Acute kidney injury as a prognostic predictor of in-hospital mortality and neurological outcomes in patients after extracorporeal cardiopulmonary resuscitation.

INTRODUCTION: Extracorporeal cardiopulmonary resuscitation (ECPR) is increasingly being applied to patients with refractory cardiac arrest, but the survival rate to hospital discharge is only approximately 29%. Because ECPR requires intensive resources, it is important to predict outcomes. We therefore investigated the prognostic association between acute kidney injury (AKI) and ECPR to confirm the performance of AKI as a prognostic predictor of in-hospital mortality and neurological outcomes in ECPR. METHODS: We conducted a retrospective observational study on patients undergoing ECPR for cardiac etiology at Chonnam National University Hospital from 2015 to 2021. The group diagnosed with AKI in any KDIGO category within the first 48 h after ECPR was compared to that without AKI, and the primary outcome of the study was in-hospital mortality. RESULTS: Of 138 enrolled patients, 83 were studied. Hospital mortality occurred in 49 patients (59%), and 55 (66.3%) showed poor neurological outcomes. The AKI group displayed significantly elevated in-hospital mortality (77.8% vs 24.1%) and poor neurological outcomes (81.5% vs 37.9%) compared to the non-AKI group (p < 0.001). Regression analysis showed that AKI was associated with significantly higher rates of both in-hospital mortality (odds ratio (OR) range 10.75-12.88) and neurologic outcomes (OR range 5.9-6.22). CONCLUSIONS: There was a significant association of AKI with both in-hospital mortality and poor neurologic outcome in patients after ECPR, and AKI can be used as an early prognostic predictor in these patients.

Prognostic value of neutrophil to lymphocyte ratio in the diagnosis of neurotoxicity after glufosinate ammonium poisoning.

Neurotoxicity related to glufosinate ammonium is known to occur after a latent period of 4-60 hr following ingestion of this herbicide. However, neurotoxicity is difficult to predict in the emergency department (ED) and only a few parameters are known to be useful to indicate development of neurotoxicity. Determination of a systemic inflammation parameter such as the neutrophil to lymphocyte ratio (NLR), is a rapid and simple method which was found to be a prognostic marker in various clinical conditions such as sepsis, cardiac disorders, stroke, and cancer. Therefore, the aim of this study was to determine whether the NLR might predict neurotoxicity and be used at ED to detect neurotoxicity induced following glufosinate ammonium poisoning in admitted patients. This retrospective observational study collected data from consecutive patients diagnosed with acute glufosinate ammonium poisoning between January 2005 and December 2020. The primary outcome was development of neurotoxicity following acute glufosinate ammonium poisoning. Out of the 72 patients selected 44 patients (61.1%) exhibited neurotoxic symptoms. Neurotoxicity appeared with an approximate latent period of 12 hr. The NLR was significantly higher in the group displaying neurotoxicity. Multivariable analysis showed that the NLR was significant in predicting neurotoxicity. The NLR was independently associated with neurotoxicity initiated by glufosinate ammonium. Therefore, the use of the NLR might help clinically to readily and rapidly predict development of neurotoxicity associated with glufosinate ammonium at the ED.

Diagnostic value of transthoracic echocardiography compared to electrocardiogram in predicting coronary artery stenosis among patients after cardiac arrest.

BACKGROUND: In the absence of ST-segment elevation (STE) in post-return of spontaneous circulation (ROSC) electrocardiogram (ECG), coronary angiography (CAG) is required in patients with suspected coronary artery disease (CAD). However, it is a challenge to identify patients with CAD after cardiac arrest (CA). Recent European Society of Cardiology guidelines recommends transthoracic echocardiography in patients presenting with cardiac arrest. We aimed to assess the diagnostic value of regional wall motion abnormalities (RWMAs) on transthoracic echocardiography (TTE) compared to ECG in diagnosing significant coronary artery stenosis in CA patients. METHODS: This is a retrospective, observational study of adult CA patients with presumed cardiac etiology who underwent CAG from a single tertiary care hospital. We compared the predictive value of RWMA on TTE and STE on ECG in significant stenosis of ≥70% of the coronary artery diameter. The primary outcome was significant stenosis on CAG. RESULTS: There were 145 patients included in this study and CAG revealed significant stenosis in 76 (52.4%) patients. Among the 76 patients with significant stenosis, 68 (89.5%) had RWMA on TTE and 41 (54.0%) had STE. RWMA on TTE (OR 3.67; 95% CI 1.52-8.85) was independently associated with significant stenosis. Combining both RWMA on TTE and STE on ECG improved performance in the receiver operating characteristic curve analysis (area under the curve 0.722) for predicting significant stenosis compared to using only ECG alone (p = 0.001). CONCLUSIONS: RWMAs on TTE was independently associated with significant stenosis. The RWMA and STE combination had better predictive performance than using only STE on ECG to predict significant stenosis.

Quantitative analysis of aconitine in body fluids in a case of aconitine poisoning.

Aconitine belongs to the Aconitum alkaloids and is a natural toxic substance. Aconitine has been used as a traditional medicine in East Asian culture. Today, aconitine is still in use with or without a prescription, in the Republic of Korea. Here we present a case report of accidental death due to acute aconitine poisoning. An 81-year-old woman ingested liquid that had been heat extracted from the root of the Aconitum plant; she presented to the emergency room 1 h after ingestion. Her electrocardiogram showed irregular ventricular arrhythmias including ventricular tachycardia; she progressed to cardiac arrest. Cardiopulmonary resuscitation and anti-arrhythmic drugs were administered, but the patient did not survive. An autopsy was performed 2 days postmortem. Toxicological analysis was performed, and aconitine was detected by liquid chromatography tandem mass spectrometry. The antemortem blood concentration of aconitine was 39.1 ng/ml and the concentrations of aconitine in the postmortem cardiac blood, peripheral blood, cerebrospinal fluid (CSF), pericardial fluid, and urine were 21.1 ng/ml, 28.6 ng/ml, 6.8 ng/ml, 24.1 ng/ml, and 67.4 ng/ml, respectively. This is the first forensic case report of an aconitine poisoning death in the Republic of Korea with quantitative measurement of aconitine in the antemortem blood and various postmortem body fluids. To the best of our knowledge, this is the first report of the detection of aconitine in the CSF. These data about the distribution of aconitine in the antemortem blood and various postmortem body fluids is helpful for future aconitine poisoning death cases.

Successful extracorporeal life support in respiratory failure after copper sulphate ingestion.

A 44-year-old woman intentionally ingested a solution of copper sulphate. She had minimal intravascular haemolysis and methemoglobinaemia but developed acute respiratory distress syndrome (ARDS) 4 hours after acute copper sulphate poisoning. This required extracorporeal membrane oxygenation (ECMO) management in the intensive care unit. Subsequently, she improved clinically and was successfully weaned from ECMO. Acute copper sulphate poisoning can cause severe pulmonary toxicity even in the absence of other serious symptoms. Therefore, a physician treating acute copper sulphate poisoning should look out for respiratory symptoms even in the absence of other common symptoms. We suggest early initiation of venovenous ECMO in those with ARDS following copper sulphate poisoning.

The characteristics of emergency department presentations related to acute herbicide or insecticide poisoning in South Korea between 2011 and 2014.

The aim of this study was to examine epidemiologic data regarding acute herbicide or insecticide poisoning in adults from 2011 to 2014 at the national level in South Korea. Further, the association between governmental regulations involving pesticides and changes in pesticide poisoning occurrences over time was determined. Data were obtained from the emergency department (ED)-based Injury In-depth Surveillance system conducted by the Korea Center for Disease Control and Prevention (KCDC). Governmental regulations on pesticides were downloaded from the homepage of the Korea Rural Development Administration. Pesticides were classified according to guidelines provided by the World Health Organization (WHO) and by the respective Resistance Action Committee (RAC). Trends in the number of ED presentations and case fatality rate (CFR) due to pesticide poisoning were investigated. The overall CFR due to poisoning from herbicides or insecticides in adults in South Korea was 16.8% during 2011-2014. However, CFR significantly decreased over the 4-year period. The ED presentations of paraquat (PQ) poisoning fell significantly, whereas poisoning due to glyphosate, glufosinate, or combined herbicides increased markedly over the 4 years. Between 2011 and 2013, PQ was the most common pesticide poisoning, whereas glyphosate became the most frequent in 2014. PQ produced the highest rate of fatality followed by endosulfan. Although the frequency of PQ poisoning decreased, which may be attributed to governmental regulations, the CFR and incidence of pesticide poisoning in adults remain a public health concern that needs to be addressed.

Severe Coagulopathy after Ingestion of "Snake Wine".

BACKGROUND: This report describes a patient who developed coagulopathy after ingesting snake wine, which is an alcoholic libation containing an entire venomous snake. CASE REPORT: A 68-year-old man was admitted to the hospital 19 h after ingesting snake wine. The laboratory features upon admission included unmeasurable activated partial thromboplastin (aPTT) values, prolonged prothrombin time (PT) values, increased fibrinogen levels, modestly elevated fibrin degradation product and D-dimer values, uncorrected aPTT and PT values after a mixing test, and normal levels of aspartate transaminase and alanine transaminase. No pesticides, warfarin, or superwarfarin in the patient's blood or urine were detected. His coagulation profile normalized on the 6(th) day after admission after antivenom treatment. He was discharged 10 days later without sequelae. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: The physician should be aware that ingesting snake wine may lead to systemic envenomation. As for coagulopathy, which may develop by ingesting snake venom, related laboratory findings may differ from the features observed after direct envenomation by snakebite.

An electroactive biotin-doped polypyrrole substrate that immobilizes and releases EpCAM-positive cancer cells.

The specific capture and remotely controlled release of the EpCAM-positive cancer cells from biotin-doped polypyrrole (Ppy) films in response to an electrical potential is presented. As Ppy allows the direct incorporation of biotin molecules during the electrochemical process, densely packed biotin molecules can serve as the binding sites for streptavidin-tagged biomolecular complexes. This study demonstrates not only the enhanced capture and enrichment of EpCAM-positive cancer cells but also "on-demand" release of the viable cells from conductive Ppy in an electrical-potential-dependent way. This novel approach is of great importance in a diverse range of applications, and in particular in cancer diagnostics and screening.

The association between the neutrophil lymphocyte ratio and local edema after viper snake envenomation in South Korea.

The role of the inflammatory process in the pathogenesis of local edema-related envenomation has not been explored with endemic venomous snakebites in Korea. Gloydius species are responsible for most snakebites in South Korea. In this study we aimed to investigate whether the neutrophil-lymphocyte ratio is relevant to snake envenomation-induced local edema in South Korea. This retrospective study divided 126 patients into two groups according to local edema severity at presentation. Logistic regression models were used to investigate the association between the neutrophil-lymphocyte ratio and local edema. Sixty-one (48.4%) patients had grade 2 or higher local edema at presentation despite 21 of them being given antivenom before presentation. During hospitalization, local edema progressed in 61 patients 48 (11.5-48) hours after presentation, and 54 patients demonstrated grade 3 or higher local edema. A higher neutrophil-lymphocyte ratio at presentation after adjustment for factors related to envenomation and antivenom administration and factors influencing the neutrophil-lymphocyte ratio were associated with both a higher grade of local edema at presentation and a higher peak local edema grade during hospitalization. The delta neutrophil-lymphocyte ratio during the first 24 h after presentation was related to the local edema progression after presentation. The neutrophil-lymphocyte ratio at presentation is associated with the severity of local edema-related envenomation. Furthermore, the change in the neutrophil-lymphocyte ratio during the first 24 h is related to the risk of local edema progression. Further clinical and experimental research aimed at investigating the role of inflammation on the pathogenesis of local edema should be conducted. This study may suggest the introduction of short-term anti-inflammatory agents considering the failure of antivenom to curb local edema.

Clinical features of snake envenomation in South Korea.

INTRODUCTION: Three venomous snakes of the Gloydius genus belonging to the Viperidae family cause most snake envenomations in South Korea. Envenomation signs often include local swelling, coagulopathy, and rhabdomyolysis. The benefit of additional antivenom after the initial does is unclear. METHODS: This retrospective study divided patients into four groups according to the presence of rhabdomyolysis (creatine kinase ≥1000 IU/L) and coagulopathy, which were defined using the Korean Society on Thrombosis and Hemostasis disseminated intravascular coagulation score (rhabdomyolysis, coagulopathy, combination, and local effects groups). We describe the clinical features of envenomation and the antivenom response. RESULTS: Greater local swelling predicted more severe snakebite pain. Ninety of the 231 enrolled patients (38.9%) developed rhabdomyolysis. The patients with severe rhabdomyolysis in the combination group displayed higher peak creatine kinase activity than the rhabdomyolysis group. Seven patients with rhabdomyolysis, including two patients requiring kidney replacement therapy, developed acute kidney injury, but the incidence of acute kidney injury did not differ between the combination group and rhabdomyolysis group. Bleeding developed in 3.5% of the patients, but its incidence did not differ between the combination and coagulopathy groups. Approximately half of all patients needed repeated antivenom administration, mainly due to the local envenomation effect. Earlier administration of additional antivenom for progressive local swelling did not reduce the hospitalization duration. CONCLUSION: Rhabdomyolysis is one of the major effects of Gloydius snake envenomation in South Korea, although it is not associated with the same risk of clinical deterioration as coagulopathy. Additionally, the ability of antivenom to ameliorate local swelling should be investigated to prevent unnecessary antivenom administration in South Korea.

The trend of ammonia levels in patients with glufosinate ammonium poisoning with respect to neurotoxicity.

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

High incidence of acute kidney injury in extracorporeal resuscitation, Leading to poor prognosis.

Background: Extracorporeal membrane oxygenation (ECMO) patients have a high incidence of acute kidney injury (AKI). Extracorporeal cardiopulmonary resuscitation (ECPR) patients are more likely to develop AKI than ECMO patients because of serious injury during cardiac arrest (CA). Objectives: This study aims to assess the occurrence and outcomes of AKI in ECPR and ECMO, and to identify specific risk factors and clinical implications of AKI in ECPR. Methods: This is a retrospective observational study from a single tertiary care hospital in Gwangju, Korea. Adults (≥18 years) who received ECMO with cardiac etiology in the emergency and inpatient departments from January 2015 to December 2021 were included. The patients (n = 169) were divided into two groups, ECPR and ECMO without CA, and the occurrence of AKI was investigated. The primary outcome of the study was in-hospital mortality, and the secondary outcomes were six-month cerebral performance category (CPC) and AKI during hospitalization. Results: The incidence of AKI was significantly higher with ECPR (67.5 %) than with ECMO without CA (38.4 %). ECPR was statistically significant for Expire (adjusted OR (aOR) 2.45, 95 % CI 1.28-4.66) and Poor CPC (2.59, 1.32-5.09). AKI was also statistically significant for Expire (6.69, 3.37-13.29) and Poor CPC (5.45, 2.73-10.88). AKI was the determining factor for the outcomes of ECPR (p = 0.01). Conclusions: ECPR patients are more likely to develop AKI than ECMO without CA patients. In ECPR patients, AKI leads to poor outcomes. Therefore, clinicians should be careful not to develop AKI in ECPR patients.

A new idea for simple and rapid monitoring of gene expression: requirement of nucleotide sequences encoding an N-terminal HA tag in the T7 promoter-driven expression in E. coli.

Mammalian expression vectors are used to overexpress genes of interest in mammalian cells. High temperature requirement protein A1 (HtrA1), used as a specific target, was expressed from the pHA-M-HtrA1 plasmid in HEK293T cells, inducing cell death. Expression of HtrA1 was driven by the pHA-M-HtrA1 mammalian expression vector in E. coli resulting in growth suppression of E. coli in an HtrA1 serine protease-dependent manner. By using various combinations of promoters, target genes and N-terminal tags, the T7 promoter and N-terminal HA tag in the mammalian expression vector were shown to be responsible for expression of target genes in E. coli. Thus the pHA-M-HtrA1 plasmid can be used as a novel, rapid pre-test system for expression and cytotoxicity of the specific target gene in E. coli before assessing its functions in mammalian cells.

The novel human HtrA2 ortholog in zebrafish: New molecular insight and challenges into the imbalance of homeostasis.

High temperature requirement A2 (HtrA2) contributes to regulating mitochondrial quality control and maintaining the balance between the death and survival of cells and living organisms. However, the molecular mechanism of HtrA2 in physiological and pathophysiological processes remains unclear. HtrA2 exhibits multifaceted characteristics according to the expression levels and acts opposite functions depending on its subcellular localization. Thus, innovative technologies and systems that can be freely manipulated at the quantitative, biochemical, molecular and cellular levels are needed to address not only the challenges faced by HtrA2 research but also the general obstacles to protein research. Here, we are the first to identify zebrafish HtrA2 (zHtrA2) as the true ortholog of human HtrA2 (hHtrA2), by in silico sequence analysis of genomic DNA and molecular biological techniques, which is highly conserved structurally and functionally as a serine protease and cell death regulator. The zHtrA2 protein is primarily localized in the mitochondria, where alanine-exposed mature zHtrA2 ((A)-zHtrA2) is generated by removing 111 residues at the N-terminus of pro-zHtrA2. The (A)-zHtrA2 released from the mitochondria into the cytosol induces the caspase cascade by binding to and inhibiting hXIAP, a cognate partner of hHtrA2. Notably, zHtrA2 has well conserved properties of serine protease that specifically cleaves hParkin, a cognate substrate of hHtrA2. Interestingly, cytosolic (M)-zHtrA2, which does not bind hXIAP, induces atypical cell death in a serine protease-dependent manner, as occurs in hHtrA2. Thus, the zebrafish-zHtrA2 system can be used to clarify the crucial role of HtrA2 in maintaining the survival of living organisms and provide an opportunity to develop novel therapeutics for HtrA2-associated diseases, such as neurodegenerative diseases and cancer, which are caused by dysregulation of HtrA2.

The sCMV IE enhancer/promoter system for high-level expression and efficient functional studies of target genes in mammalian cells and zebrafish.

Human and simian cytomegalovirus immediate-early (IE) enhancer/promoter (hCMVp and sCMVp) are the most widely used system for high-level gene expression; however, studies on detailed comparative analyses of the promoters are scarce. Using GFP reporter gene and immunoblotting assays, we have shown that the transcriptional activity of sCMVp was two to four fold higher than those of hCMVp in human-, monkey-, mouse-originated cell lines, and zebrafish as a vertebrate animal model. Notably, HtrA1 driven by the sCMVp induced cell death at relatively high-levels in HEK293 cells, but HtrA1 driven by the hCMVp had almost no effect on cell death, as shown by more than 4-fold increase in the expression levels of HtrA1. Our data may provide a valuable tool for functional studies of target genes that are expressed at extreme low level under standard transfection conditions and for development of new gene therapeutic systems.

Fentanyl intoxication caused by abuse of transdermal fentanyl.

Fentanyl has an analgesic effect 100 times greater than that of morphine; therefore, transdermal administration of fentanyl has been widely used to control pain. Due to misconceptions regarding the proper use of fentanyl, its simple method of administration, and the absence of regulatory rules regarding its use, both medical providers and non-medical providers have abused fentanyl. We report on three cases of fentanyl intoxication and suggest solutions to prevent its abuse in the future. Three patients were intoxicated by transdermal fentanyl, which resulted in respiratory depression. Two of these cases were attributed to non-medical use of the drug and the other occurred while using fentanyl as directed by medical personnel. Physicians should use transdermal fentanyl only to control chronic pain, and rules should be established to prevent abuse of fentanyl that occurs due to its ease of use and the absence of any established policy regarding the prescription and disposal of this drug.

The clinical role of serum albumin in Organophospate poisoning.

This retrospective study investigated whether the serum albumin (SA) concentration at presentation is associated with mortality and the mechanism underlying the association. This study enrolled 217 patients poisoned with organophosphate (OP). Hypoalbuminemia (albumin <3.5 g/dL) at presentation was identified in 18.4% of the patients poisoned with OP. The hypoalbuminemia group experienced a more complicated clinical course and had a higher mortality rate than the normoalbuminemia and hyperalbuminemia groups. The SA concentration correlated with the CRP level at presentation but not with the body mass index in patients with OP poisoning. Furthermore, the change in the SA concentration during the first 24 hours also correlated with the change in BuChE activity in patients with fenitrothion poisoning. The SA concentration at presentation was independently associated with mortality after adjusting for inflammation and nutritional status. This study showed that the SA concentration at presentation is associated with the mortality risk of patients poisoned with OP. This association is independent of inflammation and nutritional status in OP poisoning, and in particular, the protective effect of SA might contribute to this association in fenitrothion poisoning. These results should be validated.

Is two-dimensional echocardiography better than electrocardiography for predicting patient outcomes after cardiac arrest?

BACKGROUND: Coronary artery stenosis increases hospital mortality and leads to poor neurological recovery in cardiac arrest (CA) patients. However, electrocardiography (ECG) cannot fully predict the presence of coronary artery stenosis in CA patients. Hence, we aimed to determine whether regional wall motion abnormality (RWMA), as observed by two-dimensional echocardiography (2DE), predicted patient survival outcomes with greater accuracy than did ST segment elevation (STE) on ECG in CA patients who underwent coronary angiography (CAG) after return of spontaneous circulation. METHODS: This was a retrospective observational study of adult patients with CA of presumed cardiac etiology who underwent CAG at a single tertiary care hospital. We investigated whether RWMA observed on 2DE predicted patient outcomes more accurately than did STE observed on ECG. The primary outcome was incidence of hospital mortality. The secondary outcomes were Glasgow-Pittsburgh Cerebral Performance Category scores measured 6 months after discharge and significant coronary artery stenosis on CAG. RESULTS: Among the 145 patients, 36 (24.8%) experienced in-hospital death. In multivariable analysis of survival outcomes, only total arrest time (P=0.011) and STE (P=0.035) were significant. The odds ratio (OR) and 95% confidence interval (CI), which were obtained by adjusting the total arrest time for survival outcomes, were significant only for STE (OR, 0.40; 95% CI, 0.17-0.94). The presence of RWMA was not a significant factor. CONCLUSIONS: While STE predicted survival outcomes in adult CA patients, RWMA did not. The decision to perform CAG after CA should include ECG under existing guidelines. The use of RWMA has limited benefits in treatment of this population.

Reversible posterior leukoencephalopathy syndrome.

Reversible posterior leukoencephalopathy syndrome (RPLS) is a neurological disorder characterized by signs of posterior cerebral edema upon radiographic examination. RPLS has been strongly associated with abrupt and significant elevations in blood pressure or the administration of immunosuppressive drugs. Here, we report a case of RPLS occurring in a 30-year-old-mother with a presumed amniotic fluid embolism subsequent to delivery by cesarean section. On the fifth day after the initial successful resuscitation from the cardiorespiratory collapse, she manifested generalized seizure activity and abnormal radiological findings, which were found to be consistent with RPLS. Through our experience, we have suggested that RPLS might occur more easily at lower blood pressures than has been previously recognized. It is important to consider the lower limit at which blood pressure is controlled, especially if accompanied with fever.