The pathophysiology of sepsis is characterized by a systemic inflammatory response to infection; however, the cytokine blockade that targets a specific early inflammatory mediator, such as tumor necrosis factor, has shown disappointing results in clinical trials. During sepsis, excessive endotoxins are internalized into the cytoplasm of immune cells, resulting in dysregulated pyroptotic cell death, which induces the leakage of late mediator alarmins such as HMGB1 and PTX3. As late mediators of lethal sepsis, overwhelming amounts of alarmins bind to high-affinity TLR4/MD2 and low-affinity RAGE receptors, thereby amplifying inflammation during early-stage sepsis. In this study, we developed a novel alarmin/receptor-targeting system using a TLR4/MD2/RAGE-blocking peptide (TMR peptide) derived from the HMGB1/PTX3-receptors interacting motifs. The TMR peptide successfully attenuated HMGB1/PTX3- and LPS-mediated inflammatory cytokine production by impairing its interactions with TLR4 and RAGE. Moreover, we developed TMR peptide-conjugated liposomes (TMR-Lipo) to improve the peptide pharmacokinetics. In combination therapy, moderately antibiotic-loaded TMR-Lipo demonstrated a significant therapeutic effect in a mouse model of cecal ligation- and puncture-induced sepsis. The identification of these peptides will pave the way for the development of novel pharmacological tools for sepsis therapy.

Background: and Purpose Spinocerebellar ataxias (SCAs) are the most common form of hereditary ataxias. Extracerebellar signs have been well described and are helpful in differentiating the SCA subtypes. However, there are few reports on the early-stage extracerebellar signs in various SCA subtypes. This study explored the clinical and magnetic resonance imaging (MRI) characteristics of early-stage SCAs in the Korean population. Methods: We retrospectively reviewed the medical records of genetically confirmed SCA patients with a disease duration of <5 years. Data on baseline characteristics, extracerebellar signs, and initial MRI findings were organized based on SCA subtypes. Results: This study included 117 SCA patients with a median age at onset of 40.6 years. The family history was positive in 71.8% of the patients, and the median disease duration and the score on the Scale for the Assessment and Rating of Ataxia at the initial visit were 2.6 years and 5.0, respectively. SCA3 was the most prevalent subtype, and oculomotor abnormalities were the most frequent extracerebellar signs in early-stage SCAs. Saccadic slowing was characteristic of SCA2 and SCA7, and gaze-evoked nystagmus was prominent in SCA6. Parkinsonism was relatively frequent in SCA8 and SCA3. Decreased visual acuity was specific for SCA7. Dementia was not an early manifestation of SCAs. Brain MRI revealed a pattern of pontocerebellar atrophy in SCA2 and SCA7, while SCA6 demonstrated only cerebellar cortical atrophy. Conclusions SCA patients exhibited diverse extracerebellar signs even in the early stage.Specific extracerebellar signs were characteristic of specific subtypes, which could facilitate differential diagnoses of early-stage SCAs.

Background: and Purpose Spinocerebellar ataxias (SCAs) are the most common form of hereditary ataxias. Extracerebellar signs have been well described and are helpful in differentiating the SCA subtypes. However, there are few reports on the early-stage extracerebellar signs in various SCA subtypes. This study explored the clinical and magnetic resonance imaging (MRI) characteristics of early-stage SCAs in the Korean population. Methods: We retrospectively reviewed the medical records of genetically confirmed SCA patients with a disease duration of <5 years. Data on baseline characteristics, extracerebellar signs, and initial MRI findings were organized based on SCA subtypes. Results: This study included 117 SCA patients with a median age at onset of 40.6 years. The family history was positive in 71.8% of the patients, and the median disease duration and the score on the Scale for the Assessment and Rating of Ataxia at the initial visit were 2.6 years and 5.0, respectively. SCA3 was the most prevalent subtype, and oculomotor abnormalities were the most frequent extracerebellar signs in early-stage SCAs. Saccadic slowing was characteristic of SCA2 and SCA7, and gaze-evoked nystagmus was prominent in SCA6. Parkinsonism was relatively frequent in SCA8 and SCA3. Decreased visual acuity was specific for SCA7. Dementia was not an early manifestation of SCAs. Brain MRI revealed a pattern of pontocerebellar atrophy in SCA2 and SCA7, while SCA6 demonstrated only cerebellar cortical atrophy. Conclusions SCA patients exhibited diverse extracerebellar signs even in the early stage.Specific extracerebellar signs were characteristic of specific subtypes, which could facilitate differential diagnoses of early-stage SCAs.

Although the KMT2B gene was identified as a causative gene for early-onset generalized dystonia, the efficacy of deep brain stimulation (DBS) in KMT2B-related dystonia has not been clearly elucidated. Here, we describe a 28-year-old woman who developed generalized dystonia with developmental delay, microcephaly, short stature, and cognitive decline. She was diagnosed with KMT2B- related dystonia using whole-exome sequencing with a heterozygous frameshift insertion of c.515dupC (p.T172fs) in the KMT2B gene. Oral medications and botulinum toxin injection were not effective. The dystonia markedly improved with bilateral pallidal DBS (the Burke-Fahn-Marsden Dystonia Rating Scale score was reduced from 30 to 5 on the dystonia movement scale and from 11 to 1 on the disability scale), and she could walk independently. From this case, we suggest that bilateral globus pallidus internus DBS can be an effective treatment option for patients with KMT2B-related generalized dystonia.

BACKGROUND: The 5-level triage tool, the Korean Triage and Acuity Scale (KTAS), was developed based on the Canadian Triage and Acuity Scale and has been used for triage in all emergency medical institutions in Korea since 2016. This study evaluated the association between the decrease in level number and the change in its relative importance for disposition in the emergency department (ED). METHODS: Using the registry of the National Emergency Department Information System (NEDIS) ver. 3.1, data regarding consecutive emergency patients from March 2017 to October 2017 were reviewed retrospectively. Reconfiguring KTAS levels, a total of 15 multinomial logistic regression models (KTAS_0 to KTAS_14), including the KTAS, its variants, and covariates were constructed to determine significant factors affecting ED disposition. The relative importance of each model was obtained using a dominance analysis. RESULTS: A total of 79,771 patients were included in the analysis. In the model KTAS_0, the KTAS and 8 covariates were found to be significantly related to ED disposition. The KTAS and the decision maker of each ED visit, whether it was the physician or others, had the largest relative importance, 34.8% and 31.4%, respectively (P < 0.001). In other models of KTAS variants, including 4-level, 3-level and 2-level, the rates of the KTAS decreased to 31.8% (interquartile range [IQR], 28.9–34.2), 26.4% (IQR, 23.2–31.0), and 18.7% (IQR, 7.5–24.9), respectively (P = 0.016). On the other hand, the rates for covariates tended to be larger for smaller triage levels and so there was a significant interaction effect between the KTAS and the covariates according to the triage level (P < 0.001). CONCLUSION: The 5-level triage tool, the KTAS, had the largest relative importance among the predictors affecting ED disposition only at its original level. Therefore, it is recommended that no attempt should be made to reduce the number of levels in the triage tool.
Cohort Studies ; Emergencies ; Emergency Service, Hospital ; Hand ; Humans ; Information Systems ; Korea ; Logistic Models ; Registries ; Retrospective Studies ; Triage

PURPOSE: Glyphosate herbicides (GHs) are widely used and increasingly associated with poisoning cases. Acute pancreatitis (AP) is among the many complications associated with the toxicity of GHs. We investigated the relationship between incidence of AP and its prognosis in patients with GH poisoning. METHODS: This was a retrospective cohort study conducted at a single tertiary hospital between January 2004 and December 2014. We enrolled all patients presented to the emergency department with GH poisoning. The Clinical and laboratory variables were analyzed to investigate the relationship between GH intoxication and AP. RESULTS: We studied 245 patients. Incidence of AP after GH poisoning was 6.5%. Patients with AP (mean 66 years) were older than the non-AP group (56 years). Systolic blood pressure, Glasgow Coma Scale, and amount of ingested poison differed significantly between the two groups. In the blood tests, white blood cell count, alanine aminotransferase, glucose, potassium, amylase, and lipase showed significant differences. The pH, bicarbonate, and lactate levels also differed significantly. Patients with AP demonstrated higher incidence of respiratory failure, pneumonia, acute kidney injury, rhabdomyolysis, and intensive care unit stay time. Additionally, 30-day mortality (n=11, 68.8%) was significantly higher in the AP group. On multivariate analysis, adjusted age, amount of ingestion, and lactate correlated with occurrence of AP. CONCLUSION: The incidence of GH-induced AP was 6.5% with a 30-day mortality of 68.8%. The patient's age, ingested dosage, and lactate levels were associated with GH-induced AP.
Acute Kidney Injury ; Alanine Transaminase ; Amylases ; Blood Pressure ; Cohort Studies ; Eating ; Emergency Service, Hospital ; Glasgow Coma Scale ; Glucose ; Hematologic Tests ; Herbicides ; Humans ; Hydrogen-Ion Concentration ; Incidence ; Intensive Care Units ; Lactic Acid ; Leukocyte Count ; Lipase ; Mortality ; Multivariate Analysis ; Pancreatitis* ; Pneumonia ; Poisoning ; Potassium ; Prognosis* ; Respiratory Insufficiency ; Retrospective Studies ; Rhabdomyolysis ; Tertiary Care Centers

PURPOSE: This study was conducted to examine the efficacies of susceptibility weighted images (SWI) for predicting the clinical prognosis of comatose patients following cardiac arrest. METHODS: Thirty-two patients who were resuscitated from cardiac arrest and underwent brain magnetic resonance imaging (MRI) were retrospectively investigated and compared to 32 subjects with normal brain MRI findings who served as controls. The SWI readings were divided into three categories: prominent, diminished, and normal. Comatose patients were divided into two groups: those with a Glasgow-Pittsburgh cerebral performance category (CPC) of 1-2 (good outcome group) and those with a CPC of 3-5 (poor outcome group). RESULTS: Of the 32 patients, 17 (53.1%) showed good neurological outcomes upon hospital discharge. Normal patterns on SWI were mainly seen in the good outcome group (15 patients, 88.2%), while diminished patterns and prominent patterns were frequently found in the poor outcome group (13 patients, 88.7%). The combination of diminished pattern and prominent pattern predicted poor outcome with 86.7% sensitivity (95% confidence interval, 69.5%-100%) and 88.2% specificity (95% confidence interval, 72.9%-100%). CONCLUSION: The SWI findings correlate with the outcome of hypoxic-ischemic encephalopathy and may be a useful adjunct of vegetative state or death in comatose patients after cardiac arrest.
Brain ; Coma* ; Heart Arrest* ; Humans ; Hypoxia-Ischemia, Brain ; Magnetic Resonance Imaging ; Persistent Vegetative State ; Prognosis ; Reading ; Retrospective Studies ; Sensitivity and Specificity

PURPOSE: Patients suffering from acute poisoning by different substances often visit the emergency department (ED) and receive various prognoses according to the toxic material and patients' condition. Hyperlactatemia, which is an increased blood lactate level that generally indicates tissue hypoperfusion, is commonly utilized as a prognostic marker in critically ill patients such as those with sepsis. This study was conducted to investigate the relationships between blood lactate and clinical prognosis in acute poisoned patients. METHODS: This retrospective study was conducted from January 2013 to June 2014 at a single and regional-tertiary ED. We enrolled study patients who were examined for blood test with lactate among acute intoxicated patients. The toxic materials, patient demographics, laboratory data, and mortalities were also reviewed. Additionally, we analyzed variables including blood lactate to verify the correlation with patient mortality. RESULTS: A total of 531 patients were enrolled, including 24 (4.5%) non-survivors. Patient age, Glasgow coma scale (GCS), serum creatinine (Cr), aspartate transaminase (AST), and serum lactate differed significantly between survivors and non-survivors in the binary logistic regression analysis. Among these variables, GCS, AST, and lactate differed significantly. The median serum lactate levels were 2.0 mmol/L among survivors and 6.9 mmol/L among non-survivors. The AUC with the ROC curve and odds ratio of the initial serum lactate were 0.881 and 3.06 (0.89-8.64), respectively. CONCLUSION: Serum lactate was correlated with fatalities of acute poisoning patients in the ED; therefore, it may be used as a clinical predictor to anticipate their prognoses.
Area Under Curve ; Aspartate Aminotransferases ; Creatinine ; Critical Illness ; Demography ; Emergencies* ; Emergency Service, Hospital* ; Glasgow Coma Scale ; Hematologic Tests ; Humans ; Hyperlactatemia ; Lactic Acid* ; Logistic Models ; Mortality* ; Odds Ratio ; Poisoning ; Prognosis ; Retrospective Studies ; ROC Curve ; Sepsis ; Survivors

PURPOSE: Flumazenil is an effective benzodiazepine antagonist. However, serious adverse effects, including seizures, cardiac arrhythmias, and even death, have been reported in patients treated with flumazenil. These adverse effects are commonly associated with co-ingested tricyclic antidepressants and benzodiazepine withdrawal. Herein, we examined the safety, effectiveness, and risk of using flumazenil to treat suspected benzodiazepine overdose in the emergency department (ED). METHODS: This is a retrospective observational study of adult patients administered with flumazenil for a known or suspected benzodiazepine overdose in the ED between July 2010 and January 2016. The outcomes included mental status improvement, incidence of seizures, and intubation rate after flumazenil administration. RESULTS: Seventy-six patients were included in the analysis. Thirty-eight (50%) patients experienced clinically significant mental status improvement. One patient had a seizure (1.3%), despite 17 reported proconvulsant coingestants. No patient required endotracheal intubation, and no patient had arrhythmias after flumazenil administration. Flumazenil was given intravenously bolus in all cases, and the average dose was 0.44mg. There were no significant changes in the vital signs after flumazenil administration. CONCLUSION: Flumazenil was effective and associated with a low frequency of seizure. However, patients with contraindications may develop seizures. The benefits with respect to risk of adverse effects should be considered carefully in all patients.
Adult ; Antidepressive Agents, Tricyclic ; Arrhythmias, Cardiac ; Benzodiazepines* ; Drug Overdose ; Emergencies* ; Emergency Service, Hospital* ; Flumazenil* ; Humans ; Incidence ; Intubation ; Intubation, Intratracheal ; Observational Study ; Retrospective Studies ; Seizures ; Vital Signs

The change of compressing personnel will inevitably accompany hands off time when cardiopulmonary resuscitation (CPR) is performed by two or more rescuers. The present study assessed whether changing compression by a second rescuer located on the opposite side (OS) of the first rescuer can reduce hands-off time compared to CPR on the same side (SS) when CPR is performed by two rescuers. The scenario of this randomized, controlled, parallel simulation study was compression-only CPR by two laypersons in a pre-hospital situation. Considering sex ratio, 64 participants were matched up in 32 teams equally divided into two gender groups, i.e. , homogenous or heterogeneous. Each team was finally allocated to one of two study groups according to the position of changing compression (SS or OS). Every team performed chest compression for 8 min and 10 sec, with chest compression changed every 2 min. The primary endpoint was cumulative hands-off time. Cumulative hands-off time of the SS group was about 2 sec longer than the OS group, and was significant (6.6 +/- 2.6 sec vs. 4.5 +/- 1.5 sec, P = 0.005). The range of hands off time of the SS group was wider than for the OS group. The mean hands-off times of each rescuer turn significantly shortened with increasing number of turns (P = 0.005). A subgroup analysis in which cumulative hands-off time was divided into three subgroups in 5-sec intervals revealed that about 70% of the SS group was included in subgroups with delayed hands-off time > or = 5 sec, with only 25% of the OS group included in these subgroups (P = 0.033). Changing compression at the OS of each rescuer reduced hands-off time compared to the SS in prehospital hands-only CPR provided by two bystanders.
Cardiopulmonary Resuscitation/methods/*statistics & numerical data ; Clinical Competence/*statistics & numerical data ; Emergency Medical Services/*statistics & numerical data ; Female ; Heart Arrest/epidemiology/*prevention & control ; Heart Massage/methods/*statistics & numerical data ; Humans ; Male ; Republic of Korea/epidemiology ; Treatment Outcome ; Workload/*statistics & numerical data ; Young Adult