Explainable Deep Learning Model for Predicting Serious Adverse Events in Hospitalized Geriatric Patients Within 72 Hours.

Background: The global aging population presents a significant challenge, with older adults experiencing declining physical and cognitive abilities and increased vulnerability to chronic diseases and adverse health outcomes. This study aims to develop an interpretable deep learning (DL) model to predict adverse events in geriatric patients within 72 hours of hospitalization. Methods: The study used retrospective data (2017-2020) from a major medical center in Taiwan. It included non-trauma geriatric patients who visited the emergency department and were admitted to the general ward. Data preprocessing involved collecting prognostic factors like vital signs, lab results, medical history, and clinical management. A deep feedforward neural network was developed, and performance was evaluated using accuracy, sensitivity, specificity, positive predictive value (PPV), and area under the receiver operating characteristic curve (AUC). Model interpretation utilized the Shapley Additive Explanation (SHAP) technique. Results: The analysis included 127,268 patients, with 2.6% experiencing imminent intensive care unit transfer, respiratory failure, or death during hospitalization. The DL model achieved AUCs of 0.86 and 0.84 in the validation and test sets, respectively, outperforming the Sequential Organ Failure Assessment (SOFA) score. Sensitivity and specificity values ranged from 0.79 to 0.81. The SHAP technique provided insights into feature importance and interactions. Conclusion: The developed DL model demonstrated high accuracy in predicting serious adverse events in geriatric patients within 72 hours of hospitalization. It outperformed the SOFA score and provided valuable insights into the model's decision-making process.

Association between organophosphate flame retardant exposure and lipid metabolism: data from the 2013-2014 National Health and Nutrition Examination Survey.

Organophosphate flame retardants (OPFRs) are emerging environmental pollutants that can be detected in water, dust, and biological organisms. Certain OPFRs can disrupt lipid metabolism in animal models and cell lines. However, the effects of OPFRs on human lipid metabolism remain unclear. We included 1,580 participants (≥20 years) from the 2013-2014 National Health and Nutrition Examination Survey (NHANES) to explore the relationship between OPFR exposure and lipid metabolism biomarkers. After adjusting for confounding factors, results showed that one-unit increases in the log levels of diphenyl phosphate (DPhP) (regression coefficient = -5.755; S.E. = 2.289; p = 0.023) and log bis-(1-chloro-2-propyl) phosphate (BCPP) (regression coefficient = -4.637; S.E. = 2.019; p = 0.036) were negatively associated with the levels of total cholesterol (TC) in all participants. One-unit increases in the levels of DPhP (regression coefficient = -2.292; S.E. = 0.802; p = 0.012), log bis (1,3-dichloro-2-propyl) phosphate (BDCPP) (regression coefficient = -2.046; S.E. = 0.825; p = 0.026), and log bis-2-chloroethyl phosphate (BCEP) (regression coefficient = -2.604; S.E. = 0.704; p = 0.002) were negatively associated with the levels of high-density lipoprotein cholesterol (HDL-C). With increasing quartiles of urine BDCPP levels, the mean TC levels significantly decreased in all participants (p value for trend = 0.028), and quartile increases in the levels of DPhP (p value for trend = 0.01), BDCPP (p value for trend = 0.001), and BCEP (p value for trend<0.001) were negatively corelated with HDL-C, with approximately 5.9, 9.9, and 12.5% differences between the upper and lower quartiles. In conclusion, DPhP, BDCPP, and BCEP were negatively related to HDL-C concentration, whereas DPhP and BCPP levels were negatively associated with TC level. Thus, exposure to OPFRs may interfere with lipid metabolism.

Levels of organophosphate flame retardants and their metabolites among 391 volunteers in Taiwan: difference between adults and children.

Background: Organophosphate flame retardants (OPFRs) are ubiquitous in the environment. The compositions and concentrations of different OPFRs metabolites vary in different environments depending on different human activities. The objective of the present study was to evaluate the exposure of different age groups to OPFRs in Taiwan. Methods: Volunteers provided urine samples and responded to questionnaires including demographic factors, underlying disease, lifestyle information, and occupation from October 2021 to January 2022. OPFR measurements were performed using a Waters Acquity Ultra-Performance Liquid Chromatography system coupled with a Waters Xevo TQ-XS mass spectrometer. Results: A total of 391 volunteers (74 children and 317 adults) were enrolled in this study. The concentrations (presented as µg/g creatinine) of bis(1,3-dichloro-2-propyl) phosphate (BDCPP, p = 0.029) and tri-n-butyl phosphate (TNBP, p = 0.008) were higher in the adult group, while the concentrations of bis-2-chloroethyl phosphate (BCEP, p = 0.024), diphenyl phosphate (DPHP, p < 0.001), tris(1,3-dichloro-2-propyl) phosphate (TDCPP, p = 0.009), and Tris(2-butoxyethyl) phosphate (TBEP, p = 0.007) were higher in the child group. Compared with school age children (>6 years), the concentration of di(2-n-butoxyethyl) phthalate (DBEP, 1.14 vs. 0.20 µg/g creatinine, p = 0.001), DPHP (1.23 vs. 0.54 µg/g creatinine, p = 0.036), TBEP (1.63 vs. 0.29 µg/g creatinine, p < 0.001), and the sum of OPFR metabolites (ΣOPFRs, 6.58 vs. 2.04 µg/g creatinine, p < 0.001) were statistically higher in preschool-aged children. After adjusting for confounding factors, pre-school age [odds ratio (OR): 4.579, 95% confidence interval (CI): 1.389-13.115] and current smoker (OR: 5.328, 95%CI: 1.858-14.955) were independently associated with the risk of ΣOPFRs higher than 90 percentile. Conclusion: This study revealed the distribution of different OPFRs metabolites in children and adults. DBEP, DPHP, TBEP, and ΣOPFR were higher in preschool-aged children. Pre-school age and current smoking status were independent risk factors for ΣOPFRs higher than 90 percentile.

Use of a Deep-Learning Algorithm to Guide Novices in Performing Focused Assessment With Sonography in Trauma.

This quality improvement study compares the diagnostic quality and completion time between ultrasonography operators guided by artificial intelligence vs those without such assistance.

Ambient Air Pollution and Risk for Stroke Hospitalization: Impact on Susceptible Groups.

Stroke is a leading cause of death, and air pollution is associated with stroke hospitalization. However, the susceptibility factors are unclear. Retrospective studies from 2014 to 2018 in Kaohsiung, Taiwan, were analyzed. Adult patients (>17 years) admitted to a medical center with stroke diagnosis were enrolled and patient characteristics and comorbidities were recorded. Air pollutant measurements, including those of particulate matter (PM) with aerodynamic diameters < 10 µm (PM10) and < 2.5 µm (PM2.5), nitrogen dioxide (NO2), and ozone (O3), were collected from air quality monitoring stations. During the study period, interquartile range (IQR) increments in PM2.5 on lag3 and lag4 were 12.3% (95% CI, 1.1−24.7%) and 11.5% (95% CI, 0.3−23.9%) concerning the risk of stroke hospitalization, respectively. Subgroup analysis revealed that the risk of stroke hospitalization after exposure to PM2.5 was greater for those with advanced age (≥80 years, interaction p = 0.045) and hypertension (interaction p = 0.034), after adjusting for temperature and humidity. A dose-dependent effect of PM2.5 on stroke hospitalization was evident. This is one of few studies focusing on the health effects of PM2.5 for patients with risk factors of stroke. We found that patients with risk factors, such as advanced age and hypertension, are more susceptible to PM2.5 impacts on stroke hospitalization.

Exposure to tris(2-butoxyethyl) phosphate induces abnormal sperm morphology and testicular histopathology in male rats.

Tris(2-butoxyethyl) phosphate (TBEP) is one of the most abundant organophosphate flame retardants in the environment. This study aimed to evaluate the effect of TBEP exposure during adolescence on male reproductive function in adult rats. Male Sprague-Dawley rats were treated with 20 and 200 mg/kg body weight of TBEP or corn oil from postnatal day (PND) 42 to PND 105. A significant increase in the proportion of sperm with abnormal morphology (flattened head and bent tail) and superoxide anion (O2-.) production in the sperm of the 200 mg/kg treated group was observed (p < 0.05). Excessive production of sperm hydrogen peroxide (H2O2) was found in both the 20 and 200 mg/kg treatment groups (p < 0.05). Disruption of testicular structure was observed in the 20 and 200 mg/kg treated groups and seminiferous tubule degeneration was observed in the 200 mg/kg treated group. Our study demonstrated the adverse effects of TBEP on male reproductive function in rats.

Experience of carbon monoxide poisoning and the outcome predicting score: A multicenter retrospective study.

BACKGROUND: Carbon monoxide poisoning (COP), resulting from accidental and intentional exposure, is a leading cause of fatal poisoning worldwide. Except for early death, neurological sequelae are common and impose a large burden on patients, caregivers, and the society. MATERIALS AND METHODS: This retrospective study included patients who visited the emergency departments (EDs) of the medical institutes of Chang Gung Memorial Hospital after COP with a carboxyhemoglobin level > 10% between January 2009 and October 2018. Patients who experienced out-of-hospital cardiac arrest (OHCA) were excluded. Poor outcome was defined as mortality or a Glasgow coma scale (GCS) <13 at discharge. Stepwise regression analysis was performed, and a receiver operating characteristic (ROC) curve was applied to analyze our newly created scoring system for prognosis prediction. RESULTS: This study enrolled 1171 patients. Fire scene (F) (aOR, 20.635; 95% CI, 8.345-51.023), intentional CO exposure (I) (aOR, 2.634; 95% CI, 1.335-5.196), respiratory failure (R) (aOR, 9.944; 95% CI, 5.533-17.873), every point of reduced GCS (E) (aOR, 1.253; 95% CI, 1.186-1.323), and diabetes mellitus (D) (aOR, 2.749; 95% CI, 1.201-6.292) were identified as predictors of poor outcomes. The FIRED score was created. CONCLUSION: The FIRED score could predict the outcomes of non-OHCA patients with a carboxyhemoglobin level > 10% after COP using five factors that can be obtained by history taking and basic examination. An FIRED score ≥ 10 was associated with a poor outcome (sensitivity, 89.6%; specificity, 82.4%; AUC0.930).

Association between Ambient Air Pollution and Emergency Room Visits for Pediatric Respiratory Diseases: The Impact of COVID-19 Pandemic.

The level and composition of air pollution have changed during the coronavirus disease 2019 (COVID-19) pandemic. However, the association between air pollution and pediatric respiratory disease emergency department (ED) visits during the COVID-19 pandemic remains unclear. The study was retrospectively conducted between 2017 and 2020 in Kaohsiung, Taiwan, from 1 January 2020 to 1 May 2020, defined as the period of the COVID-19 pandemic, and 1 January 2017 to 31 May 2019, defined as the pre-COVID-19 pandemic period. We enrolled patients under 17 years old who visited the ED in a medical center and were diagnosed with respiratory diseases such as pneumonia, asthma, bronchitis, and acute pharyngitis. Measurements of particulate matter (PM) with aerodynamic diameters of <10 µm (PM10) and < 2.5 µm (PM2.5), nitrogen dioxide (NO2), and Ozone (O3) were collected. During the COVID-19 pandemic, an increase in the interquartile range of PM2.5, PM10, and NO2 levels was associated with increases of 72.5% (95% confidence interval [CI], 50.5−97.7%), 98.0% (95% CI, 70.7−129.6%), and 54.7% (95% CI, 38.7−72.6%), respectively, in the risk of pediatric respiratory disease ED visits on lag 1, which were greater than those in the pre-COVID-19 pandemic period. After adjusting for temperature and humidity, the risk of pediatric respiratory diseases after exposure to PM2.5 (inter p = 0.001) and PM10 (inter p < 0.001) was higher during the COVID-19 pandemic. PM2.5, PM10, and NO2 may play important roles in pediatric respiratory events in Kaohsiung, Taiwan. Compared with the pre-COVID-19 pandemic period, the levels of PM2.5 and PM10 were lower; however, the levels were related to a greater increase in ED during the COVID-19 pandemic.

Deep Learning Assisted Detection of Abdominal Free Fluid in Morison's Pouch During Focused Assessment With Sonography in Trauma.

Background: The use of focused assessment with sonography in trauma (FAST) enables clinicians to rapidly screen for injury at the bedsides of patients. Pre-hospital FAST improves diagnostic accuracy and streamlines patient care, leading to dispositions to appropriate treatment centers. In this study, we determine the accuracy of artificial intelligence model-assisted free-fluid detection in FAST examinations, and subsequently establish an automated feedback system, which can help inexperienced sonographers improve their interpretation ability and image acquisition skills. Methods: This is a single-center study of patients admitted to the emergency room from January 2020 to March 2021. We collected 324 patient records for the training model, 36 patient records for validation, and another 36 patient records for testing. We balanced positive and negative Morison's pouch free-fluid detection groups in a 1:1 ratio. The deep learning (DL) model Residual Networks 50-Version 2 (ResNet50-V2) was used for training and validation. Results: The accuracy, sensitivity, and specificity of the model performance for ascites prediction were 0.961, 0.976, and 0.947, respectively, in the validation set and 0.967, 0.985, and 0.913, respectively, in the test set. Regarding feedback prediction, the model correctly classified qualified and non-qualified images with an accuracy of 0.941 in both the validation and test sets. Conclusions: The DL algorithm in ResNet50-V2 is able to detect free fluid in Morison's pouch with high accuracy. The automated feedback and instruction system could help inexperienced sonographers improve their interpretation ability and image acquisition skills.

Effects of Fine Particulate Matter and Its Components on Emergency Room Visits for Pediatric Pneumonia: A Time-Stratified Case-Crossover Study.

Pneumonia, one of the important causes of death in children, may be induced or aggravated by particulate matter (PM). Limited research has examined the association between PM and its constituents and pediatric pneumonia-related emergency department (ED) visits. Measurements of PM2.5, PM10, and four PM2.5 constituents, including elemental carbon (EC), organic carbon (OC), nitrate, and sulfate, were extracted from 2007 to 2010 from one core station and two satellite stations in Kaohsiung City, Taiwan. Furthermore, the medical records of patients under 17 years old who had visited the ED in a medical center and had a diagnosis of pneumonia were collected. We used a time-stratified, case-crossover study design to estimate the effect of PM. The single-pollutant model demonstrated interquartile range increase in PM2.5, PM10, nitrate, OC, and EC on lag 3, which increased the risk of pediatric pneumonia by 18.2% (95% confidence interval (Cl), 8.8-28.4%), 13.1% (95% CI, 5.1-21.7%), 29.7% (95% CI, 16.4-44.5%), 16.8% (95% CI, 4.6-30.4%), and 14.4% (95% Cl, 6.5-22.9%), respectively. After PM2.5, PM10, and OC were adjusted for, nitrate and EC remained significant in two-pollutant models. Subgroup analyses revealed that nitrate had a greater effect on children during the warm season (April to September, interaction p = 0.035). In conclusion, pediatric pneumonia ED visit was related to PM2.5 and its constituents. Moreover, PM2.5 constituents, nitrate and EC, were more closely associated with ED visits for pediatric pneumonia, and children seemed to be more susceptible to nitrate during the warm season.

Assessment of glufosinate-containing herbicide exposure: A multi-center retrospective study.

BACKGROUND: Exposure to glufosinate ammonium, an herbicide used worldwide, can cause CNS and respiratory toxicities. This study aimed to analyze acute human glufosinate ammonium poisoning. MATERIALS AND METHODS: This multicenter retrospective cohort study involved five medical institutes affiliated with the Chang Gung Memorial Hospital system. Patients with glufosinate ammonium exposure visiting the emergency department (ED) between January 2008 and December 2020 were included. RESULTS: In total, 95 patients were enrolled. Compared to exposure via the non-oral route, patients exposed orally (n = 61) had lower GCS scores, higher mortality rates, and longer hospital lengths of stay (P-value: <0.001, 0.002, and < 0.001, respectively). In the subgroup analysis among oral exposure patients, the survival group had a lower amount of estimated glufosinate ingestion than the non-survival group (10.5 [3.4-27] vs. 40.5 [27-47.3] g, P-value: 0.022), lower rate of substance co-exposure (9 [19.6%] vs. 10 [66.7%] P-value: 0.001), and lower rate of paraquat co-exposure (0 [0%] vs. 7 [46.7%] P < 0.001) compared with the mortality group. In the orally-exposed and non-paraquat co-exposure patients (n = 54), age > 70 years and GCS score < 9 at triage presented a high sensitivity (100.00%, 95% CI: 63.06-100.00%) and medium specificity (58.70%, 95% CI: 43.23-73.00%) in predicting mortality. CONCLUSION: Old age, change in consciousness, and paraquat co-exposure were associated with higher mortality in human glufosinate poisoning. Age > 70 years and GCS score < 9 at triage could be predictors of mortality in patients with acute oral glufosinate poisoning.

Impact of coronary risk scores on disposition decision in emergency patients with chest pain.

BACKGROUND: Coronary risk scores (CRS) including History, Electrocardiogram, Age, Risk Factors, Troponin (HEART) score and Emergency Department Assessment of Chest pain Score (EDACS) can help identify patients at low risk of major adverse cardiac events. In the emergency department (ED), there are wide variations in hospital admission rates among patients with chest pain. OBJECTIVE: This study aimed to evaluate the impact of CRS on the disposition of patients with symptoms suggestive of acute coronary syndrome in the ED. METHODS: This retrospective cohort study included 3660 adult patients who presented to the ED with chest pain between January and July in 2019. Study inclusion criteria were age > 18 years and a primary position International Statistical Classification of Diseases and Related Health Problems-10th revision coded diagnosis of angina pectoris (I20.0-I20.9) or chronic ischemic heart disease (I25.0-I25.9) by the treating ED physician. If the treating ED physician completed the electronic structured variables for CRS calculation to assist disposition planning, then the patient would be classified as the CRS group; otherwise, the patient was included in the control group. RESULTS: Among the 2676 patients, 746 were classified into the CRS group, whereas the other 1930 were classified into the control group. There was no significant difference in sex, age, initial vital signs, and ED length of stay between the two groups. The coronary risk factors were similar between the two groups, except for a higher incidence of smokers in the CRS group (19.6% vs. 16.1%, p = 0.031). Compared with the control group, significantly more patients were discharged (70.1% vs. 64.6%) directly from the ED, while fewer patients who were hospitalized (25.9% vs. 29.7%) or against-advise discharge (AAD) (2.6% vs. 4.0%) in the CRS group. Major adverse cardiac events and mortality at 60 days between the two groups were not significantly different. CONCLUSIONS: A higher ED discharge rate of the group using CRS may indicate that ED physicians have more confidence in discharging low-risk patients based on CRS.

Autonomic Dysfunction Contributes to Impairment of Cerebral Autoregulation in Patients with Epilepsy.

Patients with epilepsy frequently experience autonomic dysfunction and impaired cerebral autoregulation. The present study investigates autonomic function and cerebral autoregulation in patients with epilepsy to determine whether these factors contribute to impaired autoregulation. A total of 81 patients with epilepsy and 45 healthy controls were evaluated, assessing their sudomotor, cardiovagal, and adrenergic functions using a battery of autonomic nervous system (ANS) function tests, including the deep breathing, Valsalva maneuver, head-up tilting, and Q-sweat tests. Cerebral autoregulation was measured by transcranial Doppler examination during the breath-holding test, the Valsalva maneuver, and the head-up tilting test. Autonomic functions were impaired during the interictal period in patients with epilepsy compared to healthy controls. The three indices of cerebral autoregulation-the breath-holding index (BHI), an autoregulation index calculated in phase II of the Valsalva maneuver (ASI), and cerebrovascular resistance measured in the second minute during the head-up tilting test (CVR2-min)-all decreased in patients with epilepsy. ANS dysfunction correlated significantly with impairment of cerebral autoregulation (measured by BHI, ASI, and CVR2-min), suggesting that the increased autonomic dysfunction in patients with epilepsy may augment the dysregulation of cerebral blood flow. Long-term epilepsy, a high frequency of seizures, and refractory epilepsy, particularly temporal lobe epilepsy, may contribute to advanced autonomic dysfunction and impaired cerebral autoregulation. These results have implications for therapeutic interventions that aim to correct central autonomic dysfunction and impairment of cerebral autoregulation, particularly in patients at high risk for sudden, unexplained death in epilepsy.

Association between liberal oxygen therapy and mortality in patients with paraquat poisoning: A multi-center retrospective cohort study.

Paraquat (N, N'-dimethyl-4, 4'-bipyridinium dichloride, PQ) intoxication is a common cause of lethal poisoning. This study aimed to identify the risk of using liberal oxygen therapy in patients with PQ poisoning. This was a multi-center retrospective cohort study involving four medical institutions in Taiwan. Data were extracted from the Chang Gung Research Database (CGRD) from January 2004 to December 2016. Patients confirmed to have PQ intoxication with a urine PQ concentration ≥ 5 ppm were analyzed. Patients who received oxygen therapy before marked hypoxia (SpO2 ≥ 90%) were defined as receiving liberal oxygen therapy. The association between mortality and patient demographics, blood paraquat concentration (ppm), and liberal oxygen therapy were analyzed. A total of 416 patients were enrolled. The mortality rate was higher in the liberal oxygen therapy group (87.8% vs. 73.7%, P = 0.007), especially in 28-day mortality (adjusted odds ratio [aOR]: 4.71, 95% confidence interval [CI]: 1.533-14.471) and overall mortality (aOR: 5.97, 95% CI: 1.692-21.049) groups. Mortality in patients with PQ poisoning was also associated with age (aOR: 1.04, 95% CI: 1.015-1.073), blood creatinine level (aOR: 1.49, 95% CI: 1.124-1.978), and blood paraquat concentration (ppm) (aOR, 1.51; 95% CI: 1.298-1.766). Unless the evidence of hypoxia (SpO2 < 90%) is clear, oxygen therapy should be avoided because it is associated with increased mortality.

Physicians' Risk Tolerance and Head Computed Tomography Use for Pediatric Patients With Minor Head Injury.

OBJECTIVES: Traumatic brain injury is the leading cause of death and disability in children worldwide. The objective of this study was to determine the association between physician risk tolerance and head computed tomography (CT) use in patients with minor head injury (MHI) in the emergency department (ED). METHODS: We retrospectively analyzed pediatric patients (<17 years old) with MHI in the ED and then administered 2 questionnaires (a risk-taking subscale [RTS] of the Jackson Personality Inventory and a malpractice fear scale [MFS]) to attending physicians who had evaluated these patients and made decisions regarding head CT use. The primary outcome was head CT use during ED evaluation; the secondary outcome was ED length of stay and final diagnosis of intracranial injury (ICI). RESULTS: Of 523 patients with MHI, 233 (44.6%) underwent brain CT, and 16 (3.1%) received a final diagnosis of ICI. Among the 16 emergency physicians (EPs), the median scores of the MFS and RTS were 22 (interquartile range, 17-26) and 23 (interquartile range, 19-25), respectively. Emergency physicians who were most risk averse tended to order more head CT scans compared with the more risk-tolerant EPs (56.96% vs 37.37%; odds ratio, 8.463; confidence interval, 2.783-25.736). The ED length of stay (P = 0.442 and P = 0.889) and final diagnosis (P = 0.155 and P = 0.835) of ICI were not significantly associated with the RTS and MFS scores. CONCLUSIONS: Individual EP risk tolerance, as measured by RTS, was predictive of CT use in pediatric patients with MHI.

Benefits of Early In-Hospital Antivenom Administration to Patients with Protobothrops mucrosquamatus Envenomation.

Protobothrops mucrosquamatus is one of the common venomous snakes in Southeast Asia. This retrospective cohort study conducted in six medical institutions in Taiwan aimed to obtain information on the optimal management strategies for P. mucrosquamatus snakebite envenomation. Data were extracted from the Chang Gung Research Database from January 2006 to December 2016. The association between early antivenom administration and patient demographics, pain requiring treatment with analgesic injections, and hospital length of stay was analyzed. A total of 195 patients were enrolled; 130 were administered antivenom within 1 hour after emergency department arrival (early group), whereas 65 were treated later than 1 hour after arrival (late group). No in-hospital mortality was identified. The difference in surgical intervention rates between the early and late groups was statistically insignificant (P = 0.417). Compared with the early group, the late group showed a higher rate of antivenom skin test performance (46.9% versus 63.1%, respectively, P = 0.033), longer hospital stay (42 ± 62 hours versus 99 ± 70 hours, respectively, P = 0.016), and higher rate of incidences of pain requiring treatment with analgesic injections (29.2% versus 46.2%, respectively, P = 0.019). After adjusting for confounding factors, early antivenom administration was associated with decreased pain requiring treatment with analgesic injections (adjusted odds ratio: 0.51, 95% CI: 0.260-0.985). Antivenom administration within 1 hour of arrival was associated with a decreased likelihood of experiencing pain and hospital length of stay in patients with P. mucrosquamatus snakebites. Antivenom skin testing was associated with delays in antivenom administration.

Serum Levels of Soluble Triggering Receptor Expressed on Myeloid Cells-1 Associated with the Severity and Outcome of Acute Ischemic Stroke.

Stroke is a neurological emergency, where the mechanism of the blood supply to the brain is impaired, resulting in brain cell ischemia and death. Neuroinflammation is a key component in the ischemic cascade that results in cell damage and death after cerebral ischemia. The triggering receptor expressed on myeloid cells-1 (TREM-1) modulates neuroinflammation after acute ischemic stroke. In the present study, 60 patients with acute ischemic stroke, who had been subjected to neurological examinations and National Institutes of Health Stroke Scale (NIHSS) and brain magnetic resonance imaging studies, were enrolled in the emergency room of Kaohsiung Chang Gung Memorial Hospital. Twenty-four healthy volunteers were recruited as controls. The serum levels of soluble TREM-1 (sTREM-1), human S100 calcium-binding protein B (S100B), and proinflammatory cytokines and chemokines, including tumor necrosis α (TNF-α), interleukin 1ß, interleukin 6 (IL-6), interleukin 8, and interferon-γ were measured immediately after acute ischemic stroke. The serum levels of sTREM-1, TNFα, IL-6, and S100B were correlated with the stroke volume and NIHSS, after acute ischemic stroke. Additionally, the serum levels of sTREM-1 were significantly positively correlated with S100B. The functional outcomes were evaluated 6 months after ischemic stroke by the Barthel index, which was correlated with the age and levels of sTREM-1 and S100B. We suggest that acute ischemic stroke induces neuroinflammation by the activation of the TREM-1 signaling pathway and the downstream inflammatory machinery that modulates the inflammatory response and ischemic neuronal cell death. From a translational perspective, our results may allow for the development of a new therapeutic strategy for acute ischemic stroke by targeting the TREM-1 signaling pathway.

Peroxisome Proliferator-Activated Receptor γ Coactivator 1α Activates Vascular Endothelial Growth Factor That Protects Against Neuronal Cell Death Following Status Epilepticus through PI3K/AKT and MEK/ERK Signaling.

Status epilepticus may cause molecular and cellular events, leading to hippocampal neuronal cell death. Peroxisome proliferator-activated receptor γ coactivator 1-α (PGC-1α) is an important regulator of vascular endothelial growth factor (VEGF) and VEGF receptor 2 (VEGFR2), also known as fetal liver kinase receptor 1 (Flk-1). Resveratrol is an activator of PGC-1α. It has been suggested to provide neuroprotective effects in epilepsy, stroke, and neurodegenerative diseases. In the present study, we used microinjection of kainic acid into the left hippocampal CA3 region in Sprague Dawley rats to induce bilateral prolonged seizure activity. Upregulating the PGC-1α pathway will increase VEGF/VEGFR2 (Flk-1) signaling and further activate some survival signaling that includes the mitogen activated protein kinase kinase (MEK)/mitogen activated protein kinase (ERK) and phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling pathways and offer neuroprotection as a consequence of apoptosis in the hippocampal neurons following status epilepticus. Otherwise, downregulation of PGC-1α by siRNA against pgc-1α will inhibit VEGF/VEGFR2 (Flk-1) signaling and suppress pro-survival PI3K/AKT and MEK/ERK pathways that are also accompanied by hippocampal CA3 neuronal cell apoptosis. These results may indicate that the PGC-1α induced VEGF/VEGFR2 pathway may trigger the neuronal survival signaling, and the PI3K/AKT and MEK/ERK signaling pathways. Thus, the axis of PGC-1α/VEGF/VEGFR2 (Flk-1) and the triggering of downstream PI3K/AKT and MEK/ERK signaling could be considered an endogenous neuroprotective effect against apoptosis in the hippocampus following status epilepticus.

Circulating MicroRNAs from Serum Exosomes May Serve as a Putative Biomarker in the Diagnosis and Treatment of Patients with Focal Cortical Dysplasia.

Focal cortical dysplasia (FCD) is a congenital malformation of cortical development where the cortical neurons located in the brain area fail to migrate in the proper formation. Epilepsy, particularly medically refractory epilepsy, is the most common clinical presentation for all types of FCD. This study aimed to explore the expression change of circulating miRNAs in patients with FCD from serum exosomes. A total of nine patients with FCD and four healthy volunteers were enrolled in this study. The serum exosomes were isolated from the peripheral blood of the subjects. Transmission electron microscopy (TEM) was used to identify the exosomes. Both exosomal markers and neuronal markers were detected by Western blotting analysis to prove that we could obtain central nervous system-derived exosomes from the circulation. The expression profiles of circulating exosomal miRNAs were assessed using next-generation sequencing analysis (NGS). We obtained a total of 107 miRNAs with dominant fold change (>2-fold) from both the annotated 5p-arm and 3p-arm of 2780 mature miRNAs. Based on the integrated platform of HMDD v3.2, miRway DB and DIANA-miRPath v3.0 online tools, and confirmed by MiRBase analysis, four potentially predicted miRNAs from serum exosomes in patients with FCD were identified, including miR194-2-5p, miR15a-5p, miR-132-3p, and miR-145-5p. All four miRNAs presented upregulated expression in patients with FCD compared with controls. Through Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis and pathway category of four target miRNAs, we found eight possible signaling pathways that may be related to FCD. Among them, we suggest that the mTOR signaling pathway, PI3K-Akt signaling pathway, p53 signaling pathway, and cell cycle regulation and TGF-beta signaling pathway are high-risk pathways that play a crucial role in the pathogenesis of FCD and refractory epilepsy. Our results suggest that the circulating miRNAs from exosomes may provide a potential biomarker for diagnostic, prognostic, and therapeutic adjuncts in patients with FCD and refractory epilepsy.

The Ottawa subarachnoid hemorrhage clinical decision rule for classifying emergency department headache patients.

BACKGROUND: Subarachnoid hemorrhage (SAH) is a serious cause of headaches. The Ottawa subarachnoid hemorrhage (OSAH) rule helps identify SAH in patients with acute nontraumatic headache with high sensitivity, but provides limited information for identifying other intracranial pathology (ICP). OBJECTIVES: To assess the performance of the OSAH rule in emergency department (ED) headache patients and evaluate its impact on the diagnosis of intracranial hemorrhage (ICH) and other ICP. METHOD: We conducted a retrospective cohort study from January 2016 to March 2017. Patients with acute headache with onset within 14 days of the ED visit, were included. We excluded patients with head trauma that occurred in the previous 7 days, new onset of abnormal neurologic findings, or consciousness disturbance. According to the OSAH rule, patients with any included predictors required further investigation. RESULTS: Of 913 patients were included, 15 of them were diagnosed with SAH. The OSAH rule had 100% (95% CI, 78.2%-100%) sensitivity and 37.0% (95% CI, 33.8-40.2%) specificity for identifying SAH. Twenty-two cases were identified as SAH or ICH with 100% sensitivity (95% CI, 84.6%-100%) and 37.3% (95% CI, 34.1%-40.5%) specificity. As for non-hemorrhagic ICP, both the sensitivity and negative predictive values (NPV) decreased to 75.0% (95% CI, 53.3%-90.2%) and 98.2% (95% CI, 96.1%-99.3%), respectively. CONCLUSIONS: The OSAH rule had 100% sensitivity and NPV for diagnosing SAH and ICH with acute headache. The sensitivity and specificity were lower for non-hemorrhagic ICP. The OSAH rule may be an effective tool to exclude acute ICH and SAH in our setting.