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The Panbio COVID-19/Flu A&B Panel (Abbott) is an in vitro diagnostic rapid test designed for the qualitative detection of nucleocapsid proteins SARS-CoV-2 and nucleoprotein influenza A and B antigens in nasal mid-turbinate (NMT) swab specimens from symptomatic individuals meeting COVID-19 and influenza clinical and/or epidemiological criteria. This study, the largest global one to date using fresh samples, aimed to assess the diagnostic sensitivity and specificity of the Panbio COVID-19/Flu A&B Panel in freshly collected NMT swab specimens from individuals suspected of respiratory viral infection consistent with COVID-19 and/or influenza within the first 5 days of symptom onset compared with results obtained with the cobas SARS-CoV-2 and influenza A/B qualitative assay (cobas 6800/8800 systems), which were tested using nasopharyngeal swab samples. A total of 512 evaluable subjects were enrolled in the COVID-19 cohort across 18 sites, and 1,148 evaluable subjects were enrolled in the influenza cohort across 22 sites in the Asia-Pacific, Europe, and the USA. The Panbio COVID-19/Flu A&B Panel demonstrated a sensitivity of 80.4% and a specificity of 99.7% for COVID-19. For influenza A, the sensitivity and specificity rates were 80.6% and 99.3%, respectively. Likewise, for influenza B, the sensitivity and specificity rates were 80.8% and 99.4%, respectively. In conclusion, the Panbio COVID-19/Flu A&B Panel emerges as a suitable rapid test for detecting COVID-19 and influenza in symptomatic subjects across diverse global populations, exhibiting high sensitivity. The assay achieved a sensitivity of 94.4% in samples with Ct ≤24 for COVID-19 and 92.6% in samples with Ct ≤30 for influenza A and B. IMPORTANCE: The Panbio COVID-19/Flu A&B Panel is a suitable rapid test for detecting COVID-19 and influenza in symptomatic subjects across diverse global populations, exhibiting high sensitivity. The assay achieved a sensitivity of 94.0% in samples with Ct ≤24 for COVID-19 and 92.6% in samples with Ct ≤30 for influenza A and B.
Subject(s)
Antigens, Viral , COVID-19 , Influenza A virus , Influenza B virus , Influenza, Human , SARS-CoV-2 , Sensitivity and Specificity , Humans , COVID-19/diagnosis , Influenza, Human/diagnosis , Influenza, Human/virology , Influenza B virus/isolation & purification , Influenza B virus/immunology , SARS-CoV-2/immunology , SARS-CoV-2/isolation & purification , Adult , Middle Aged , Female , Male , Antigens, Viral/analysis , Antigens, Viral/immunology , Young Adult , Adolescent , Aged , Influenza A virus/isolation & purification , Influenza A virus/immunology , Child , Child, Preschool , Nasopharynx/virology , COVID-19 Testing/methods , Infant , Aged, 80 and overABSTRACT
Extracorporeal cardiopulmonary resuscitation (ECPR) is increasingly performed as an adjunct to conventional cardiopulmonary resuscitation (CCPR) for refractory out-of-hospital cardiac arrest (OHCA). However, the specific benefits of ECPR concerning survival with favorable neurological outcomes remain uncertain. This study aimed to investigate the potential advantages of ECPR in the management of refractory OHCA. We conducted a retrospective cohort study involved OHCA patients between January 2016 and May 2021. Patients were categorized into ECPR or CCPR groups. The primary endpoint assessed was survival with favorable neurological outcomes, and the secondary outcome was survival rate. Multivariate logistic regression analyses, with and without 1:2 propensity score matching, were employed to assess ECPR's effect. In total, 1193 patients were included: 85underwent ECPR, and 1108 received CCPR. Compared to the CCPR group, the ECPR group exhibited notably higher survival rate (29.4% vs. 2.4%; p < 0.001). The ECPR group also exhibited a higher proportion of survival with favorable neurological outcome than CCPR group (17.6% vs. 0.7%; p < 0.001). Multivariate logistic regression analysis demonstrated that ECPR correlated with increased odds of survival with favorable neurological outcome (adjusted odds ratio: 13.57; 95% confidence interval (CI) 4.60-40.06). Following propensity score matching, the ECPR group showed significantly elevated odds of survival with favorable neurological outcomes (adjusted odds ratio: 13.31; 95% CI 1.61-109.9). This study demonstrated that in comparison to CCPR, ECPR may provide survival benefit and increase the odds of favorable neurological outcomes in selected OHCA patients.
Subject(s)
Cardiopulmonary Resuscitation , Extracorporeal Membrane Oxygenation , Out-of-Hospital Cardiac Arrest , Propensity Score , Humans , Out-of-Hospital Cardiac Arrest/therapy , Out-of-Hospital Cardiac Arrest/mortality , Male , Female , Middle Aged , Cardiopulmonary Resuscitation/methods , Extracorporeal Membrane Oxygenation/methods , Retrospective Studies , Aged , Treatment Outcome , Survival RateABSTRACT
Despite the exact biological role of HNF1 homolog A (HNF1A) in the regulatory mechanism of glioblastoma (GBM), the molecular mechanism, especially the downstream regulation as a transcription factor, remains to be further elucidated. Immunohistochemistry was used to detect the expression and clinical relevance of HNF1A in GBM patients. CCK8, TUNEL, and subcutaneous tumor formation in nude mice were used to evaluate the effect of HNF1A on GBM in vitro and in vivo. The correction between HNF1A and epidermal growth factor receptor pathway substrate 8 (EPS8) was illustrated by bioinformatics analysis and luciferase assay. Further mechanism was explored that the transcription factor HNF1A regulated the expression of EPS8 and downstream signaling pathways by directly binding to the promoter region of EPS8. Our comprehensive analysis of clinical samples in this study showed that upregulated expression of HNF1A was associated with poor survival in GBM patients. Further, we found that knockdown of HNF1A markedly suppressed the malignant phenotype of GBM cells in vivo and in vitro as well as promoted apoptosis of tumor cells, which was reversed by upregulation of HNF1A. Mechanistically, HNF1A could significantly activate PI3K/AKT signaling pathway by specifically binding to the promoter regions of EPS8. Moreover, overexpression of EPS8 was able to reverse the apoptosis of tumor cells caused by HNF1A knockdown, thereby exacerbating the GBM progression. Correctively, our study has clarified the explicit mechanism by which HNF1A promotes GBM malignancy and provides a new therapeutic target for further clinical application.
Subject(s)
Glioblastoma , Proto-Oncogene Proteins c-akt , Animals , Mice , Humans , Proto-Oncogene Proteins c-akt/genetics , Proto-Oncogene Proteins c-akt/metabolism , Phosphatidylinositol 3-Kinases/genetics , Phosphatidylinositol 3-Kinases/metabolism , Glioblastoma/genetics , Glioblastoma/pathology , Mice, Nude , Cell Proliferation , Cell Line, Tumor , Signal Transduction , Transcription Factors/metabolism , Gene Expression Regulation, Neoplastic , Hepatocyte Nuclear Factor 1-alpha/genetics , Hepatocyte Nuclear Factor 1-alpha/metabolism , Adaptor Proteins, Signal Transducing/metabolismABSTRACT
BACKGROUND: Dual antiplatelet therapy (DAPT) is a standard treatment option for acute myocardial infarction (AMI). The difference between the efficacy of ticagrelor and clopidogrel in the emergency department (ED) before percutaneous coronary intervention (PCI) remains unknown. The present study compared the in-hospital major adverse cardiovascular event (MACE) rates between patients with AMI treated with clopidogrel and those treated with ticagrelor in the ED before PCI. METHODS: We retrospectively collected the data of patients diagnosed as having AMI in the ED. Patients were only included if they had successfully received complete DAPT with aspirin and ticagrelor/clopidogrel in the ED and had undergone PCI. The patients were divided into two groups according to their DAPT regimen. The primary outcome was the rate of in-hospital MACEs. The secondary outcomes included an unexpected return to the ED within 72 h, readmission within 14 d, and revascularization. RESULTS: A total of 1836 patients were enrolled. Patients in the ticagrelor group had a lower in-hospital MACE rate (3.01% versus 7.51%, p < 0.001) and in-hospital mortality rate (2.15% versus 5.70%, p < 0.001) than those in the clopidogrel group. Multivariate logistic regression analysis revealed ticagrelor was independently associated with a lower risk of in-hospital MACEs (odds ratio [OR]: 0.53, 95% CI: 0.32-0.88, p = 0.013). After propensity score matching, the risk of in-hospital MACEs remained significantly lower in the ticagrelor group (OR 0.42, 95% CI: 0.21-0.85, p = 0.016). CONCLUSION: DAPT with ticagrelor and aspirin in the ED before PCI is associated with a lower in-hospital MACE rate among patients with AMI.
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Over the past few decades, mechanisms of programmed cell death have attracted the scientific community because they are involved in diverse human diseases. Initially, apoptosis was considered as a crucial mechanistic pathway for programmed cell death; recently, an alternative regulated mode of cell death was identified, mimicking the features of both apoptosis and necrosis. Several lines of evidence have revealed that dysregulation of necroptosis leads to pathological diseases such as cancer, cardiovascular, lung, renal, hepatic, neurodegenerative, and inflammatory diseases. Regulated forms of necrosis are executed by death receptor ligands through the activation of receptor-interacting protein kinase (RIPK)-1/3 and mixed-lineage kinase domain-like (MLKL), resulting in the formation of a necrosome complex. Many papers based on genetic and pharmacological studies have shown that RIPKs and MLKL are the key regulatory effectors during the progression of multiple pathological diseases. This review focused on illuminating the mechanisms underlying necroptosis, the functions of necroptosis-associated proteins, and their influences on disease progression. We also discuss numerous natural and chemical compounds and novel targeted therapies that elicit beneficial roles of necroptotic cell death in malignant cells to bypass apoptosis and drug resistance and to provide suggestions for further research in this field.
Subject(s)
Necroptosis , Receptor-Interacting Protein Serine-Threonine Kinases , Humans , Receptor-Interacting Protein Serine-Threonine Kinases/metabolism , Protein Kinases/metabolism , Necrosis/metabolism , Cell Death , Apoptosis/physiologyABSTRACT
BACKGROUND: Sudden cardiac arrest (SCA) is a critical complication of acute myocardial infarction, especially ST-segment elevation myocardial infarction (STEMI). This study identified the risk factors for SCA in patients with STEMI before receiving catheterization. METHODS: We retrospectively analyzed the data of patients with STEMI and cardiac arrest who presented to a tertiary care center in Taiwan between January 1, 2016, and December 31, 2019. Only patients with coronary artery disease (CAD) confirmed by coronary angiography were included in this study. We collected the patients' demographic and clinical data, such as age, sex, medical history, estimated glomerular filtration rate (eGFR), and coronary angiographic findings. The primary outcome of this study was SCA in patients with STEMI. Continuous and nominal variables were compared using the two-sample Student's t-test and chi-squared test, respectively. The results of logistic regression were subjected to multivariate analysis with adjustment for possible confounders. RESULTS: A total of 920 patients with STEMI and coronary angiography-documented CAD and 108 patients with SCA who presented between January 1, 2016, and December 31, 2019, were included. The bivariate logistic regression analysis of patients' demographic data revealed that patients with STEMI and SCA were slightly younger, were more likely to have diabetes mellitus, and had a lower eGFR than did the patients without SCA. The coronary angiographic findings indicated a higher prevalence of left main CAD and three-vessel disease in patients with SCA than in patients without SCA. Multivariate logistic regression revealed that left main CAD (odds ratio [OR]: 3.77; 95% confidence interval [CI], 1.84 to 7.72), a lower eGFR (OR: 0.97; 95% CI, 0.96 to 0.98), and younger age (OR: 0.98; 95% CI, 0.96 to 0.99) were the risk factors for SCA in patients with STEMI. CONCLUSIONS: Left main CAD, lower eGFR, and younger age are the risk factors for cardiac arrest in patients with acute myocardial infarction.
Subject(s)
Heart Arrest , Myocardial Infarction , ST Elevation Myocardial Infarction , Humans , ST Elevation Myocardial Infarction/complications , ST Elevation Myocardial Infarction/diagnostic imaging , ST Elevation Myocardial Infarction/epidemiology , Retrospective Studies , Death, Sudden, Cardiac/epidemiology , Death, Sudden, Cardiac/etiology , Risk Factors , Heart Arrest/complications , Myocardial Infarction/complications , Myocardial Infarction/epidemiology , Treatment OutcomeABSTRACT
Heavy metals and pesticides (HMPs) are common contaminants due to their extensive use worldwide. Diffusive gradients in thin films (DGT) are a good method for measuring the bioavailable concentration of pollutants. This study represents the first evaluation of HMP toxicity in aquatic biota using the DGT technique in sediments. Zhelin Bay was selected as the case study site because it has been contaminated by pollutants. Nonmetric multidimensional scaling (NMS) analysis reveals that a diverse range of pollutants (V, Cr, Ni, Cu, Zn, As, Se, InHg, Mo, Cd, Sb, W, Pb, CLP, PYR) are mainly influenced by sediment characteristics. Assessment of single HMP toxicity found that the risk quotient (RQ) values for Mn, Cu, inorganic Hg (InHg), chlorpyrifos (CLP) and diuron (DIU) are significantly higher than 1, indicating that the adverse effects of these single HMPs should not be ignored. The combined toxicity of HMP mixtures based on probabilistic ecotoxicological risk assessment shows that Zhelin Bay surface sediments had a medium probability (54.6%) of toxic effects to aquatic biota.
Subject(s)
Chlorpyrifos , Mercury , Metals, Heavy , Pesticides , Water Pollutants, Chemical , Biota , Cadmium/analysis , China , Diuron/analysis , Environmental Monitoring/methods , Geologic Sediments/analysis , Isoniazid/analogs & derivatives , Lead/analysis , Mercury/analysis , Metals, Heavy/analysis , Pesticides/analysis , Risk Assessment , Water Pollutants, Chemical/analysisABSTRACT
BACKGROUND: The prognostic significance of conversion into a shockable rhythm in patients who experienced out-of-hospital cardiac arrest (OHCA) with an initially nonshockable rhythm is controversial, perhaps due to the timing of rhythm conversion not being considered previously. We aimed to compare the different prognoses of patients with OHCA and early and late conversion of their rhythm into a shockable rhythm. METHODS: This was a single-centre retrospective cohort study. We enrolled patients with OHCA who were sent to a medical centre in central Taiwan from 2016 to 2020. Patients <18 years old, those with cardiac arrest due to trauma or a circumstantial cause, and those for whom resuscitation was not attempted were excluded. Patients were divided into two groups in accordance with presentation with an initially shockable rhythm. Those with an initially nonshockable rhythm were divided into three subgroups: early-conversion, late-conversion, and nonconversion groups. The primary outcome was the neurological functional status upon discharge from hospital. RESULTS: A total of 1645 patients with OHCA were included: initially shockable rhythm group, 339; early conversion group, 68; late-conversion group, 166; and nonconversion group, 1072. After adjustment, multivariate logistic regression revealed that a favourable neurological outcome was more common in the early conversion group than the nonconversion group (odds ratio [OR] 2.4; 95% confidence interval [CI], 1.1-5.3; p = 0.035), whereas the late-conversion group did not significantly differ from the nonconversion group (OR 0.5; 95% CI, 0.1-1.5; p = 0.211). The proportions of sustained return of spontaneous circulation and survival to discharge were also higher in the early conversion group than the late-conversion group (OR 2.9 95% CI 1.6-5.5, p = 0.001 and OR 4.5, 1.8-11.0, p = 0.001, respectively). CONCLUSION: In patients who experience OHCA and have an initially nonshockable rhythm, early conversion into a shockable rhythm resulted in a better prognosis, whereas late conversion was not significantly different from nonconversion.
Subject(s)
Cardiopulmonary Resuscitation , Emergency Medical Services , Out-of-Hospital Cardiac Arrest , Humans , Adolescent , Cardiopulmonary Resuscitation/methods , Prognosis , Retrospective Studies , Electric Countershock/methods , Emergency Medical Services/methods , RegistriesABSTRACT
Parkinson's disease (PD) is the second most common age-related neurodegenerative disorder with limited clinical treatments. The occurrence of PD includes both genetic and environmental toxins, such as the pesticides paraquat (PQ), as major contributors to PD pathology in both invertebrate and mammalian models. Calycosin, an isoflavone phytoestrogen, has multiple pharmacological properties, including neuroprotective activity. However, the paucity of information regarding the neuroprotective potential of calycosin on PQ-induced neurodegeneration led us to explore whether calycosin can mitigate PD-like phenotypes and the underlying molecular mechanisms. We used a PQ-induced PD model in Drosophila as a cost-effective in vivo screening platform to investigate the neuroprotective efficacy of natural compounds on PD. We reported that calycosin shows a protective role in preventing dopaminergic (DA) neuronal cell death in PQ-exposed Canton S flies. Calycosin-fed PQ-exposed flies exhibit significant resistance against PQ-induced mortality and locomotor deficits in terms of reduced oxidative stress, loss of DA neurons, the depletion of dopamine content, and phosphorylated JNK-caspase-3 levels. Additionally, mechanistic studies show that calycosin administration improves PQ-induced mitochondrial dysfunction and stimulates mitophagy and general autophagy with reduced pS6K and p4EBP1 levels, suggestive of a maintained energy balance between anabolic and catabolic processes, resulting in the inhibition of neuronal cell death. Collectively, this study substantiates the protective effect of calycosin against PQ-induced neurodegeneration by improving DA neurons' survival and reducing apoptosis, likely via autophagy induction, and it is implicated as a novel therapeutic application against toxin-induced PD pathogenesis.
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ABSTRACT: Hepatocellular carcinoma (HCC) is the sixth most common cancer globally, and liver is one of the most commonly injured organs after blunt abdominal trauma. The traumatic liver injury-HCC risk relationship remains unclear.We extracted data of patients with traumatic liver injury between 2000 and 2013 from Taiwan National Health Insurance Research Database (nâ=â15,966) and those of age-, gender-, occupation-, and index year-matched individuals without traumatic liver injury from the general population (nâ=â63,864). Cox proportional hazard models were employed to determine the hazard ratios (HRs) and 95% confidence intervals (CIs) for HCC occurrence in the traumatic liver injury cohort compared with that in the comparison cohort.Patients with traumatic liver injury had an increased HCC risk (adjusted HR 2.13, 95% CI 1.59-2.85); this increased risk was more pronounced within 1âyear after injury (adjusted HR 8.84, 95% CI 4.29-18.2). After >1âyear of injury, HCC risk remained 1.53-fold higher in patients with traumatic liver injury than in those without traumatic liver injury (95% CI 1.08-2.15).People with traumatic liver injury demonstrate a high HCC risk, particularly within the first year of the injury.
Subject(s)
Carcinoma, Hepatocellular/epidemiology , Liver Neoplasms/epidemiology , Liver/injuries , Adult , Aged , Aged, 80 and over , Carcinoma, Hepatocellular/etiology , Female , Humans , Liver Cirrhosis , Male , Middle Aged , Proportional Hazards Models , Risk Factors , Risk ManagementABSTRACT
The aim of this study is to identify potential biomarkers for early diagnosis of gynecologic cancer in order to improve survival. Cervical cancer (CC) and endometrial cancer (EC) are the most common malignant tumors of gynecologic cancer among women in the world. As the underlying molecular mechanisms in both cervical and endometrial cancer remain unclear, a comprehensive and systematic bioinformatics analysis is required. In our study, gene expression profiles of GSE9750, GES7803, GES63514, GES17025, GES115810, and GES36389 downloaded from Gene Expression Omnibus (GEO) were utilized to analyze differential gene expression between cancer and normal tissues. A total of 78 differentially expressed genes (DEGs) common to CC and EC were identified to perform the functional enrichment analyses, including gene ontology and pathway analysis. KEGG pathway analysis of 78 DEGs indicated that three main types of pathway participate in the mechanism of gynecologic cancer such as drug metabolism, signal transduction, and tumorigenesis and development. Furthermore, 20 diagnostic signatures were confirmed using the least absolute shrink and selection operator (LASSO) regression with 10-fold cross validation. Finally, we used the GEPIA2 online tool to verify the expression of 20 genes selected by the LASSO regression model. Among them, the expression of PAMR1 and SLC24A3 in tumor tissues was downregulated significantly compared to the normal tissue, and found to be statistically significant in survival rates between the CC and EC of patients (p < 0.05). The two genes have their function: (1.) PAMR1 is a tumor suppressor gene, and many studies have proven that overexpression of the gene markedly suppresses cell growth, especially in breast cancer and polycystic ovary syndrome; (2.) SLC24A3 is a sodium-calcium regulator of cells, and high SLC24A3 levels are associated with poor prognosis. In our study, the gene signatures can be used to predict CC and EC prognosis, which could provide novel clinical evidence to serve as a potential biomarker for future diagnosis and treatment.
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Bone is the common extra-hepatic site for cancer metastasis. Hepatic cancer is associated with a higher incidence of pathological fracture. However, this important regulatory mechanism remains unexplored. Thus, exosome-mediated cell-cell communication between hepatocellular cancer and bone might be key to osteolytic bone destruction. Huh-7 exosomes were characterized for size and exosome marker expressions (CD63, Alix). Exosome mediated osteoclast differentiation in the RAW 264.7 cells was monitored from day 1 to 6 and multinucleated osteoclast formation and bone resorption activity were analyzed. The osteoclastogenic factor expressions in the exosomes and osteoclast differentiation markers such as tumor necrosis factor receptor 6 (TRAF6), nuclear factor κB (NF-κB), nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1), and cathepsin K (CTSK) were analyzed using western blot. Exosomes released by liver cancer cells (Huh-7) promoted osteoclast differentiation in RAW 264.7 cells. Analysis of osteoclastogenic factors in the exosomes showed that exosomes were specifically enriched with tumor necrosis factor α (TNF-α). Huh-7 exosomes promoted osteoclast differentiation by significantly increasing the number of TRAP-positive multi nucleated osteoclasts and resorption pits. Importantly, exosomes upregulated osteoclast markers TRAF6, NF-κB, and CTSK expressions. Further, neutralizing exosomal TNF-α reverted exosome-mediated osteoclast differentiation in RAW 264.7 cells. Collectively, our findings show that cellular communication of exosomal TNF-α from hepatocellular cancer cells (Huh-7) regulates osteoclast differentiation through NF-κB/CTSK/TRAP expressions. Thus, exosomal TNF-α might act as an important therapeutic target to prevent hepatocellular cancer mediated pathological bone disease.
Subject(s)
Cell Differentiation/physiology , Exosomes/metabolism , Liver Neoplasms/pathology , Osteoclasts/cytology , Tumor Necrosis Factor-alpha/metabolism , Animals , Cathepsin K/metabolism , Culture Media, Conditioned/pharmacology , Exosomes/pathology , Humans , Mice , NF-kappa B/metabolism , RAW 264.7 Cells , Tartrate-Resistant Acid Phosphatase/metabolism , Tumor Necrosis Factor-alpha/pharmacologyABSTRACT
BACKGROUND: Emergency medical service (EMS) personnel have high COVID-19 risk during resuscitation. The resuscitation protocol for patients with out-of-hospital cardiac arrest (OHCA) was modified in response to the COVID-19 pandemic. However, how the adjustments in the EMS system affected patients with OHCA remains unclear. METHODS: We analysed data from the Taichung OHCA registry system. We compared OHCA outcomes and rescue records for 622 cases during the COVID-19 outbreak period (1 February to 30 April 2020) with those recorded for 570 cases during the same period in 2019. RESULTS: The two periods did not differ significantly with respect to patient age, patient sex, the presence of witnesses or OHCA location. Bystander cardiopulmonary resuscitation and defibrillation with automated external defibrillators were more common in 2020 (52.81% vs 65.76%, p<0.001%, and 23.51% vs 31.67%, p=0.001, respectively). The EMS response time was longer during the COVID-19 pandemic (445.8±210.2 s in 2020 vs 389.7±201.8 s in 2019, p<0.001). The rate of prehospital return of spontaneous circulation was lower in 2020 (6.49% vs 2.57%, p=0.001); 2019 and 2020 had similar rates of survival discharge (5.96% vs 4.98%). However, significantly fewer cases had favourable neurological function in 2020 (4.21% vs 2.09%, p=0.035). CONCLUSION: EMS response time for patients with OHCA was prolonged during the COVID-19 pandemic. Early advanced life support by EMS personnel remains crucial for patients with OHCA.
Subject(s)
COVID-19/transmission , Cardiopulmonary Resuscitation/statistics & numerical data , Emergency Medical Services/statistics & numerical data , Infectious Disease Transmission, Patient-to-Professional/prevention & control , Out-of-Hospital Cardiac Arrest/therapy , Adult , Aged , Aged, 80 and over , COVID-19/complications , COVID-19/epidemiology , COVID-19/virology , Cardiopulmonary Resuscitation/standards , Emergency Medical Services/standards , Emergency Medical Technicians/standards , Emergency Medical Technicians/statistics & numerical data , Female , Humans , Male , Middle Aged , Out-of-Hospital Cardiac Arrest/complications , Out-of-Hospital Cardiac Arrest/epidemiology , Pandemics/prevention & control , Practice Guidelines as Topic , Registries/statistics & numerical data , Retrospective Studies , SARS-CoV-2/pathogenicity , Taiwan/epidemiology , Time-to-Treatment/standards , Time-to-Treatment/statistics & numerical data , Young AdultABSTRACT
BACKGROUND: Dual antiplatelet therapy (DAPT) is a standard treatment in non-ST-segment-elevation myocardial infarction (NSTEMI). However, the timing of initiation of DAPT in the Emergency Department (ED) is not well established. The purpose of this study is to demonstrate the correlation between the different timings of DAPT initiation in ED and the outcomes in patients with NSTEMI. METHOD: We retrospectively collected data of patients who were diagnosed as NSTEMI in the ED of China Medical University Hospital during 2016 to 2019. All NSTEMI patients who required coronary stenting or ballooning were enrolled into the study, which means NSTEMI patients who received percutaneous coronary intervention (PCI) were included. The time interval between ED arrival and DAPT given was recorded. Patients were divided into 2 groups according to whether they received DAPT within 6 hours after arrival to the ED. The primary outcomes were in-hospital major adverse cardiovascular events (MACE). The secondary outcomes were unexpected return to the ED within 72 hours, readmission within 14 days, and revascularization procedures performed within the first 30 days. RESULTS: 938 NSTEMI patients with PCI were enrolled. Patients who received DAPT beyond 6 hours were relatively old (65.70 ± 14.13 versus 63.16 ± 13.31, p=0.014) and had relatively more comorbidities and higher Killip scores than those who received DAPT within 6 hours. The group that received DAPT within 6 hours had lower in-hospital MACE rate (3.52% versus 8.37%, p=0.009). Multivariate logistic regression showed the group beyond 6 hours was independently associated with higher risk for in-hospital MACE rate (OR : 2.09, 95% CI 1.07-4.07, p=0.030). CONCLUSION: Among patients with NSTEMI, DAPT beyond 6 hours after ED arrival have higher in-hospital MACE rate than those within 6 hours.
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ABSTRACT: Metabolic acidosis is observed in 98% of patients with out-of-hospital cardiac arrest (OHCA). The longer the no-flow or low-flow duration, the more severe is the acidosis in these patients. This study explored whether blood pH in early stages of advanced life support (ALS) was an independent predictor of neurological prognosis in patients with OHCA.We retrospectively enrolled patients with OHCA from January 2012 to June 2018 in a single-medical tertiary hospital in Taiwan. Patients with OHCA whose blood gas analyses within 5âminutes after receiving ALS at the emergency department (ED) were enrolled. Patients younger than 20âyears old, with cardiac arrest resulting from traumatic or circumstantial causes, with return of spontaneous circulation (ROSC) before ED arrival, lacking record of initial blood gas analysis, and with do-not-resuscitate orders were excluded. The primary outcome of this study was neurological status at hospital discharge.In total, 2034 patients with OHCA were enrolled. The majority were male (61.89%), and the average age was 67.8â±â17.0âyears. Witnessed OHCA was noted in 571 cases, cardiopulmonary resuscitation was performed before paramedic arrival in 512 (25.2%) cases, and a shockable rhythm was observed in 269 (13.2%). Blood pH from initial blood gas analysis remained an independent predictor of neurological outcome after multivariate regression.Blood pH at early stages of ALS was an independent prognostic factor of post-OHCA neurological outcome. Blood gas analysis on arrival at the ED may provide additional information about the prognosis of patients with OHCA.
Subject(s)
Acidosis , Blood Gas Analysis , Cardiopulmonary Resuscitation/methods , Emergency Medical Services , Nervous System Diseases , Out-of-Hospital Cardiac Arrest , Acidosis/diagnosis , Acidosis/etiology , Aged , Blood Gas Analysis/methods , Blood Gas Analysis/statistics & numerical data , Cardiopulmonary Resuscitation/standards , Emergency Medical Services/methods , Emergency Medical Services/statistics & numerical data , Female , Humans , Hydrogen-Ion Concentration , Male , Nervous System Diseases/diagnosis , Nervous System Diseases/epidemiology , Nervous System Diseases/etiology , Neurologic Examination/methods , Neurologic Examination/statistics & numerical data , Out-of-Hospital Cardiac Arrest/blood , Out-of-Hospital Cardiac Arrest/complications , Out-of-Hospital Cardiac Arrest/epidemiology , Out-of-Hospital Cardiac Arrest/therapy , Outcome and Process Assessment, Health Care , Prognosis , Taiwan/epidemiology , Tertiary Care Centers , Time-to-Treatment/statistics & numerical dataABSTRACT
Mitochondrial dysfunction contributes to the pathophysiology of acute kidney injury (AKI). Mitophagy selectively degrades damaged mitochondria and thereby regulates cellular homeostasis. RNA-binding proteins (RBPs) regulate RNA processing at multiple levels and thereby control cellular function. In this study, we aimed to understand the role of human antigen R (HuR) in hypoxia-induced mitophagy process in the renal tubular cells. Mitophagy marker expressions (PARKIN, p-PARKIN, PINK1, BNIP3L, BNIP3, LC3) were determined by western blot analysis. Immunofluorescence studies were performed to analyze mitophagosome, mitolysosome, co-localization of p-PARKIN/TOMM20 and BNIP3L/TOMM20. HuR-mediated regulation of PARKIN/BNIP3L expressions was determined by RNA-immunoprecipitation analysis and RNA stability experiments. Hypoxia induced mitochondrial dysfunction by increased ROS, decline in membrane potential and activated mitophagy through up-regulated PARKIN, PINK1, BNIP3 and BNIP3L expressions. HuR knockdown studies revealed that HuR regulates hypoxia-induced mitophagosome and mitolysosome formation. HuR was significantly bound to PARKIN and BNIP3L mRNA under hypoxia and thereby up-regulated their expressions through mRNA stability. Altogether, our data highlight the importance of HuR in mitophagy regulation through up-regulating PARKIN/BNIP3L expressions in renal tubular cells.
Subject(s)
ELAV-Like Protein 1/metabolism , Epithelial Cells/metabolism , Hypoxia/genetics , Hypoxia/metabolism , Membrane Proteins/genetics , Mitophagy/genetics , Proto-Oncogene Proteins/genetics , Tumor Suppressor Proteins/genetics , Ubiquitin-Protein Ligases/genetics , Acute Kidney Injury/etiology , Acute Kidney Injury/metabolism , Acute Kidney Injury/pathology , Cell Line, Tumor , Gene Expression , Gene Knockdown Techniques , Humans , Kidney Tubules , Lysosomes/metabolism , Mitochondria/genetics , Mitochondria/metabolism , Models, Biological , Phagosomes/metabolismABSTRACT
Background: Whether there is a difference in prognosis between elderly patients with ST-elevation myocardial infarction (STEMI) and non-ST-elevation myocardial infarction (NSTEMI) remains mysterious. Methods: We conducted a retrospective cohort study by analyzing the data in the Longitudinal Health Insurance Database (LHID) in Taiwan to explore differences between STEMI and NSTEMI with respect to in-hospital and long-term (3-year) outcomes among older adult patients (aged ≥65 years). Patients were further stratified based on whether they received coronary revascularization. Results: In total, 5,902 patients aged ≥65 years with acute myocardial infarction (AMI) who underwent revascularization (2,254) or medical therapy alone (3,648) were included. In the revascularized group, no difference was observed in cardiovascular (CV) and all-cause mortality during hospitalization or at 3-year follow-up between the two AMIs. Conversely, in the non-revascularized group, patients with NSTEMI had higher crude odds ratio (cOR) for all-cause death during hospitalization [cOR: 1.33, 95% confidence interval (CI) = 1.07-1.65] and at 3-year follow-up (cOR: 1.47, 95% CI = 1.21-1.91) relative to patients with STEMI. However, after multivariable adjustments, only NSTEMI indicated fewer in-hospital CV death [adjusted odds ratio (aOR): 0.75, 95% CI = 0.58-0.98] than STEMI in non-revascularized group. Moreover, major bleeding was not different between patients with STEMI or NSTEMI aged ≥65 years old. Conclusion: Classification of AMI is not associated with the difference of in-hospital or 3-year CV and all-cause death in older adult patients received revascularization. In a 3-year follow-up period, STEMI was an independent predictor of a higher incidence of revascularization after the index event. Non-ST-elevation myocardial infarction had more incidence of MACE than patients with STEMI did in both treatment groups.
ABSTRACT
METHODS: Patients with out-of-hospital cardiac arrest (OHCA) were prospectively registered in Taichung. The 29 districts of Taichung city were divided into urban and rural areas based on whether the population density is more than 1,000 people per square kilometer. Prehospital data were collected according to the Utstein-style template, and telephone auditory records were collected by a dispatch center. RESULTS: 2,716 patients were enrolled during the study period. 88.4% OHCA occurred in urban areas and 11.6% in rural areas. 74.9% after dispatcher assistance, laypersons performed CPR in urban areas and 67.7% in rural areas (p=0.023). The proportion of laypersons continued CPR until an emergency medical technician's (EMT) arrival was higher in the urban areas (59.57% vs 52.27%, p=0.039). Laypersons continued CPR until an EMT' arrival would increase the chance of return of spontaneous circulation in urban and rural areas, with adjusted odds ratio (aOR) of 1.02, 95% confidence interval (CI) of 0.82-1.27, and aOR of 1.49, 95% CI of 0.80-2.80, respectively. Continued laypersons CPR until the EMT' arrival also improved survival with favorable neurological function, with aOR of 1.16, 95% CI of 0.61-2.20 in urban areas and aOR of 2.90 95% CI of 0.18-46.81 in rural areas. CONCLUSION: Bystanders in urban areas exhibited higher ratio of acceptance of DACPR. However, after DACPR intervention, prognosis improvement was considerably higher in rural areas than in urban areas.
ABSTRACT
Autophagy, an important cellular homeostatic mechanism regulates cell survival under stress and protects against acute kidney injury. However, the role of long noncoding RNA (lncRNA) in autophagy regulation in renal tubular cells (HK-2) is unclear. The study was aimed to understand the importance of lncRNA in hypoxia-induced autophagy in HK-2 cells. LncRNA eosinophil granule ontogeny transcript (EGOT) was identified as autophagy-associated lncRNA under hypoxia. The lncRNA EGOT expression was significantly downregulated in renal tubular cells during hypoxia-induced autophagy. Gain- and loss-of-EGOT functional studies revealed that EGOT overexpression reduced autophagy by downregulation of ATG7, ATG16L1, LC3II expressions and LC 3 puncta while EGOT knockdown reversed the suppression of autophagy. Importantly, RNA-binding protein, (ELAVL1)/Hu antigen R (HuR) binds and stabilizes the EGOT expression under normoxia and ATG7/16L1 expressions under hypoxia. Furthermore, HuR mediated stabilization of ATG7/16L1 expressions under hypoxia causes a decline in EGOT levels and thereby promotes autophagy. Altogether, the study first reveals the functional interplay of lncRNA EGOT and HuR on the posttranscriptional regulation of the ATG7/16L1 expressions. Thus, the HuR/EGOT/ATG7/16L1 axis is crucial for hypoxia-induced autophagy in renal tubular cells.
Subject(s)
Autophagy , ELAV-Like Protein 1/metabolism , Hypoxia/physiopathology , Kidney Tubules/pathology , RNA, Long Noncoding/genetics , Cell Proliferation , Cells, Cultured , ELAV-Like Protein 1/genetics , Humans , Kidney Tubules/metabolismABSTRACT
Primary percutaneous coronary intervention (PPCI) is the preferred treatment method for ST-segment elevation myocardial infarction (STEMI). Many efforts had been made to reduce door-to-balloon (DTB) time in patients with STEMI. The objective of this study is to demonstrate how intrahospital social media communication reduced DTB times in STEMI patients requiring an interhospital transfer.We retrospectively enrolled patients with STEMI who had been transferred from other hospitals during 2016 and 2017. Patients were divided into 2 groups. The previewed group had an electrocardiogram (ECG) done at the first hospital that was previewed by the cardiologist via social media. The control group was treated using the conventional clinical approach. We compared DTB time and outcome between 2 groups.The 2 groups shared some similar clinical characteristics. However, the previewed group had significantly shorter DTB times than the control group (nâ=â51, DTB 52.61â±â42.20 vs nâ=â89, DTB time 78.40â±â50.64, Pâ=â.003). The time elapsed between ECG and the call to the laboratory decreased most apparently in the previewed group (-11.24â±â48.81 vs 16.96â±â33.08, Pâ<â.001). The previewed group also tended to have less in-hospital major adverse cardiovascular events (Pâ=â.091).When the patients with STEMI required transfer to the PCI-capable hospital, using social media to preview ECG reduced DTB time, mainly because the cardiologists activated the catheter laboratories much earlier, sometimes even before the patients arrived at the PCI-capable hospital.