbon monoxide (CO) poisoning is a common intoxication and many people die yearly due to CO poisoning and preconditioning agents attenuate brain and cardiac injury caused by intoxication. It is critical to fully understand the efficacy of new methods to directly target the toxic effect of CO, such as conditioning agents, which are currently under development. This study aims to systematically investigate current evidence from animal experiments and the effects of administration preconditions in acute and late phases after CO poisoning on cardiotoxicity and neurotoxicity. METHODS: Four databases (PubMed, Embase, Scopus, and Web of Science) were systematically searched without language restrictions, and hand searching was conducted until November 2021. We included studies that compare preconditioning agents with the control group after CO poisoning in animals. The SYRCLE RoB tool was used for risk of bias assessments. RESULTS: Thirty-seven studies were included in the study. Erythropoietin, granulocyte colony-stimulating factor (GCSF), hydrogen-rich saline, and N-butylphthalide (NBP) were found to have positive effects on reducing neurotoxicity and cardiotoxicity. As other preconditions have fewer studies, no valuable results can be deduced. Most of the studies were unclear for sources of bias. DISCUSSION: Administration of the examined preconditioning agents including NBP, hydrogen-rich saline, and GCSF in acute and late phases could attenuate neurotoxicity and cardiotoxicity of CO poisoned animals. For a better understanding of mechanisms and activities, and finding new and effective preconditioning agents, further preclinical and clinical studies should be performed to analyze the effects of preconditioning agents.